CN1240210A - Substituted tricyclic compound - Google Patents
Substituted tricyclic compound Download PDFInfo
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- CN1240210A CN1240210A CN99107687A CN99107687A CN1240210A CN 1240210 A CN1240210 A CN 1240210A CN 99107687 A CN99107687 A CN 99107687A CN 99107687 A CN99107687 A CN 99107687A CN 1240210 A CN1240210 A CN 1240210A
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- methyl
- phenyl
- carbazole
- carbamoyl
- carbazol
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
Novel tricyclics are disclosed together with the use of such compounds for inhibiting sPLA2 mediated release of fatty acids for treatment of conditions such as septic shock.
Description
The present invention relates to new replacement three ring organic compound, they can be used for suppressing sPLA under disease (for example septic shock) condition
2The lipid acid of mediation discharges.
The phospholipase A of human non-pancreatic secretion
2(below be called " sPLA
2") structure and physical properties in two pieces of articles, done sufficient description, i.e. Seilhamer, Jeffrey J.; Pruzanski, Waldemar; VadasPeter; Plant, Shelley; Miller, Judy A; Kloss, Jean; And Johnson, Lorin K. is published in The Journal of Bioloical Chemistry, Vol.264, No.10, April 5 published, " clone and the recombinant chou that are present in the Phospholipase A2 in the rheumatic arthritis synovia are expressed " and Kramer on the pp5335-5336 (1989), Ruth M; Heission, Catherine; Johansen, Berit; Hayes, Gretchen; McGray, Paula; Chow, E.Pingchang; Tizard, Richard; And Pepinsky, R.Blake is published in The Journal of Biological Chemistry, Vol.264, and No.10, April 5 published, " structure of human non-pancreatic phospholipase A2 and the character " on the pp5768-5775 (1989).The content of these two pieces of documents is all incorporated this paper into for referencial use at this.
It is believed that sPLA
2It is a kind of rate-limiting enzyme in the arachidonic acid cascade of hydrolysis membrane phospholipid.Therefore, exploitation can suppress sPLA
2The compound that the lipid acid (for example arachidonic acid) of mediation discharges is very important.These compounds will be used to treatment by sPLA
2The overexpression disease of inducing and/or keeping for example shock that causes of septic shock, adult respiratory distress syndrome, pancreatitis, wound, bronchial asthma, allergic rhinitis, rheumatoid arthritis etc.
Wish to develop the new sPLA that is used for the treatment of
2The compound of the disease that causes and therapy.
People's such as Alexander U.S.P.3,939,177 and U.S.P.3,979,391 disclose and can be used as 1,2,3 of sterilant, the 4-tetrahydro carbazole.
The invention provides the tricyclic compound shown in the following general formula (I) or its pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or salt:
Wherein: Z is a cyclohexenyl, or phenyl, R
20Be selected from group (a), (b) and (c), wherein:
(a) be-(C5-C20) alkyl ,-(C5-C20) alkenyl ,-(C5-C20) alkynyl group, carbocylic radical, or heterocyclic radical, or
(b) be by group among one or more independent (a) that substituting group replaced of not interfering with each other that select; Or
(c) be group-(L)-R
80Wherein, (L)-for containing 1-12 divalent linker that is selected from carbon, hydrogen, oxygen, nitrogen and sulphur atom; Wherein-(L)-and the combination of middle atom is selected from (i) and has only carbon and hydrogen, (ii) has only a sulphur, (iii) has only an oxygen, (iv) has only one or two nitrogen and hydrogen, and (v) have only carbon, hydrogen and a sulphur and (vi) have only carbon, hydrogen and oxygen; And R wherein
80For being selected from (a) or group (b); R
21Be the substituting group that does not interfere with each other, wherein f is 1-3; R
1For-NHNH
2,-NH
2, or-CONH
2R
2 'Be selected from group-OH and-O (CH
2)
tR
5 ', wherein
R
5 'Be H ,-CN ,-NH
2,-CONH
2,-CONR
9R
10,-NHSO
2R
15-CONHSO
2R
15, R wherein
15For-(C
1-C
6) alkyl or-CF
3Phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that replaces of alkyl; With-(L
a)-(acidic-group), wherein-(L
a)-for the acid with 1-7 basic length of acid connection connects base, and t is 1-5; R
3 'Be selected from the substituting group that does not interfere with each other, carbocylic radical, the carbocylic radical that substituting group replaced that is not interfered with each other, heterocyclic radical and the heterocyclic radical that substituting group replaced that is not interfered with each other.
These replace tricyclic compound can suppress people sPLA effectively
2The lipid acid of mediation discharges.
The invention still further relates to pharmaceutical preparation, it contains formula I compound and one or more pharmaceutically acceptable diluents, carrier and excipient.
The invention still further relates to and suppress sPLA
2Method, this method comprises the formula I compound to the administration of this treatment of needs treatment significant quantity.
Another aspect of the present invention has provided selectivity inhibition sPLA in the Mammals of this treatment of needs
2Method, this method comprises the formula I compound to described administration treatment significant quantity.
The present invention also further provides the formula I compound that is used as medicine in the following disease of treatment: diseases associated with inflammation such as septic shock, adult respiratory distress syndrome, pancreatitis, suffer a shock due to the wound, bronchial asthma, rhinallergosis, rheumatoid arthritis, cystic fibrosis of the pancreas, apoplexy, acute bronchitis, chronic bronchitis, acute bronchiolitis, chronic bronchiolitis, osteoarthritis, gout, arthritis vertebralis, ankylosing spondylitis, Josef Reiter disease syndrome, arthropathia psoriatica, the vertebra inflammatory bowel, teenager's property joint disease, or teenager's property ankylosing spondylitis, reactive arthropathy, infective arthritis or infection posterior joint inflammation, gonococcal arthiritis, tuberculous arthritis, viral arthritis, arthritis fungosa, syphilitic arthritis, Lyme disease, with " vascular inflammatory syndromes " relevant sacroiliitis, the nodositas polyarthritis, allergic angiitis, Luegenec granulomatosis, polymyalgia rheumatica, joint cell arteritis, calcium crystallization deposition joint disease, pseudogout, nonarticular rheumatism, bursitis, tenosynovitis goes up (condyle) scorching (tennis elbow), carpal tunnel syndrome, reusability damage (typewriting), various forms of sacroiliitis, neuropathy is because of property joint disease (neurogenic arthrosis), hemarthrosis, Heng Nuohe-She Enlaiyin (Henoch-Schonlein) purpura, hpertrophic osteoarthropathy, multicentric reticulohistiocytosis, the sacroiliitis relevant with some disease, surcoilosis, hemochromatosis, reaping hook cytopathy and other hemoglobinopathy, hyperlipoproteinemia disease, hypogammaglobulinemia disease, hyperparathyroidism, acromegaly, familial Mediterranean fever, the Behat disease, systemic lupus erythematous, or relapsing polychondritis and relative disease.Its methods of treatment comprises that this consumption is enough to suppress sPLA to the formula I compound of the administration treatment significant quantity of this treatment of needs
2Thereby the lipid acid of mediation discharges and suppresses or prevent the formation of arachidonic acid cascade and harmful product thereof.
In addition, the present invention also provides preparation formula II compound or its pharmaceutically useful racemic modification, solvate, and tautomer, optically active isomer, the method for prodrug derivant or salt:
Wherein: Z is a cyclohexenyl, or phenyl, R
21Be the substituting group that does not interfere with each other; R
1For-NHNH
2Or-NH
2R
2Be selected from group-OH and-O (CH
2)
mR
5, wherein
R
5Be H ,-CO
2H ,-CONH
2,-CO
2(C
1-C
4Alkyl);
, R wherein
6And R
7Be independently of one another-OH or-O (C
1-C
4) alkyl;-SO
3H ,-SO
3(C
1-C
4Alkyl), tetrazyl ,-CN ,-NH
2,-NHSO
2R
15-CONHSO
2R
15, R wherein
15For-(C
1-C
6) alkyl or-CF
3Phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that alkyl replaces, wherein m is 1-3; R
3Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkenyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-CONH
2,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, or-phenyl-(C
1-C
4) alkyl, and n is 1-8; And R
4Be H ,-(C
5-C
14) alkyl ,-(C
3-C
14) cycloalkyl, pyridyl, phenyl or be selected from the following phenyl that substituting group replaced :-(C by 1-5
1-C
6) alkyl, halogen ,-CF
3,-OCF
3,-(C
1-C
4) alkoxyl group ,-CN ,-(C
1-C
4) alkylthio, phenyl (C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, phenyl, phenoxy group ,-OR
9R wherein
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl or-phenyl (C
1-C
4) alkyl; Tetrazolium; Quilt-(C
1-C
4) alkyl or-(C
1-C
4) tetrazolium that replaces of alkyl phenyl; Or naphthyl;
A) esterification formula XVI compound:
Wherein X is a halogen; Form formula XV compound:
Wherein PG is sour protecting group,
B) reduction-type XV compound formation formula XIV compound:
Wherein PG is sour protecting group,
C) shrinking type XIV compound and formula XIII compound:
R wherein
3 (a)Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkenyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, or-phenyl-(C
1-C
4) alkyl, and n is 1-8; Form formula XII compound:
D) cyclization formula XII compound forms formula XI compound:
E) use formula XCH
2R
4Alkylating agent (wherein X is a halogen) alkylation formula XI compound forms formula X compound:
F) dehydrogenation formula X compound forms formula IX compound:
G) amination formula IX compound forms formula VIII compound:
H) use formula XCH
2R
15(wherein X is a halogen to alkylating agent, and R
15For-CO
2R
16,-SO
3R
16,-P (O) (OR
16)
2, or-P (O) (OR
16) H, wherein R
16Be sour protecting group) alkylation formula VIII compound, form formula VII compound:
I) hydrolyzing type VII compound randomly forms formula I compound, and randomly makes formula I compound salify.
In addition, the present invention also provides preparation formula II compound or its pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, the method for prodrug derivant or salt; The method comprising the steps of:
A) esterification formula XVI compound:
Wherein X is a halogen, forms formula XV compound:
Wherein PG is sour protecting group;
B) shrinking type XV compound and formula XVII compound:
Form formula XVIII compound:
C) cyclisation formula XVIII compound formation formula XIX compound:
D) use formula XCH
2R
4Alkylating agent (wherein X is a halogen) alkylation formula XIX compound forms formula XX compound:
E) dealkylation formula XX compound, production IX compound:
F) amination formula IX compound forms formula VIII compound:
G) use formula XCH
2R
15(wherein X is a halogen to alkylating agent, and R
15For-CO
2R
16,-SO
3R
16, P (O) (OR
16)
2, or-P (O) (OR
16) H, wherein R
16Be sour protecting group) alkylation formula VIII compound, form formula VII compound:
H) hydrolyzing type VII compound randomly forms formula I compound, and randomly makes formula I compound salify.In addition, the present invention also provides new formula III intermediate:
Wherein, PG is sour protecting group; R
21Be the substituting group that does not interfere with each other; R
12Be H or CH
2R
4, R wherein
4Be H ,-(C
5-C
14) alkyl ,-(C
3-C
14) cycloalkyl, pyridyl, phenyl or be selected from the following phenyl that substituting group replaced :-(C by 1-5
1-C
6) alkyl, halogen ,-CF
3,-OCF
3,-(C
1-C
4) alkoxyl group ,-CN ,-(C
1-C
4) alkylthio, phenyl (C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, phenyl, phenoxy group ,-OR
9R wherein
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl or-phenyl (C
1-C
4) alkyl; Tetrazolium; Quilt-(C
1-C
4) alkyl or-(C
1-C
4) tetrazolium that replaces of alkyl phenyl; Or naphthyl; R
3 (a)Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkenyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, or-phenyl (C
1-C
4) alkyl, and n is 1-8; Z is cyclohexenyl or phenyl; With X be halogen.As another embodiment, the invention provides formula IV intermediate:
Wherein, PG is sour protecting group; R
21Be the substituting group that does not interfere with each other; R
12Be H or CH
2R
4, R wherein
4Be H ,-(C
5-C
14) alkyl ,-(C
3-C
14) cycloalkyl, pyridyl, phenyl or be selected from the following phenyl that substituting group replaced :-(C by 1-5
1-C
6) alkyl, halogen ,-CF
3,-OCF
3,-(C
1-C
4) alkoxyl group ,-CN ,-(C
1-C
4) alkylthio, phenyl (C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, phenyl, phenoxy group ,-OR
9R wherein
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl or-phenyl (C
1-C
4) alkyl; Tetrazolium; Quilt-(C
1-C
4) alkyl or-(C
1-C
4) tetrazolium that replaces of alkyl phenyl; Or naphthyl; R
3 (a)Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkenyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, or-phenyl (C
1-C
4) alkyl, and n is 1-8; R
11For-OH ,=O ,-O (C
1-C
4) alkyl or-O (CH
2) R
15, R wherein
15For-CO
2R
16,-SO
3R
16, P (O) (OR
16)
2, or P (O) (OR
16) H, wherein R
16Be sour protecting group; With A and Z be phenyl or cyclohexenyl independently of one another, its condition is that A and Z can not be phenyl.In embodiment further, the invention provides new formula XVIII intermediate:
Wherein PG is sour protecting group; R
21Be the substituting group that does not interfere with each other; R
3 (a)Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkenyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, or-phenyl (C
1-C
4) alkyl, and n is 1-8.
According to subsequently description and additional claim, other purpose of the present invention, aspect and advantage will be conspicuous.Definition
Term used herein " alkyl " itself or as other substituent part, unless otherwise defined, be meant the univalence hydrocarbyl of straight or branched, for example methyl, ethyl, n-propyl, sec.-propyl, normal-butyl, the tertiary butyl, isobutyl-, sec-butyl, n-pentyl, isopentyl, neo-pentyl, heptyl, hexyl, octyl group, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl etc.Term " alkyl " comprises-(C1-C2) alkyl ,-(C1-C4) alkyl ,-(C1-C6) alkyl ,-(C5-C14) alkyl and-(C1-C10) alkyl.
Term used herein " alkenyl " representative has the undersaturated side chain of olefinic or the straight chain group of two keys at least, and the example of this group comprises for example diene and the trialkenyl of vinyl, allyl group, crotyl, 3-butenyl, pentenyl, 3-pentenyl, 4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 2-heptenyl, 3-heptenyl, 4-heptenyl, 5-heptenyl, 6-heptenyl and straight chain and side chain.
The group of term " alkynyl group " representative such as ethynyl, proyl, butynyl, pentynyl, hexin base, heptyne base and diine and three alkynes.
Term " halogen " is meant chlorine, fluorine, bromine or iodine.
The group that term used herein " (C1-C4) alkoxyl group " representative links to each other with the rest part of molecule by Sauerstoffatom such as methoxyl group, oxyethyl group, positive propoxy, n-butoxy, tert.-butoxy etc.
Term " phenyl (C1-C4) alkyl " is meant and contains straight or branched alkyl 1-4 carbon atom, that link to each other with phenyl ring that wherein alkyl chain links to each other with the rest part of molecule.Typical phenylalkyl comprises benzyl, styroyl, phenyl propyl, propyloxy phenyl base and phenyl butyl.
Term " (C1-C4) alkylthio " be defined as contain 1-4 carbon atom, by the straight or branched alkyl that sulphur atom links to each other with the rest part of molecule.Typically-(C1-C4) alkylthio comprises methylthio group, ethylmercapto group, rosickyite base, butylthio etc.
Term " (C3-C14) cycloalkyl " comprises such group for example cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, suberyl, ring octyl group, ring nonyl, ring decyl, ring hendecane base, ring 12 carbon alkyl, ring n-tridecane base, ring n-tetradecane base etc.Term " (C3-C14) cycloalkyl " comprises-(C3-C7) cycloalkyl.
Term " heterocyclic radical " is meant derived from containing 5-14 annular atoms and containing the group that 1-3 is selected from the heteroatomic monocycle of nitrogen, oxygen or sulphur or many rings, saturated or undersaturated, replacement or unsubstituted heteronucleus.Typical heterocyclic radical is a pyridyl, thienyl, fluorenyl, pyrryl, furyl, thienyl, pyrazolyl, imidazolyl, the phenylimidazole base, triazolyl isoxazolyl oxazolyl, thiazolyl, thiadiazolyl group, indyl, carbazyl, the passiflorin base falls, azaindolyl, benzofuryl, dibenzofuran group, thianaphthenyl, the dibenzothiophene base, indazolyl, imidazo [1.2-A] pyridyl, the benzotriazole base, the adjacent first lactam group of benzene, 1,2-benzoisoxazole base benzoxazolyl, benzothiazolyl, purine radicals, pyridyl, bipyridyl, phenylpyridyl, the benzyl-pyridine base, pyrimidyl, the phenyl pyrimidine base, pyrazinyl, 1,3, the 5-triazinyl, quinolyl, the 2 base, quinazolyl is with quinoxalinyl.
Term " carbocylic radical " is meant that wherein the one-tenth annular atoms of organic core (not comprising hydrogen) has only carbon atom derived from the group of saturated or undersaturated, replacement or unsubstituted 5-14 person's organic core.Typical carbocylic radical is the relevant dibenzyl homologue of cycloalkyl, cycloalkenyl group, phenyl, naphthyl, norbornene, bicyclo-heptadiene base, tolyl, xylyl, indenyl, stilbenyl, terphenyl, diphenylacetylene, benzyl ring hexenyl, acenaphthenyl and anthryl, xenyl, dibenzyl and following formula (bb) representative
Wherein n is the integer of 1-8.
Term " substituting group that does not interfere with each other " be meant be adapted at tricyclic ring (shown in formula III) 1,2,3,7 and/or 8 go up the group that replaces and be adapted at the heterocyclic radical of above-mentioned definition and carbocylic radical on the group that replaces.The illustrative group that does not interfere with each other is H;-(C1-C14) alkyl;-(C2-C6) alkenyl;-(C2-C6) alkynyl group;-(C7-C12) aralkyl;-(C7-C12) alkaryl;-(C3-C8) cycloalkyl;-(C3-C8) cycloalkenyl group; phenyl; tolyl; xylyl; xenyl;-(C1-C6) alkoxyl group;-(C2-C6) alkenyloxy;-(C2-C6) alkynyloxy group;-(C1-C12) alkoxyalkyl;-(C1-C12) alkoxyl group alkoxyl group;-(C1-C12) alkyl-carbonyl;-(C1-C12) alkyl-carbonyl-amino;-(C1-C12) alkoxy amino;-(C1-C12) alkoxy amino carbonyl;-(C1-C12) alkylamino;-(1-C6) alkylthio;-(C1-C12) alkylthio carbonyl;-(C1-C6) alkyl sulphinyl;-(C1-C6) alkyl sulphonyl;-(C1-C6) halogenated alkoxy;-(C1-C6) halogenated alkyl sulfonyl;-(C1-C6) haloalkyl;-(C1-C6) hydroxyalkyl;-(CH
2)
nCN ,-(CH
2)
nNR
9R
10,-C (O) O (C1-C6 alkyl) ,-(CH
2)
nO (C1-C6 alkyl), benzyloxy, phenoxy group, thiophenyl ,-(CONHSO
2) R
15(R wherein
15Be-(C1-C6) alkyl) ,-CF
3, naphthyl or-(CH
2)
sPhenyl (wherein s is 0-5) ,-CHO ,-CF
3,-OCF
3, pyridyl, amino, amidino groups, halogen, formamyl, carboxyl, carbalkoxy ,-(CH
2)
nCO
2H, cyano group, cyano group guanidine radicals, guanidine radicals, hydrazide group, diazanyl, hydrazide group, hydroxyl, hydroxyl amino, nitro, phosphono ,-SO
3H-, thioacetal, thiocarbonyl, furyl, thienyl ,-COR
9,-CONR
9R
10,-NR
9R
10,-NCHCOR
9,-SO
2R
9,-OR
9,-SR
9, CH
2SO
2R
9, tetrazyl or quilt-(C
1-C
6) alkyl, phenyl or-(C
1-C
4) tetrazyl that replaces of alkyl phenyl ,-(CH
2)
nOsi (C
1-C
6) alkyl and (C
1-C
6) alkyl-carbonyl, wherein n is 1-8, and R
9And R
10Be independently H ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl or-phenyl (C
1-C
4) alkyl.
An organic group represented in term " acidic-group ", when this organic group by suitable connection atom (being defined as " acid connect base " later on) when linking to each other, as the proton donor that can form hydrogen bond with a tricyclic ring.Representational acidic-group is following:
-CO
2H、
-5-tetrazyl,
-SO
3H,
Wherein n is 1-8, R89 be a kind of metal or-(C
1-C
10) alkyl, and R
99Be H or-(C
1-C
10) alkyl.
Term " acid connect base " be digit symbol be-(La)-divalent linker, its effect is according to following universal relation 5 or 6 of tricyclic ring to be coupled together with an acidic-group:
(tricyclic ring)-(La)-acidic-group
Term " acid connect basic length " be meant connect 5 or 6 of tricyclic ring with the linking group of acidic-group-(La)-in the shortest intrachain atom number (not comprising hydrogen).-(La)-carbocyclic ring of middle existence can be regarded as and the roughly suitable atom number of isocyclic diameter that calculates.Therefore, calculating-(La)-length the time, phenyl ring or cyclohexane ring that acid connects in the base be can be regarded as 2 atoms.Illustrative acid connects base and comprises:
Wherein t is 1-5, and Q is selected from group-(CH
2)-,-O-,-NH-and-S-, and R
84And R
85Be selected from independently of one another H ,-(C
1-C
10) alkyl, aryl ,-(C
1-C
10) alkylaryl ,-(C
1-C
10) arylalkyl, carboxyl, carbalkoxy and halogen, when t was one (1), it was respectively 3,3,2 and 2 that the acid of group (a) and (b), (c) and (d) is connected basic length.
Above-mentioned trinucleated salt is another aspect of the present invention.Have in the example of acidic functionality at those compounds wherein of the present invention, can form various more soluble in water than parent compound, be more suitable for the salt that physiology uses.Representative pharmaceutically acceptable salt includes but not limited to basic metal and alkaline earth salt, for example lithium salts, sodium salt, sylvite, calcium salt, magnesium salts, aluminium salt etc.Conventional by in solution, preparing salt with alkaline purification acid or by making acid contact the cause free acid with a kind of ion exchange resin.
Be included in the definition of acceptable salt pharmaceutically is the nontoxic relatively organic and mineral alkali additive salt of The compounds of this invention, for example ammonium salt, quaternary ammonium salt and derive the amine positively charged ion that obtains (for example referring to people such as S.M.Berge from nitrogenous base with enough alkalescence and compound formation salt of the present invention, " pharmaceutical salts ", J.Phar.Sci, 66:1-19 (1977)).
Compound of the present invention can have chiral centre and exist with optically active bodily form formula, and R-and S-isomer and raceme mixture all are that the present invention considers.By known method, use contains asymmetric center and the raw material that split carries out the stereospecificity reaction, can prepare specific steric isomer, in addition, use known method that stereoisomer mixture is reacted the back fractionation and also can prepare specific steric isomer.
Prodrug is the derivative of The compounds of this invention, and it contains and can become the The compounds of this invention that has pharmacologically active in vivo by chemical reaction or metabolism cracked group and by solvolysis or under physiological condition.The bronsted lowry acids and bases bronsted lowry derivative form of the derivative of The compounds of this invention all has activity, but its acid derivative form usually has advantage (referring to Bundgard aspect solvability, histocompatibility or the delay release in the mammals organism, H.Design of Prodrugs, pp.7-9,21-24, Elsevier, Amsterdam 1985).Prodrug comprises acid derivative, for example by making ester that parent acd compound and the reaction of a kind of suitable alcohol make or by making parent acd compound and a kind of suitable amine react the acid amides that makes.From loading on that carboxyl on the compound of the present invention is derived and the aliphatic hydrocarbon ester (for example methyl, ethyl, propyl group, sec.-propyl, butyl, sec-butyl, tertiary butyl ester) or the aromatic hydrocarbon ester that obtain are preferred prodrugs.Other preferred ester comprises morpholinyl oxyethyl group, Diethylene Glycol acid amides and diethylamino carbonyl methoxyl group ester.In some cases, need the prodrug of preparation diester-type, for example (acetoxyl group) alkyl ester or ((alkoxy carbonyl) oxygen base) alkyl ester.
Commonly used the same in term used herein " acid protecting group " and the synthetic organic chemistry; be meant a kind of prevent when in some other functional groups of molecule, reacting acidic group participate in reaction, but the group that when needs are removed, can remove again; T.W.Greene is at Protective Groups in Organic Synthesis; John Wiley and Sons; New York; 1981 the 5th chapter has been discussed such group, and the content of the document is all incorporated this paper into for referencial use at this.The example of acid protecting group comprises the ester or the amide derivatives of acidic group; for example methyl, methoxymethyl, methylthiomethyl, THP trtrahydropyranyl, methoxy ethoxy methyl, benzyloxymethyl, phenyl, aryl, ethyl, 2; 2; 2-three chloroethyls, 2-methylmercaptoethyl, the tertiary butyl, cyclopentyl, trityl group, diphenyl methyl, benzyl, trimethyl silyl, N, N-dimethyl, pyrrolidyl, piperidyl or adjacent p-nitroanilide.Preferred acid protecting group is a methyl.Preferred several groups formulas (I) compound:
The compound of one group formula (I) is R wherein
21Select white H, halogen ,-(C
1-C
3) alkyl ,-(C
3-C
4) cycloalkyl ,-(C
3-C
4) cycloalkenyl group ,-O (C
1-C
2) alkyl and-S (C
1-C
2) compound of alkane.
The compound of the preferred formula of another group (I) is R wherein
2 '-(L)-be the compound of the alkyl chain of 1 or 2 carbon atom.
The compound of the preferred formula of another group (I) is R wherein
20In R
80Group is selected from the compound of following groups: the relevant dibenzyl homologue of cycloalkyl, cycloalkenyl group, phenyl, naphthyl, norcamphyl, bicycloheptadiene base, tolyl, xylyl, indenyl, stilbenyl, terphenyl, diphenylacetylene, benzyl ring hexenyl, acenaphthenyl and anthryl, xenyl, dibenzyl and following formula (bb) representative
Wherein n is numerical value 1-8.Particularly preferably be wherein R
20Be selected from the compound of following groups:
R wherein
17Be independently selected from halogen ,-(C
1-C
10) alkyl ,-(C
1-C
10) alkoxyl group ,-S-(C
1-C
10) alkyl and-(C
1-C
10) haloalkyl, and w is numerical value 0-5.
The compound of the preferred formula of another group (I) is R wherein
2 'Be to contain an acid to connect basic length be the substituent compound that 2 or 3 acid connects base.Most preferably wherein acidic-group is selected from the compound of following groups:
-CO
2The H-5-tetrazyl ,-SO
3H
Wherein n is 1-8, R
89Be metal or-(C
1-C
10) alkyl, and R
99Be H or-(C
1-C
10) alkyl.Particularly preferably be wherein R
2 'Acidic-group be selected from the compound or its salt and prodrug (for example ester) derivative of following groups:
-CO
2H、-SO
3H、-P(O)(OH)
2
The compound of the preferred formula of another group (I) is that wherein R2 ' is that to contain its length be the substituent compound that 2 or 3 acid connects base, and wherein the acid of R2 ' connects base-(La)-the be selected from group of following formula representative:
Wherein Q is selected from group-(CH
2)-,-O-,-NH-and-S-, and R
84And R
85Be selected from independently of one another H ,-(C
1-C
10) alkyl, aryl ,-(C
1-C
10) alkylaryl ,-aryl (C
1-C
10) alkyl, carboxyl, carbalkoxy and halogen.Most preferably wherein the acid of R2 ' connects base-(La)-the be selected from compound of following special groups:
The compound of the preferred formula of another group (I) is that wherein R2 ' is the substituent compound that acid that to contain its length be 3-8 atom connects base, and wherein the acid of R2 ' connects base-(La)-the be selected from group of following formula representative:
Wherein r is 1-7, and s is 0 or 1, and Q is selected from group-(CH
2)-,-O-,-NH-and-S-, and R
84And R
85Be selected from independently of one another H ,-(C
1-C
10) alkyl, aryl ,-(C
1-C
10) alkylaryl ,-aryl (C
1-C
10) alkyl, carboxyl, carbalkoxy and halogen.
Most preferably wherein the acid of R2 ' connects base-(La)-the be selected from compound of following special groups:
R wherein
84And R
85Be selected from independently of one another H ,-(C
1-C
10) alkyl, aryl ,-(C
1-C
10) alkylaryl ,-aryl (C
1-C
10) alkyl, carboxyl, carbalkoxy and halogen.
The compound of the preferred formula of another group (III) is the R3 ' substituting group that is selected from H and do not interfere with each other wherein, and the substituting group that does not wherein interfere with each other is selected from following groups: H ,-(C
1-C
6) alkyl ,-(C
2-C
6) alkenyl ,-(C
2-C
6) alkynyl group ,-(C
7-C
12) arylalkyl ,-(C
7-C
12) alkylaryl ,-(C
3-C
8) cycloalkyl ,-(C
3-C
8) cycloalkenyl group, phenyl, tolyl, xylyl, xenyl ,-(C
1-C
6) alkoxyl group ,-(C
2-C
6) alkenyloxy ,-(C
2-C
6) chain oxy-acetylene ,-(C
1-C
12) alkoxyalkyl ,-(C
1-C
12) the alkoxyl group alkoxyl group ,-(C
1-C
12) alkyl-carbonyl ,-(C
1-C
12) alkyl-carbonyl-amino ,-(C
1-C
12) alkoxy amino ,-(C
1-C
12) the alkoxy amino carbonyl ,-(C
1-C
12) alkylamino ,-(C
1-C
6) alkylthio ,-(C
1-C
12) the alkylthio carbonyl ,-(C
1-C
6) alkyl sulphinyl ,-(C
1-C
6) alkyl sulphonyl ,-(C
1-C
6) halogenated alkoxy ,-(C
1-C
6) halogenated alkyl sulfonyl ,-(C
1-C
6) haloalkyl ,-(C
1-C
6) hydroxyalkyl ,-C (O) O (C
1-C
6Alkyl) ,-(CH
2)
nO (C
1-C
6Alkyl), benzyloxy, halogen, thiophenyl, quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces; Furyl, thienyl ,-(CH
2)
nCN ,-(CH
2)
nR
8R wherein
8Be H ,-CONH
2,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be independently-(C
1-C
4) alkyl or-phenyl (C
1-C
4) alkyl) ,-CHO, amino, amidino groups, formamyl, carboxyl, carbalkoxy ,-(CH
2)
nCO
2H, cyano group, cyano group guanidine radicals, guanidine radicals, hydrazide group, diazanyl, hydrazide group, hydroxyl, hydroxyl amino, nitro, phosphono ,-SO
3H, thioacetal, thiocarbonyl and-(C
1-C
6) alkyl-carbonyl, wherein n is 1-8.
R3 ' another the group preferred substituted comprise H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl, quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces ,-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl or-(CH
2)
nR
8, R wherein
8Be H ,-CONH
2,-NR
9R
10,-CN or phenyl (R wherein
9And R
10Be independently-(C
1-C
4) alkyl or-phenyl (C
1-C
4) alkyl), and n is 1-8.
Also have one group of preferred group comprise H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl, quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces ,-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl or-(CH
2)
nR
8, R wherein
8Be H ,-NR
9R
10,-CN or phenyl (R wherein
9And R
10Be independently-(C
1-C
4) alkyl or-phenyl (C
1-C
4) alkyl), and n is 1-8.
Preferred compound of the present invention is compound with following general formula (II), its pharmaceutically acceptable racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or salt:
Wherein: R
1Be-NHNH
2Or-NH
2R
2Be selected from-OH and-O (CH
2)
mR
5, wherein
R
5Be H ,-CO
2H ,-CO
2(C
1-C
4Alkyl),
Wherein R6 and R7 be independently of one another-OH or-O (C
1-C
4) alkyl ,-SO
3H ,-SO
3(C1-C4 alkyl), tetrazyl ,-CN ,-NH
2,-NHSO
2R
15,-CONHSO
2R
15, R wherein
15Be-(C
1-C
6) alkyl or-CF
3, phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that alkyl replaces, wherein m is 1-3; R
3Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl, quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces ,-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl or-(CH
2)
nR
8, R wherein
8Be H ,-CONH
2,-NR
9R
10,-CN or phenyl (R wherein
9And R
10Be independently-(C
1-C
4) alkyl or-phenyl (C
1-C
4) alkyl), and n is 1-8; R
4Be H ,-(C
5-C
14) alkyl ,-(C
3-C
14) cycloalkyl, pyridyl, phenyl or quilt-(C
1-C
6) alkyl, halogen ,-CF
3,-OCF
3,-(C
1-C
4) alkoxyl group ,-CN ,-(C
1-C
4) alkylthio ,-phenyl (C
1-C
4) alkyl ,-(C
1-C
4) phenyl of alkyl phenyl, phenyl, phenoxy group or naphthyl substituted; Z is cyclohexenyl or phenyl.
Substituting group on preferred formula I and the II compound comprises following groups:
(a) R
1Be-NH
2,-NHNH
2
(b) R
1Be-NH
2
(c) R
2Be O (CH
2)
mR
5, R wherein
5Be-H ,-CO
2H or
R wherein
6And R
7For-OH;
(d) R
2Be-OH;
(e) R
2Be-O (CH
2)
mR
5, R wherein
5Be-H ,-CO
2(C
1-C
4Alkyl), phenyl or quilt-CO
2H or-CO
2(C
1-C
4Alkyl) phenyl of Qu Daiing;
(f) R
2Be-O (CH
2)
mR
5, R wherein
5Be
And R6 and R7 are-O (C
1-C
4Alkyl), perhaps working as one of R6 and R7 is-O (C
1-C
4Alkyl) time, another is-OH;
(g) R
3Be-H ,-O (C
1-C
4Alkyl) or-(CH
2)
nR
8, n=2 wherein, and R
8Be H or phenyl;
(h) R
3Be H or O (C
1-C
4Alkyl);
(i) R
3Be-(CH
2)
nR
8, R wherein
8Be-NR
9R
10,-C=O (NH
2) or-CN, wherein R
9And R
10Be (C
1-C
4) alkyl;
(j) R
4It is phenyl;
(k) R
4Be 2 and 6 quilt-(C of phenyl ring
1-C
4) alkyl ,-(C
1-C
4) phenyl that replaces of alkoxyl group, halogen or phenyl;
(l) R
4Be 2 or 6 quilt-(C of phenyl ring
1-C
4) alkyl ,-(C
1-C
4) phenyl that replaces of alkoxyl group, halogen or phenyl;
(m) R
4Be 3 or 5 quilt-(C of phenyl ring
1-C
4) alkyl ,-(C
1-C
4) phenyl that replaces of alkoxyl group, halogen or phenyl;
(n) R
4Be-(C
6-C
14) alkyl or-(C
6-C
14) cycloalkyl;
(o) Z is a cyclohexenyl;
(p) R
5Be H ,-CO
2H ,-CO
2(C1-C4 alkyl),
-NHSO
2(C
1-C
6) alkyl ,-CONHSO
2(C
1-C
6) alkyl, tetrazyl, phenyl or quilt-CO
2H or-CO
2(C
1-C
4Alkyl) phenyl of Qu Daiing, wherein R
6And R
7Be independently of one another-OH or-O (C
1-C
4And m is 1-3 alkyl);
(q) R
5Be H ,-CO
2H ,-CO
2(C
1-C
4Alkyl),
Phenyl or quilt-CO
2H or-CO
2(C
1-C
4Alkyl) phenyl of Qu Daiing, wherein R
6And R
7Be independently of one another-OH or-O (C
1-C
4And m is 1-3 alkyl);
(f) Z is a cyclohexenyl;
(s) Z is a phenyl;
(t) R
5Be H ,-CO
2H ,-CO
2(C
1-C
4Alkyl) ,-P=O (R6R7), wherein R6 and R7 be independently of one another-OH or-O (C
1-C
4) alkyl ,-SO
3H ,-SO
3(C
1-C
4Alkyl), tetrazyl ,-CN ,-NH
2,-NHSO
2R
15,-CONHSO
2R
15, R wherein
15Be-(C
1-C
6) alkyl or-CF
3, phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that alkyl replaces, wherein m is 1-3; With
(u) R
3Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl, quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces ,-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkenyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group ,-(C
1-C
6) alkenyl or-(CH
2)
nR
8, R wherein
8Be H ,-CONH
2,-NR
9R
10,-CN or phenyl (R wherein
9And R
10Be independently H ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl or-phenyl (C
1-C
4) alkyl), and n is 1-8.
The further representative instance of useful formula I compound comprises among the present invention:
5-hydroxyl-7-(5-cyano group amyl group)-9-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
6-(2-carboxyl oxyethyl group)-8-methoxyl group-9-cyclopentyl-methyl-1,2,3,4-tetrahydro carbazole-4-methane amide;
5-(3-phenyl propoxy-)-7-oxyethyl group-9-butyl-1,2,3,4-tetrahydro carbazole-4-methane amide;
6-(2-phosphono oxyethyl group)-8-phenyl hexyl-9-(ring tetradecyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
5-ethoxycarbonyl methoxy-8-(5-formamyl penta-1-yl)-9-(3,5-dipropyl phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
6-(diethoxy phosphonium mesitoyl base) methoxyl group-9-(4-p-methoxy-phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
6-(3-(4-carboxyl phenyl) third-1-yl) oxygen base-8-heptyl-9-(3-phenylethyl) phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
6-(2-propoxycarbonyl) oxyethyl group-8-(3-(N, N-dimethylamino) third-1-yl)-9-methyl 1,2,3,4-tetrahydro carbazole-4-methane amide;
5-(two-tert.-butoxy phosphono) methoxyl group-7-nonyl-9-(3-rosickyite base phenyl) methyl 1,2,3,4-tetrahydro carbazole-4-methane amide;
5-(2-(3-methoxycarbonyl) phenyl) oxyethyl group-7-amyl group-9-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
6-hydroxyl-8-(4-(N, N-diethylamino) fourth-1-yl)-9-(3-fluorophenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
6-(2-phenyl ethoxy)-9-(2-phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
(S)-and 6-((3-carboxyl) third-1-yl) oxygen base-8-propoxy--9-(7-cyano group heptan-1-yl)-1,2,3,4-tetrahydro carbazole-4-methane amide;
5-(propoxycarbonyl) methoxyl group-9-cyclopentyl-methyl-1,2,3,4-tetrahydro carbazole-4-methane amide;
(S)-and 5-(2-oxyethyl group phosphono) oxyethyl group-(4-formamyl) fourth-1-base-9-(3-methylthio group phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
5-(3-(ethoxy carbonyl) third-1-yl) oxygen base 7-propoxy--9-(ring nonyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
5-(3-phosphono third-1-yl) oxygen base-8-heptyl-9-(4-chloro-phenyl-) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
6-methoxycarbonyl methoxyl group-7-(5-cyano group penta-1-yl)-9-tridecyl methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
(S)-and 6-propoxycarbonyl methoxyl group-9-((3-sec.-propyl-5-methoxyl group) phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
(S)-6-dimethoxy phosphono oxyethyl group-8-(6-(N, N-dimethylamino) oneself-1-base-9-(3, the 5-Dimethoxyphenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide;
5-hydroxyl-7-(5-cyano group amyl group)-9-methyl carbazole-4-methane amide;
6-(2-carboxyl oxyethyl group)-8-methoxyl group-9-cyclopentyl-methyl-carbazole-4-methane amide;
5-(3-phenyl third-1-yl) oxygen base-7-oxyethyl group-9-butyl carbazole-4-methane amide;
6-(2-phosphono oxyethyl group)-8-phenyl hexyl-9-(ring tetradecyl) methyl carbazole-4-methane amide;
5-ethoxycarbonyl methoxy-8-(5-formamyl penta-1-yl)-9-(3,5-dipropyl phenyl) methyl carbazole-4-methane amide;
6-(diethoxy phosphonium mesitoyl base) methoxyl group-9-(4-p-methoxy-phenyl) methyl carbazole-4-methane amide;
6-(3-(4-carboxyl phenyl) third-1-yl) oxygen base-8-heptyl-9-(3-phenylethyl) phenyl) methyl carbazole-4-methane amide;
6-(2-propoxycarbonyl) oxyethyl group-8-(3-(N, N-dimethylamino) third-1-yl)-9-methyl carbazole-4-methane amide;
5-((two-tert.-butoxy phosphono) methoxyl group-7-nonyl-9-(3-rosickyite base phenyl) methyl carbazole-4-methane amide;
(S)-5-(2-(3-methoxycarbonyl) phenyl) oxyethyl group-7-amyl group-9-methyl carbazole-4-methane amide;
(S)-6-hydroxyl-8-(4-N, N-diethylamino) fourth-1-yl)-9-(3-fluorophenyl) methyl carbazole-4-methane amide;
(S)-6-(2-phenyl ethoxy)-9-((2-phenyl) phenyl) methyl carbazole-4-methane amide;
6-((3-carbonyl) third-1-yl) oxygen base-8-propoxy--9-(7-cyano group heptan-1-yl)-carbazole-4-methane amide;
5-(propoxycarbonyl) methoxyl group-9-cyclopentyl-methyl carbazole-4-methane amide
5-(2-oxyethyl group phosphono) oxyethyl group-(4-formamyl) fourth-1-base-9-(3-methylthio group phenyl) methyl carbazole-4-methane amide;
5-((3-ethoxy carbonyl) third-1-yl) oxygen base-7-propoxy--9-(ring nonyl) methyl carbazole-4-methane amide;
(S)-5-(3-phosphono third-1-yl) oxygen base-8-heptyl-9-(4-chloro-phenyl-) methyl carbazole-4-methane amide;
(S)-6-methoxycarbonyl methoxyl group-7-(5-cyano group penta-1-yl)-9-tridecyl methyl carbazole-4-methane amide;
6-(propoxycarbonyl) methoxyl group-9-(3-sec.-propyl-5-methoxyl group) phenyl) methyl carbazole-4-methane amide;
6-dimethoxy phosphono oxyethyl group-8-(6-(N, N-dimethylamino) oneself-1-base-9 (3, the 5-Dimethoxyphenyl) methyl-carbazole-4-methane amide;
5-hydroxyl-7-(5-cyano group amyl group)-9-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
6-(2-carboxyl oxyethyl group-8-methoxyl group-9-cyclopentyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
5-(3-phenyl third-1-yl) oxygen base-7-oxyethyl group-9-butyl-1,2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
6-(2-phosphono oxyethyl group)-8-phenyl hexyl-9-(ring tetradecyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
5-ethoxycarbonyl methoxy-8-(5-formamyl penta-1-yl)-9-(3,5-dipropyl phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
(S)-and 6-(diethoxy phosphonium mesitoyl base) methoxyl group-9-(4-p-methoxy-phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
6-(3-(4-carboxyl phenyl) third-1-yl) oxygen base-8-heptyl-9-((3-phenylethyl) phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carbonyl hydrazides;
(S)-and 6-(2-propoxycarbonyl) oxyethyl group-8-(3-(N, N-dimethylamino) third-1-yl)-9-methyl 1,2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
5-(two-tert.-butoxy phosphono) methoxyl group-7-nonyl-9-(3-rosickyite base phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
(S)-and 5-(2-(3-methoxycarbonyl) phenyl) oxyethyl group-7-amyl group-9-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
6-hydroxyl-8-(4-(N, N-diethylamino) fourth-1-yl)-9-(3-fluorophenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
(S)-and 6-(2-phenyl ethoxy)-9-(2-phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
6-((3-carboxyl) third-1-yl) oxygen base-8-propoxy--9-(7-cyano group heptan-1-yl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
5-(propoxycarbonyl) methoxyl group-9-cyclopentyl-methyl-1,2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
5-(2-oxyethyl group phosphono) oxyethyl group-(4-formamyl) fourth-1-base-9 (3-methylthio group phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
5-(((ethoxy carbonyl) third-1-yl) oxygen base-7-propoxy--9-(ring nonyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
5-(3-phosphono third-1-yl) oxygen base-8-heptyl-9-(4-chloro-phenyl-) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
6-methoxycarbonyl methoxyl group-7-(5-cyano group penta-1-yl)-9-tridecyl-1,2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
6-propoxycarbonyl methoxyl group-9-(3-sec.-propyl-5-p-methoxy-phenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
6-dimethoxy phosphono oxyethyl group-8-(6-(N, N-dimethylamino) oneself-1-base-9-(3, the 5-Dimethoxyphenyl) methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
5-hydroxyl-7-(5-cyano group amyl group)-9-methyl carbazole-4-carboxylic hydrazides;
6-(2-carboxyl oxyethyl group)-8-methoxyl group-9-cyclopentyl-methyl-carbazole-4-carboxylic hydrazides;
5-(3-phenyl third-1-yl) oxygen base-7-oxyethyl group-9-butyl carbazole-4-carboxylic hydrazides;
6-(2-phosphono oxyethyl group-8-phenyl hexyl-9-(ring tetradecyl) methyl carbazole-4-carboxylic hydrazides;
5-ethoxycarbonyl methoxy-8-(5-formamyl penta-1-yl)-9-(3,5-dipropyl phenyl) methyl carbazole-4-carboxylic hydrazides;
6-(diethoxy phosphonium mesitoyl base) methoxyl group-9-(4-p-methoxy-phenyl) methyl carbazole-4-carboxylic hydrazides;
6-(3-(4-carboxyl phenyl) third-1-yl) oxygen base-8-heptyl-9-((3-phenylethyl) phenyl) methyl carbazole-4-carboxylic hydrazides;
6-(2-propoxycarbonyl) oxyethyl group-8-(3-(N, N-dimethylamino) third-1-yl)-9-methyl carbazole-4-carboxylic hydrazides;
5-(two-tert.-butoxy phosphono) methoxyl group-7-nonyl-9-(3-rosickyite base phenyl) methyl carbazole-4-carboxylic hydrazides;
5-(2-(3-methoxycarbonyl) phenyl) oxyethyl group-7-amyl group-9-methyl carbazole-4-carboxylic hydrazides;
6-hydroxyl-8-(4-(N, N-diethylamino) fourth-1-yl)-9-(3-fluorophenyl) methyl carbazole-4-carbazole;
6-(2-phenyl ethoxy)-9-(2-phenyl) methyl carbazole-4-carboxylic hydrazides;
6-((3-carboxyl) third-1-yl) oxygen base-8-propoxy--9-(7-cyano group heptan-1-yl)-carbazole-4-carboxylic hydrazides;
(S)-5-(propoxycarbonyl) methoxyl group-9-cyclopentyl-methyl carbazole-4-carboxylic hydrazides;
5-(2-oxyethyl group phosphono) oxyethyl group-(4-formamyl) fourth-1-base-9-(3-methylthio group phenyl) methyl carbazole 4-carboxylic hydrazides;
(S)-5-(3-(ethoxy carbonyl) third-1-yl) oxygen base-7-propoxy--9-(ring nonyl) methyl carbazole-4-carboxylic hydrazides;
5-(3-phosphono third-1-yl) oxygen base-8-heptyl 9-(4-chloro-phenyl-) methyl carbazole-4-carboxylic hydrazides;
6-methoxycarbonyl methoxyl group-7-(5-cyano group penta-1-yl)-9-tridecyl carbazole-4-carboxylic hydrazides;
6-propoxycarbonyl methoxyl group-9-((3-sec.-propyl-5-methoxyl group) phenyl) methyl carbazole-4-carboxylic hydrazides;
(S)-6-dimethoxy phosphono oxyethyl group-8-(6-(N, N-dimethylamino) oneself-1-base-9-(3, the 5-Dimethoxyphenyl) methyl carbazole-4-carboxylic hydrazides;
The 9-[(phenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-Phenoxyphenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-Phenoxyphenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(4-Phenoxyphenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9 - [(2 - fluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylsulfonyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylsulfonyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylsulfonyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - fluorenyl-methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazol-methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl - tetrazol-methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazol-methyl]-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylsulfonyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylsulfonyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylsulfonyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - fluorenyl-methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - methyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylsulfonyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylsulfonyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylsulfonyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} acetic acid radical;
9 - [(2 - thienyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - fluorenyl-methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - ethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylsulfonyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylsulfonyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylsulfonyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl] oxy acetic acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - fluorenyl-methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - propyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylsulfonyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylsulfonyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylsulfonyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - isopropyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9-[(4-trifluoromethylthio phenyl) methyl]-2-sec.-propyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(1-bromo-2-naphthyl phenyl) methyl]-2-sec.-propyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2-methyl isophthalic acid-naphthyl phenyl) methyl]-2-sec.-propyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(4-methyl isophthalic acid-naphthyl phenyl) methyl]-2-sec.-propyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(6-methyl-2-naphthyl phenyl) methyl]-2-sec.-propyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2-((benzenesulfonyl) methyl) phenyl) methyl]-2-sec.-propyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(1-fluorenyl methyl]-2-sec.-propyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(1-tetrazyl methyl]-2-sec.-propyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(5-methyl isophthalic acid-tetrazyl methyl]-2-sec.-propyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(5-benzyl-1-tetrazyl methyl]-2-sec.-propyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(phenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-Phenoxyphenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-Phenoxyphenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(4-Phenoxyphenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-fluorophenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-fluorophenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(4-fluorophenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-chloro-phenyl-) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-chloro-phenyl-) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(4-chloro-phenyl-) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-bromophenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-bromophenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(4-bromophenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-iodophenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-iodophenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(4-iodophenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-acetylamino phenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-acetylamino phenyl) methyl]-2-normal-butyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylsulfonyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylsulfonyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylsulfonyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(1 - fluorenyl-methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - n-butyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylsulfonyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylsulfonyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylsulfonyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acetic
9 - [(1 - fluorenyl-methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - n-pentyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylsulfonyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylsulfonyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylsulfonyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9-[(2, the 6-dichlorophenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(3, the 4-dichlorophenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(3, the 5-dichlorophenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2, the 3-3,5-dimethylphenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2, the 4-3,5-dimethylphenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2, the 5-3,5-dimethylphenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2, the 6-3,5-dimethylphenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(3, the 4-3,5-dimethylphenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(3, the 5-3,5-dimethylphenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2,4, the 6-trimethylphenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(3,5-two (trifluoromethyl) phenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2,4-two (trifluoromethyl) phenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2-fluoro-3-trifluoromethyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2-fluoro-4-trifluoromethyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2-fluoro-5-trifluoromethyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2-fluoro-6-trifluoromethyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(3-fluoro-5-trifluoromethyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(4-fluoro-2-trifluoromethyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(4-fluoro-3-trifluoromethyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[3-(2-fluorophenoxy) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[3-(4-fluorophenoxy) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2-fluoro-3-aminomethyl phenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(3-chlorine 2-fluorophenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2-chloro-6-fluorophenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(4-bromo-2-fluorophenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2-bromo-5-fluorophenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(3-chloro-4-aminomethyl phenyl) methyl]-2-trifluoromethyl 5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(3-chloro-4-p-methoxy-phenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(4-methoxyl group-3-aminomethyl phenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(4-trifluoromethylthio phenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(1-bromo-2-naphthyl phenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2-methyl 1-naphthyl phenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(4-methyl isophthalic acid-naphthyl phenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(6-methyl-2-naphthyl phenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2-((benzenesulfonyl) methyl) phenyl) methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(1-fluorenyl methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(1-tetrazyl methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(5-methyl isophthalic acid-tetrazyl methyl]-2-trifluoromethyl-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - trifluoromethyl-5 - carbamoyl-carbazol-4 - yl} phenoxy acetic acid;
9 - [(phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl]-2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl]-2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl]-2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methanesulfonyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methanesulfonyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl]-2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl]-2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl]-2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl]-2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl]-2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl]-2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl]-2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl]-2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-yl 3 - methylphenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - fluorenyl-methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - phenyl-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methanesulfonyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methanesulfonyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(1 - fluorenyl-methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - (4 - chlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - methanesulfonyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methanesulfonyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - cyano-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl carbazole 4 - yl} oxy acetic
Acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy
Acetic acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy
Acetic acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy
Acetic acid;
9 - [(1 - fluorenyl-methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - (2,4 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - methanesulfonyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methanesulfonyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - cyano-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl) oxy acetic acid;
9 - [(2 - naphthyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy
Acetic acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy
Acetic acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy
Acetic acid;
9 - [(1 - fluorenyl-methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - (2,6 - dichlorophenyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - (4 - methoxy-phenyl alkyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl) oxy acetic acid;
9 - [(4 - fluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - methanesulfonyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methanesulfonyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - cyano-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy
Acetic acid;
9 - [(1 - fluorenyl-methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - (4 - methoxyphenyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methanesulfonyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methanesulfonyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - yl] methyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - yl] methyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(1 - fluorenyl-methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - (hydroxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methanesulfonyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methanesulfonyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [{2,4 - dichlorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(1 - fluorenyl-methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - (methoxymethyl)-5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methanesulfonyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methanesulfonyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(1 - fluorenyl-methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - (2 - furyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenoxyphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - chlorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - iodo-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - acetylamino-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - carbamoyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methanesulfonyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - {(4 - methanesulfonyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxyphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - ethoxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethoxyphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - difluoromethoxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - pyridyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - furanyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - furanyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzoyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl) oxy acetic acid;
9 - [(2,4 - dichlorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dichlorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dichlorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dimethylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dimethylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dimethylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dimethylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,4 - dimethylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - dimethylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trimethylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3,5 - bis (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2,4 - bis (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-4 - (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - bromo - 2 - fluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-4 - methoxyphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methoxy-3 - methylphenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - trifluoromethylthio-phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(4 - methyl-1 - naphthyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acetic
Acid;
9 - [(1 - fluorenyl-methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(1 - tetrazolyl methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - methyl-1 - tetrazolyl methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(5 - benzyl-1 - tetrazolyl methyl] -2 - (2 - thienyl) -5 - carbamoyl-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxyphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - furyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - furyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxyphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl]-5 - carbamoyl-2 - oxide carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - furyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - furyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(1 - fluorenyl-methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(1 - fluorenyl-methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxyphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - furyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - furyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxyphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - chlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - methyl)-yl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - furyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - furyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - phenoxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - phenoxyphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluorophenyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - fluorophenyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - chlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetic acid
9 - [(3 - chlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - bromophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - bromophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - iodo-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - iodo-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - acetylamino-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - acetylamino-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - carbamoyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - carbamoyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - methylphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - methylphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - ethyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - ethylphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - methoxyphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclopropyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclobutyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclopentyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(cyclohexyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - methoxyphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - ethoxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - ethoxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - trifluoromethoxyphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - trifluoromethoxyphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - difluoromethoxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - difluoromethoxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - cyano-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - cyanophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - cyanophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - pyridyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - pyridyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - furyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - furyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - thienyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - thienyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzoyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzoyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - benzyloxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - benzyloxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - phenyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - phenyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(1 - naphthyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - naphthyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,5 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,6 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3,4 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3,5 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3,4 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3,5 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3,6 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4,5 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4,6 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3,4,5 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(pentafluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,3 - dichlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,4 - dichlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,5 - dichlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2,6 - dichlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(1 - fluorenyl-methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [3 - (4 - fluorophenoxy) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl) oxy acetic acid;
9 - [(3 - chloro-2 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - chloro-6 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - bromo-5 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - methyl-1 - naphthyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [3 - (2 - fluorophenoxy) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - fluoro-3 - methylphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(1 - bromo-2 - naphthyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(6 - methyl - 2 - naphthyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(1 - fluorenyl-methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acid;
9 - [(2 - thio phenoxy-phenyl) -5 - carbamoyl-carbazol-4 - yl] oxy acetic acid;
9 - [(3 - thio phenoxy-phenyl) -5 - carbamoyl-carbazol-4 - yl] oxy acetic acid;
9 - [(2 - methyl-9 - oxo-9H-thioxanthen-yl) -5 - carbamoyl-carbazol-4 - yl] oxy acetic acid;
9 - [(3 - phenoxyphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - chlorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - bromophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - acetylamino-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - acetylamino-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - carbamoyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ethyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - ethylphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methoxyphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(cyclopropyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(cyclopentyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(cyclohexyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methoxyphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - ethoxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - cyano-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - furyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - thienyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - thienyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzyl-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - naphthyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,5 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,6 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3,4 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3,5 - difluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,4 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(pentafluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3 - dichlorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4 - dichlorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,5 - dichlorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,6 - dichlorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - phenoxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - phenoxyphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - chlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - chlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - bromophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - bromophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - iodo-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - iodo-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - acetylamino-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - acetylamino-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - carbamoyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - carbamoyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methylphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methylphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ethyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - ethylphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methoxyphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(cyclopropyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(cyclobutyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(cyclopentyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(cyclohexyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methoxyphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ethoxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - ethoxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - cyano-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - cyanophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(4 - cyanophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - pyridyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - pyridyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - furyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - furyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - thienyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - thienyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzoyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzoyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(4 - benzyloxy-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - phenyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - phenyl-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(1 - naphthyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - naphthyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,3 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,4 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,5 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,6 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3,4 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3,5 - difluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,4 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,4,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(pentafluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,3 - dichlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,4 - dichlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,5 - dichlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,6 - dichlorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - phenoxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - phenoxyphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluorophenyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - fluorophenyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - chlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - chlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - bromophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - bromophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - iodo-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - iodo-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - acetylamino-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - acetylamino-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - carbamoyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - carbamoyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methanesulfonyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methanesulfonyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methylphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methylphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ethyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - ethylphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methoxyphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(cyclopropyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(cyclobutyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(cyclopentyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(cyclohexyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methoxyphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ethoxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - ethoxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - trifluoromethoxyphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - trifluoromethoxyphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - difluoromethoxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - difluoromethoxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - cyano-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - cyanophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - cyanophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - pyridyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - pyridyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - furyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - furyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - thienyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - thienyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzoyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzoyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzyloxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - benzyloxy-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - phenyl-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - phenyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(1 - naphthyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - naphthyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,5 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,6 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3,4 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3,5 - difluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,4 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,5 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,6 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4,5 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4,6 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3,4,5 - trifluoro-phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(pentafluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3 - dichlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4 - dichlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,5 - dichlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,6 - dichlorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [3 - (2 - fluorophenoxy) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [3 - (4 - O phenoxy) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-3 - methylphenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - fluoro-2 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - chloro-6 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - bromo-5 - fluorophenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(1 - bromo-2 - naphthyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methyl-1 - naphthyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(6 - methyl - 2 - naphthyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(1 - fluorenyl-methyl]-5 - carbamoyl-1 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [3 - (2 - fluorophenoxy) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [3 - (4 - fluorophenoxy) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-3 - methylphenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - chloro-2 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - chloro-6 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - bromo-5 - fluorophenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(1 - bromo-2 - naphthyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methyl-1 - naphthyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(6 - methyl - 2 - naphthyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(1 - fluorenyl-methyl]-5 - carbamoyl-1 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [3 - (2 - fluorophenoxy) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [3 - (4 - fluorophenoxy) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-3 - methylphenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - chloro-2 - fluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - chloro-6 - fluorophenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - bromo-5 - fluorophenyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(1 - bromo-2 - naphthyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methyl-1 - naphthyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(6 - methyl - 2 - naphthyl) methyl] -5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(1 - fluorenyl-methyl]-5 - amino-formyl-3 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - phenoxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - phenoxyphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - chlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - chlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - bromophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - bromophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - iodo-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - iodo-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - acetylamino-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - acetylamino-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - carbamoyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - carbamoyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methylphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methylphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ethyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - ethylphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methoxyphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(cyclopropyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(cyclobutyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(cyclopentyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(cyclohexyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methoxyphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ethoxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - ethoxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - cyano-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - cyanophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - cyanophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - pyridyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - pyridyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - furyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - furyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - thienyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - thienyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzoyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzoyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - phenyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - phenyl-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(1 - naphthyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - naphthyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,5 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,6 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3,4 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3,5 - difluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,4 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(pentafluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,3 - dichlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,4 - dichlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,5 - dichlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2,6 - dichlorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - phenoxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - phenoxyphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - chlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - chlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - bromophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - bromophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - iodo-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - iodo-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - acetylamino-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - acetylamino-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - carbamoyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - carbamoyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methanesulfonyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methylphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methylphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ethyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - ethylphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methoxyphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(cyclopropyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(cyclobutyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(cyclopentyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(cyclohexyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - methoxyphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ethoxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - ethoxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - trifluoromethoxyphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - difluoromethoxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - cyano-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - cyanophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(4 - cyanophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - pyridyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - pyridyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - furyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - furyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - thienyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - thienyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzoyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzoyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(4 - benzyloxy-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - phenyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - phenyl-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(1 - naphthyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - naphthyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,3 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,4 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,5 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,6 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3,4 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3,5 - difluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,4 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,3,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,4,6 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3,4,5 - trifluoro-phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(pentafluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,3 - dichlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,4 - dichlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,5 - dichlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2,6 - dichlorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [3 - (2 - fluorophenoxy) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [3 - (4 - fluorophenoxy) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-3 - methylphenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(3 - chloro-2 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - chloro-6 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - bromo-5 - fluorophenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(1 - bromo-2 - naphthyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - methyl-1 - naphthyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(6 - methyl - 2 - naphthyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(1 - fluorenyl-methyl]-5 - carbamoyl-2 - fluoro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-6 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - fluoro-5 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluoro-2 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(4 - fluoro-3 - (trifluoromethyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [3 - (2 - fluorophenoxy) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [3 - (4 - fluorophenoxy) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - fluoro-3 - methylphenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(3 - chloro-2 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - chloro-6 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - bromo-5 - fluorophenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(1 - bromo-2 - naphthyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 --1 - naphthyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(6 - methyl - 2 - naphthyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(2 - ((phenylsulfonyl) methyl) phenyl) methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - [(1 - fluorenyl-methyl]-5 - carbamoyl-2 - chloro-carbazol-4 - yl} oxy acetate;
9 - benzyl-4 - methoxy-benzenesulfonyl group - carbazole-5 - carboxamide;
9 - benzyl-4 - methoxy-Benzylsulfonylamino-carbazole-5 - carboxamide;
9 - Benzyl-4 - (2 - methoxy-methylphenylsulfonylamino) - carbazole-5 - carboxamide;
9 - Benzyl-4 - (naphthalen-2 - methoxy-ylsulfonamido) - carbazole-5 - carboxamide;
9 - benzyl-4 - methoxy-trifluoromethanesulfonylamino - carbazole-5 - carboxamide;
Among the formula I Z be tetrahydrobenzene compound according to reaction process I (a) and (c) preparation.
Reaction process I (a)
R wherein
1Be NH
2, R
3 (a)Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl, quilt-(C
1-C
6) alkyl, halogen or CF
3The phenyl that replaces ,-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkenyl, or-(CH
2)
nR
8, R wherein
8Be H ,-CONH
2, NR
9R
10,-CN or phenyl, wherein R
9And R
10Be hydrogen, CF independently of one another
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl or-phenyl (C
1-C
4) alkyl, n is 1-8.Work as R
1Be-NHNH
2The time, R
3 (a)Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl, quilt-(C
1-C
6) alkyl, halogen or CF
3The phenyl that replaces ,-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkenyl, or-(CH
2)
nR
8, R wherein
8Be H, NR
9R
10,-CN or phenyl, wherein R
9And R
10Be hydrogen, CF independently of one another
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl or-phenyl (C
1-C
4) alkyl, n is 1-8.R
2 (a)Be OCH
3Or OH.
Suitably the available reductive agent of the oil of mirbane (1) that replaces is handled it is reduced into aniline (2), as in the presence of Pd/C, uses hydrogen reduction, preferably at room temperature carries out.
Under about 0-20 ℃ temperature condition, use alkylating reagent, as the aldehyde of suitable replacement and sodium cyanoborohydride with compound (2) N-alkylation, generation (3).In addition, the benzyl halogen of available suitable replacement carries out the first step alkylation, and gained intermediate and 2-ethoxycarbonyl-6-bromine pimelinketone is handled, and preferably realizes further N-alkylation under about 40-80 ℃ temperature.Obtain (4), perhaps handle with hexamethyldisilane base ammonification potassium and bromo ketone ester.
With product (4) and ZnCl
2Refluxed about 1-2 days in benzene, cyclisation forms tetrahydro carbazole (5), and preferred temperature is 80 ℃ (reference 1).Under about 100 ℃ of temperature, compound (5) and hydrazine effect are converted into hydrazides (6), or in benzene, are converted into acid amides (7) (reference 2) with amino methyl aluminum chloride (methylchloroaluminum amide) reaction.(7) also can handle through active Raney nickel catalyst by (6) and obtain in addition.
Be understood that, work as R
3 (a)For-(CH
2)
nCOO (C
1-C
4Alkyl) time, employing this method also can realize the conversion to acid amides.
The available alkylation removal reagent in compound (6) and (7) carries out alkylation removal as boron tribromide or sulfo-sodium ethylate, preferably carries out under room temperature at 0 ℃, obtains R
2 (a)Be the compound (7) of-OH, this chemical combination materialization can further be converted into (9), and method is and alkali, as sodium hydride and the agent of alkylation formula, as Br (CH
2) mR
5Carry out alkylation again, wherein R
5Be carboxylicesters defined above, phosphodiester or nitrile, R
2Conversion to carboxylic acid can be by being used for finishing with alkali aqueous solution.Work as R
2When being nitrile, can be implemented to the conversion of tetrazolium, perhaps be implemented to the conversion of methane amide, work as R with the alkaline hydrogen peroxide reaction with the reaction of azide tributyl tin
2When being phosphodiester, can with alkylation removal reagent, be implemented to the conversion of acid as bromotrimethylsilane reaction, diester reacts with alkali aqueous solution can obtain its monoesters.
Work as R
2And R
3When all being methoxyl group, can be under 100 ℃, with the sulfo-sodium ethylate at dimethyl formamide reaction carrying out selectivity demethylation.Reference 1, Julia, M; Lenzi, J.1,2,3, the preparation of 4-tetrahydro carbazole-1 acid or-4 acid, Bull.Soc.Chim.France, 1962,2262-2263.Reference 2, Levin, J.I.; Turos, E.; Weinreb, the ester of S.M. aluminium mediation is converted into the other method of acid amides, Syn.Comm., 1982,12,989-993.
The other synthetic method of intermediate (5) is shown in following reaction process I (b).
Reaction process I (b)
Wherein PG is a protecting group, R
3 (a)Reaction process I defines as mentioned.
In the presence of 50 ℃ and sodium bicarbonate; in dimethyl formamide, aniline (2) was carried out the N-alkylation 8-24 hour with 2-ethoxycarbonyl-6-bromine pimelinketone; preferred protecting group comprises methyl, carbonic ether and silyl; as t-butyldimethylsilyl; adopt the condition of above-mentioned reaction process I (a), in benzene, use ZnCl
2With reaction product (4 ') cyclisation is (5 '), the N-alkylation of (5 ') to (5) by with sodium hydride and suitable haloalkane in dimethyl formamide under room temperature effect finished in 4-8 hour.
Reaction process II
R
3 (a)I defines as reaction process.Reaction process I is described as mentioned, and carbazole (5) is handled with alkali aqueous solution and is hydrolyzed to carboxylic acid (10), preferably carries out under room temperature-100 ℃.With intermediate product usefulness, for example oxalyl chloride and dimethyl formamide are converted into acyl chlorides then, again or (R) with (S)-and the lithium salts of 4-alkyl-2-Yang Dai oxazolidine react under-75 ℃ of temperature approximately and obtains (11a) and (11b), their available chromatography separation.
Diastereomer uses the benzyloxy lithium through simple process under about 0 ℃-room temperature; be translated into corresponding enantiomorph benzyl ester (12); (reference 3); ester (12) is preferably used amino methyl aluminum chloride (above reference 2) to handle and is converted into (7) then; perhaps adopt hydrogen as indicated above and palladium carbon to carry out hydrogenation in addition and make acid; with acyl azide,, use ammonia treatment then again as the diphenyl phosphoryl azide reaction.Adopt the method for above-mentioned reaction process I can obtain compound (9a) or (9b).Reference 3 Evans, D.A.; Ennis, M.D.; Mathre, the asymmetric alkylation reaction of D.J. chirality imide enolate, the practical approach that the selectivity of alpha-substituted carboxylic acid derivatives enantiomorph is synthetic, J.Am.Chem.Soc., 1982,104,1737-1738.
Z is that the compound of phenyl can be according to following reaction process III (a)-(f) 1 preparation among the formula I.
Reaction process III (a)
1,2,3,4-tetrahydro carbazole-4-methane amide or 4-formyl hydrazine (13) in the presence of Pd/C in solvent such as carbitol (Trivalin SF) the backflow dehydrogenation generate carbazole-4-methane amide.In addition, (13) act in appropriate solvent such as diox with DDQ and obtain carbazole (14).
According to substituent replacement mode, above-mentioned oxidation meeting causes the alkylation removal of nitrogen, for example works as R
3During with methyl substituted, oxidation causes the alkylation removal of nitrogen on the 8-position, and reaction process I is described as mentioned then, carries out alkylation again by handling with sodium hydride and suitable haloalkane, prepares required product (14).
Intermediate product can separate and purifying with routine techniques with final product, for example concentrated solvent, wash residue with water then, use the routine techniques purifying again, as chromatography or recrystallization.
It will be apparent to those skilled in the art that on raw material or the market availablely, perhaps can prepare easily by known technology as raw material by enough available from the market materials.Being used to prepare all other reaction reagents of The compounds of this invention is on the market available.
Reaction process III (b)
According to people such as Sakamoto; Chem.Pharm.Bull.35 (5); the described general condition of 1823-1828 (1987); in the presence of acid; use reductive agent; as tin protochloride benzoic acid derivative (16) is reduced to corresponding aniline (25), preferably chlorine, bromine or iodine of X wherein, protecting group preferably-CH
3
In addition, at alkali, under sodium carbonates' presence, in non-interference with solvent such as water, ethanol and/or tetrahydrofuran (THF), can obtain raw material (16) with the sodium disulfide reduction.
In addition, in the presence of the sulfurized platinum catalyst that carbon is supported, in non-interference with solvent, carry out hydro-reduction in the ethyl acetate and can generate initial substance (16) with the atmospheric hydrogen of 1-60.
Be reflected at 0-100 ℃, preferably under ambient temperature, carry out,, be reflected at and carry out substantially in about 1-48 hour fully according to the difference of approach.
Aniline (25) and diketone (15) condensation under dehydrogenation condition for example, are adopted people's such as Iida method (reference 5), use or do not use non-interference with solvent, as toluene, benzene or methylene dichloride, carry out under 10-150 ℃ of temperature at dehydrogenation condition.Removing the water that generates in the reaction process can adopt distillation, remove or add siccative by Dean-Stark device azeotropic, as molecular sieve, sal epsom, lime carbonate, sodium sulfate or the like.
React the acid that can use or not use catalytic amount, as tosic acid or methylsulfonic acid, other suitable catalyzer example comprises spirit of salt, Phenylsulfonic acid, calcium chloride and acetate.
The example of other appropriate solvent comprises tetrahydrofuran (THF), ethyl acetate, methyl alcohol, ethanol, sym.-tetrachloroethane, chlorobenzene, bromobenzene, dimethylbenzene and tetracol phenixin.
This condensation course preferably under 100-150 ℃ of temperature net phase carry out, the water that is generated is removed by inert gas distillation, as nitrogen or argon gas.
Be reflected in about 30mins-24hrs and finish substantially.
Intermediate product (26) is under 25-200 ℃ of temperature, and in non-interference with solvent, in acetonitrile, triethylamine or toluene, cyclisation easily forms (19) under the condition that following material exists: palladium catalyst, and as Pd (OAc)
2Or Pd (PPh
3)
4Deng; Phosphine, preferred trialkyl phosphine or triaryl phosphine are as triphenylphosphine, tri-o-tolyl phosphine or tricyclohexyl phosphine etc.; Alkali is as sodium bicarbonate, triethylamine or diisopropylethylamine etc.
The example of other appropriate solvent comprises tetrahydrofuran (THF), benzene, methyl-sulphoxide or dimethyl formamide.
The example of other suitable palladium catalyst comprises Pd (PPh
3) Cl
2, Pd (OCOCF
3)
2, [(CH
3C
6H
4)
3P]
2PdCl
2, [(CH
3CH
2)
3P]
2PdCl
2, [(C
6H
11)
3P]
2PdCl
2[(C
6H
5)
3P]
2PdBr
2
The example of other suitable phosphine comprises tri isopropyl phosphine, triethyl phosphine, three cyclopentyl phosphines, 1, two (diphenylphosphino) ethane, 1 of 2-, two (diphenylphosphino) propane and 1 of 3-, two (diphenylphosphino) butane of 4-.
The example of other suitable alkali comprises tripropyl amine, 2,2,6,6-tetramethyl piperidine, 1,5-diazabicylo [2.2.2] octane (DABCO), 1,8-diazabicylo [5.4.0] 11 carbon-7-alkene (DBU), 1,5-diazabicylo [4.3.0] ninth of the ten Heavenly Stems-7-alkene (DBN), yellow soda ash, salt of wormwood and saleratus.
The preferred implementation condition of this cyclisation step is: with acid chloride (II) is catalyzer, at triphenyl phosphine, tri-o-tolyl phosphine, 1, one of two (diphenylphosphino) propane of 3-or tricyclohexyl phosphine exist down, are solvent with the acetonitrile, with the triethylamine is alkali, and temperature is 50-150 ℃.Be reflected in about 1h-14 days and finish substantially.
Preferred in addition cyclisation step is to use palladium to become ring catalyzer (palladacycle catalist), as trans-two (μ-acetoxyls)-two [neighbour-(two-neighbour-tolyl phosphino-) benzyl] two palladiums (II), solvent such as N,N-DIMETHYLACETAMIDE (DMAC), 120-140 ℃, under the condition that alkali such as sodium acetate exist, intermediate product (26) is reacted.
In the presence of alkali, intermediate product (19) can be used alkylating reagent XCH
2R
4Carry out alkylation and generate (20), wherein X is a halogen.Suitable alkali comprises salt of wormwood, yellow soda ash, Quilonum Retard, cesium carbonate, sodium bicarbonate, saleratus, potassium hydroxide, sodium hydroxide, sodium hydride, potassium hydride KH, lithium hydride and Triton B (hydroxide N-benzyltrimethylammon.um).
Reaction can be carried out being with or without in the presence of the crown ether, and salt of wormwood and Triton B are preferred, and the amount of alkylating reagent is not strict, but preferably uses the haloalkane excessive with respect to initial substance, so that reaction is finished best.
Can add or not add the iodide of catalytic amount in the reaction mixture, as sodium iodide, lithium iodide.Reaction is preferably carried out in organic solvent, and as acetone, dimethyl formamide, methyl-sulphoxide or acetonitrile, other appropriate solvent comprises tetrahydrofuran (THF), methyl ethyl ketone and t-butyl methyl ether.
Be reflected under the pact-10-100 ℃ of temperature and carry out, preferably at room temperature carry out.Rely on different conditions, be reflected in about 1-48 hour and finish substantially.Randomly, can use phase transfer reagent, as bromination tetrabutylammonium or TBAC tetrabutylammonium chloride.
Intermediate product (20) can be with 2 in non-interference with solvent, 3-two chloro-5, and 6-dicyano-1, the oxydehydrogenation of 4-benzoquinones generates (21).
Appropriate solvent comprises methylene dichloride, chloroform, tetracol phenixin, ether, methyl ethyl ketone, t-butyl methyl ether, preferred toluene, benzene, diox and tetrahydrofuran (THF).Be reflected at about 0-120 ℃, preferably under 50-120 ℃ of temperature, carry out.Rely on different conditions, be reflected at about 1-48 hour and finish substantially.
Intermediate product (21) can carry out amination with ammonia in non-interference with solvent, generate (22).Ammonia can be ammonia or ammonium salts, as ammonium hydroxide, ammonium acetate, trifluoroacetic acid ammonium, ammonium chloride or the like.Appropriate solvent comprises ethanol, methyl alcohol, propyl alcohol, butanols, tetrahydrofuran (THF), diox and water.This method is preferably used ammonium hydroxide solution,stronger and tetrahydrofuran (THF) or methanol mixture, is reflected at about 20-100 ℃, preferably carries out under 50-60 ℃ of temperature.Rely on different conditions, be reflected in about 1-48 hour and finish substantially.
In the presence of alkali in non-interference with solvent, with formula XCH
2R
9The alkylating agent effect is carried out alkylation with (22) and is generated (23), and wherein X is a halogen, R
70Be-CO
2R
71,-SO
3R
71,-P (O) (OR
71)
2Or-P (O) (OR
71) H, wherein R
71Be sour protecting group or prodrug functional group, preferred methyl bromoacetate of alkylating agent and bromo-acetic acid tert-butyl.
Suitable alkali comprises salt of wormwood, yellow soda ash, cesium carbonate, Quilonum Retard, sodium bicarbonate, saleratus, potassium hydroxide, sodium hydroxide, sodium hydride, potassium hydride KH, lithium hydride and Triton B (hydroxide benzyltrimethylammon.um), reaction can be carried out being with or without in the presence of the crown ether, and cesium carbonate and Triton B are preferred.
The amount of alkylating agent is not strict, but preferably uses the haloalkane excessive with respect to initial substance, to finish reaction.Reaction is preferably carried out in organic solvent, and as acetone, dimethyl formamide, methyl-sulphoxide or acetonitrile, other appropriate solvent comprises tetrahydrofuran (THF), methyl ethyl ketone and t-butyl methyl ether.
Be reflected under the pact-10-100 ℃ of temperature and carry out, preferably at room temperature carry out.Rely on different conditions, be reflected at about 1-48 hour and finish substantially.Randomly, can use phase transfer reagent, as bromination tetrabutylammonium or TBAC tetrabutylammonium chloride.
Intermediate product (23) can randomly generate needed product (24) and randomly form salt with alkali or acid hydrolysis.
(23) be hydrolyzed, use alkali such as sodium hydroxide, potassium hydroxide, lithium hydroxide, wet chemical, aqueous sodium carbonate, lithium carbonate aqueous solution, potassium bicarbonate aqueous solution, sodium bicarbonate aqueous solution, the lithium bicarbonate aqueous solution, preferred sodium hydroxide, and lower alcohol solvent, as methyl alcohol, ethanol, Virahol or the like, other appropriate solvent comprises acetone, tetrahydrofuran (THF) He diox.
In addition, sour protecting group can have or interference with solvent exists nothing but condition under, slough with organic or inorganic acid, as trifluoroacetic acid and hydrochloric acid.Appropriate solvent comprises methylene dichloride, tetrahydrofuran (THF), diox and acetone.The tert-butyl ester is preferably sloughed with pure trifluoroacetic acid.
Be reflected under the pact-10-100 ℃ of temperature and carry out, preferably at room temperature carry out.Rely on different conditions, be reflected in about 1-48 hour and finish substantially.
Preparation raw material (16) is to use alkyl chloride=XPG with compound (15) esterification, and wherein X is a halogen, and PG is sour protecting group, and reaction conditions is to have alkali to exist, preferred salt of wormwood and yellow soda ash; Adopt non-interference with solvent, preferred dimethyl formamide or methyl-sulphoxide.Preferred alkyl chloride is a methyl iodide.Be reflected under about 0-100 ℃ temperature and carry out, preferably at room temperature carry out.Rely on different conditions, be reflected in about 1-48 hour and finish substantially.
In addition, raw material (16) can exist down as dicyclohexylcarbodiimide (DDC) or carbonyl dimidazoles at dehydration catalyst, is prepared with pure HOPG condensation, and wherein PG is sour protecting group.
In addition, U.S. Patent No. 4,885,338 and Jpn.Kokai Tokkyo Koho 05286912, Nov.1993 Hesei has pointed out to prepare the method for 2-fluoro-5-anisole sulfonamide derivatives.
Reaction process III (c)
R such as reaction process III (b) definition; R
3 (a)Such as above-mentioned reaction process I (a) definition; X is a halogen.
Benzoic acid derivative (16) (X=Cl, Br or I) and boric acid derivatives (27) (on the market available or can with the preparation easily according to known technique of available initial substance on the market), according to described general methods of people (reference 8b) such as people such as Miyaura (reference 8a) or Trecourt, specifically be at palladium catalyst, as Pd (Ph
3P)
4And alkali, under the existence as sodium bicarbonate, in inert solvent (as THF, toluene or ethanol), carry out condensation, obtain compound (28).
According to the described general method of people such as Cadogan (reference 6),,, compound (28) is converted into carbazole product (29) as triethyl-phosphite or triphenylphosphine effect with tricresyl phosphite alkyl or triaryl ester or phosphine.
At alkali, under the existence as sodium hydride or salt of wormwood, in non-interference with solvent, in toluene, dimethyl formamide or methyl-sulphoxide, with the alkylogen or the aryl halide XCH of compound (29) with suitably replacement
2R
4Carry out the N-alkylation, obtain carbazole (30).
Compound (30) is converted into corresponding amide, and method is and boron tribromide or the effect of sulfo-sodium ethylate; Then under 0-110 ℃ of temperature, at inert solvent, as in water or the alcohol with ammonia or ammonium salt, as the ammonium acetate effect, perhaps at inert solvent, as in the toluene with the effect of amino methyl aluminum chloride.
As mentioned above, work as R
3 (a)When replacing with chlorine on the 8-position, the alkylation removal effect of (30) and boron tribromide causes the benzylation of going on the nitrogen-atoms.Its alkylation can be easily be undertaken by two steps, at first is to carry out the O-alkylation with the alkyl halogen acetates effect, as use sodium hydride in tetrahydrofuran (THF) with the methyl bromoacetate effect.Be the N-alkylation then, for example use alkali, in the dimethoxy methane amide, react as sodium hydride and suitable alkylogen and the aryl halide that replaces.According to above reaction process III (b) is described, compound (22) can be converted into product carbazole (24).
Being converted into needed prodrug can realize by the technology that the technician knows, and for example makes ester class prodrug with uncle or secondary (alkyl) halogenide effect.
Reaction process III (d)
In addition, the nitro of compound (28) is pressed described reduction and obtained corresponding aniline (32): use reductive agent, as use hydrogen in the presence of palladium carbon, in non-interference with solvent, in ethanol, 1-60 normal atmosphere carries out under the 0-60 ℃ of temperature.According to the described general method of people such as Trecourt (reference 8b), compound (32) is converted into carbazole (29), described aniline and sulfuric acid and Sodium Nitrite effect, generate the trinitride intermediate with reaction of sodium azide then, this intermediate is in inert solvent, turn to carbazole (29) as heating ring in the toluene, described according to preamble reaction process III (b) and reaction process III (c), compound (29) is converted into carbazole product (24).Reference: 8) a. N.Miyaura, wait the people, Synth.Comm.11,513 (1981) b. F.Trecourt wait the people, Tertahedron, 51,11,743 6) 6) J.Cadogan, wait the people, J.Chem.Soc., 4831 (1965)
Flow process III (e)
At aprotonic solvent, in the preferred tetrahydrofuran (THF), use reductive agent (as three aluminum hydride) to finish the reduction reaction of (40); Carry out in the preferred inert atmosphere (as nitrogen) at room temperature of this reaction.
At acid scavenger, exist down as triethylamine, can finish sulfonylation with suitable acylating agent.
Flow process III (f)
In two-step type one pot process, at first will use activator as the intermediate (50) that makes as described in the flow process I (a), activate as carbonyl dimidazoles; This reaction is preferably at non-proton transmission polarity or non-polar solvent, as carrying out in the tetrahydrofuran (THF).Then, at alkali, preferred diazabicylo undecylene exists down, by with H
2NSOR
15The acylation reaction of activated intermediate is finished in reaction.
Flow process III (g)
PG is sour protecting group; R
22Be (C
1-C
6) alkoxyl group (C
1-C
6) alkyl or (C
1-C
6) alkoxyl group (C
1-C
6) alkenyl.
Under the nitrogen atmosphere at room temperature, in non-proton transfering polarity solvent (preferred dry DMF), in the presence of alkali (as NaH), make starting material (20) O-alkylation with alkylogen or alkenyl halogen.In the anhydrous solvent in the presence of the benzene sulfinic acid methyl esters (as 1,4-diox or DMF), cyclonene functional group aromatization can be turned to phenol functional group to form the ketone sulfoxide derivant by handle tetrahydro carbazole intermediate (60) with alkali (as NaH); After 1 to 2 hour, ketone sulfoxide derivant (60) is converted into phenol derivatives (61) in about 100 ℃ of heating.In non-proton transfering polarity solvent (as tetrahydrofuran (THF)), by ester (61) being converted into acid amides (62) with ammonia treatment soln (61); At room temperature, in dry DMF, use Cs as alkali
2CO
3Or K
2CO
3By with (62) and for example methyl bromoacetate reaction, can finish the O-alkylation formation (63) of phenol; H under 50 ℃
2O/CH
3In the OH/THF solution, use as the LiOH of alkali or NaOH by ester (63) alkaline hydrolysis can be obtained required product (64) in 1 to 2 hour.
Work as R
22Be (C
1-C
6) alkoxyl group (C
1-C
6) during alkenyl, in THF by using PtO
2Make catalyzer and in hydrogen, handle the hydrogenation that (63) can finish two keys; Then, the H under 50 ℃
2O/CH
3In the OH/THF solution, use as the LiOH of alkali or NaOH by ester (63) alkaline hydrolysis can be obtained required product in 1 to 2 hour as described in above flow process III (g).
Abbreviation below in embodiment and preparation example, using: Hcl=hydrochloric acid EtOAc=ethyl acetate DMF=dimethyl formamide THF=tetrahydrofuran (THF) Et
2O=ether H
2O=water NaOH=sodium hydroxide EtOH=ethanol Na
2SO
4=sodium sulfate NaHCO
3=sodium bicarbonate celite=diatomite CH
2Cl
2=methylene dichloride H
2SO
4=sulfuric acid MeOH=methyl alcohol Rh/Al
2O
3=rhodium and aluminum oxide DDQ=2,3-two chloro-5,6-dicyano-1,4-benzoquinones TLC=thin-layer chromatography NaH=sodium hydride NH
4OH=ammonium hydroxide LiOH=lithium hydroxide NH
3=ammonia Cs
2CO
3=cesium carbonate NH
4The OAc ammonium acetate
The preparation example of following intermediate and the embodiment of final product will further specify the preparation of The compounds of this invention, and still, used embodiment only is illustrative, in any case and do not limit the scope of the present invention.Embodiment 19-benzyl-5,7-dimethoxy-1,2,3, the 4-tetrahydro carbazole-preparation A of 4-carboxylic hydrazides, N-benzyl-3, the preparation of 5-dimethoxyaniline
With 25g. (0.163mol) 3, the solution that 5-dimethoxyaniline and 18.3ml (0.18mol) phenyl aldehyde forms in 300ml methyl alcohol cools off in frozen water and uses 10.3g. (0.18mol) sodium cyanoborohydride to handle in batches.With this solution stirring and cooling 3 hours, with 1 to 2g sodium borohydride processing 30 minutes, dilute with water and use ethyl acetate extraction.Again organic phase is used the salt water washing, with dried over sodium sulfate and vacuum-evaporation.With resistates chromatogram on silica gel, and be wash-out under the condition of hexane/15-70% ether in gradient, obtain 28.0g oily N-benzyl-3,5-dimethoxyaniline, yield are 71%.C
15H
17NO
2Ultimate analysis:
Calculated value: C74.05; H7.04; N5.76
Measured value: C74.30; H7.12; N5.70B, 9-benzyl-5,7-dimethoxy-1,2,3, the preparation of 4-tetrahydro carbazole-4-carboxylic hydrazides
With 9.72g.A stepwise compound and 4.98g2-ethoxycarbonyl-6-bromine hexanaphthene ketone (J.Sheehan and C.E.Mumaw, J.Am.Chem.Soc., 72,2127-2129, (1950)) solution that forms in 125ml benzene refluxed cooling 72 hours, filter, and under vacuum condition, evaporate.Resistates (12g) and 10g zinc chloride were refluxed 6 hours in 250ml benzene, and cooling is also evaporated under vacuum condition.Again resistates is dissolved in ethyl acetate,, washes with water, use dried over sodium sulfate, and under vacuum condition, evaporate with 1N salt acid elution.With resistates chromatogram on silica gel, and be wash-out under the condition of toluene/0-5% ethyl acetate in gradient, obtain 1.88g. compound (5) (R
2=5-MeO, R
3=7-MeO, R
4=phenyl); Then, it is dissolved in 100ml contains the 100ml ethanol of 10ml hydrazine hydrate and refluxed 5 days, cooling is with the solution decant, with the ethyl acetate dilution, use the salt water washing, use dried over sodium sulfate, and under vacuum condition, evaporate, obtain the 1.1g title compound, yield is 60%, mp:189-190 ℃/CH
2Cl
2-EtOHC
22H
25N
3O
3Ultimate analysis:
Calculated value: C69.64; H6.64; N11.07
Measured value: C69.59; H6.74; N10.84 embodiment 29-benzyl-5,7-dimethoxy-1,2,3, the preparation of 4-tetrahydro carbazole-4-methane amide
With 980mg embodiment 1 compound, 2g Raney nickel catalyst, 1 to 2ml hydrazine hydrate and 125ml alcohol reflux 1 hour, with the solution decant,, use the salt water washing with the ethyl acetate dilution, use dried over sodium sulfate, and under vacuum condition, evaporate; With resistates chromatogram on silica gel, and be wash-out under the condition of methylene dichloride/1-3% methyl alcohol in gradient, obtain the 820mg title compound, yield is 84%, mp:190-192 ℃/EtOH.C
22H
24N
2O
3Ultimate analysis:
Calculated value: C72.51; H6.64; N7.69
Measured value: C71.88; H6.89; N7.81 embodiment 3[9-benzyl-4-formamyl-7-methoxyl group-1,2,3,4-tetrahydro carbazole-5-yl] preparation A, the 9-benzyl-5-hydroxyl-7-methoxyl group-1,2,3 of ethoxyacetic acid sodium salt, the preparation of 4-tetrahydro carbazole-4-methane amide
The solution that 1.75g (4.8mmol) embodiment 6 compounds are formed in the 50ml dimethyl formamide mixes with the solution that sulfo-sodium ethylate (13.5mmol) forms in the 75ml dimethyl formamide, heats 21 hours down at 100 ℃ then.With the mixture cooling, dilute with water is used hcl acidifying, and uses ethyl acetate extraction.Again organic phase is used the salt water washing, used dried over sodium sulfate, and under vacuum condition, evaporate; With resistates chromatogram on silica gel, and be wash-out under the condition of methylene dichloride/0-4% methyl alcohol in gradient, obtain 825mg subhead compound, yield is 50%, mp:225-7 ℃/ethanol.C
21H
22N
2O
3Ultimate analysis:
Calculated value: C71.98; H6.33; N7.99
Measured value: C71.71; H6.37; The preparation of N7.72B, [9-benzyl-4-formamyl-7-methoxyl group-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid ethyl ester
(60% in mineral oil with the 100mg sodium hydride, 2.5mmol) handle the solution 10 minutes that the product of 700mg (2.0mmol) A step forms in 70ml dimethyl formamide and 15ml tetrahydrofuran (THF), then handled 3 hours with 0.3ml (2.7mmol) bromoethyl acetate.Mixture is diluted with ethyl acetate, wash with water, use the salt water washing, use dried over sodium sulfate, and under vacuum condition, evaporate; With resistates chromatogram on silica gel, and be wash-out under the condition of methylene dichloride/1-2% methyl alcohol in gradient, obtain 670mg subhead compound, yield is 77%, mp:167-169 ℃/ether.C
25H
28N
2O
5Ultimate analysis:
Calculated value: C68.79; H6.47; N6.42
Measured value: C69.57; H6.39; The preparation of N5.77C, [9-benzyl-4-formamyl-7-methoxyl group-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid
The suspension that the product of 650mgB step is formed in 20ml tetrahydrofuran (THF) and 70ml ethanol is with 5ml 2N sodium-hydroxide treatment, and with the solution stirring that generates 15.5 hours.Then, solution is diluted with ethyl acetate and water, and use hcl acidifying.Organic phase is used the salt water washing again, used dried over sodium sulfate, concentrate under vacuum condition, and filter, obtain the 540mg title compound, yield is 87%, mp:251-254 ℃.C
23H
24N
2O
5Ultimate analysis:
Calculated value: C67.63; H5.92; N6.86
Measured value: C67.73; H5.74; The preparation of N6.82D, [9-benzyl-4-formamyl-7-methoxyl group-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid sodium salt
The suspension that the product of 120mgC step is formed in 20ml ethanol is with 0.15ml 2N sodium-hydroxide treatment, and heating is until dissolving.The solution that generates is concentrated under vacuum condition, dilute with ethyl acetate; Then, under vacuum condition, concentrate and standing over night again.Precipitation is leached and air-dry, obtain 80mg amorphous solid shape title compound 80mg, yield is 63%.C
23H
23NaN
2O
50.4H
2The O ultimate analysis:
Calculated value: C63.18; H5.39; N6.40
Measured value: C63.31; H5.48; N6.25 embodiment 4[9-benzyl-4-formamyl-7-methoxyl group carbazole-5-yl] preparation of ethoxyacetic acid
The mixture heating up of product, 2g 5%Pd/C and the 20ml Trivalin SF of the D step of 430mg embodiment 3 until backflow, and was refluxed 21 hours, and then, cooling is also filtered.With the filtrate water dilution, use hcl acidifying, and thoroughly extract with ethyl acetate.Again organic phase is used the salt water washing, used dried over sodium sulfate, and under vacuum condition, evaporate.Resistates is developed with methylene dichloride, and filtering solid tetrahydro carbazole.At last, evaporated filtrate under vacuum condition obtains the 125mg title compound, and yield is 31%.C
23H
20N
2O
50.4H
2The O ultimate analysis:
Calculated value: C67.11; H5.09; N6.81
Measured value: C67.25; H5.19; N6.75 embodiment 5[9-benzyl-4-formamyl-7-methoxyl group carbazole-5-yl] preparation A, the 9-benzyl-4-formamyl-5 of ethoxyacetic acid methyl esters, the preparation of 7-dimethoxy carbazole
The mixture of product, 2g 5%Pd/C and the 100ml Trivalin SF of 2.0g embodiment 2 was refluxed 17 hours, filtered while hot, and thoroughly wash the gained solid with ethyl acetate.After the filtrate water washing after merging, use the salt water washing again, use dried over sodium sulfate, and under vacuum condition, evaporate, obtain 1.4g subhead product, yield is 70%, mp:240-243 ℃.C
22H
20N
2O
3Ultimate analysis:
Calculated value: C73.32; H5.59; N7.77
Measured value: C74.26; H5.73; The preparation of N8.04B, 9-benzyl-4-formamyl-5-hydroxyl-7-methoxyl group carbazole
Under 100 ℃, with the 100ml dimethyl formamide solution heating of the product of 1.2g (3.3mmol) A step and 10mmol sulfur alcohol sodium 42 hours, cooling, dilute with water, and pH is transferred to 5-6 with hydrochloric acid.Use the ethyl acetate extraction mixture, organic phase is washed with water, use the salt water washing again, use dried over sodium sulfate, and under vacuum condition, evaporate.With resistates chromatogram on silica gel, obtain the 550mg product with eluent ethyl acetate, yield is 48%, mp:234-236 ℃ of decomposition.C
21H
18N
2O
3Ultimate analysis:
Calculated value: C72.82; H5.24; N8.09
Measured value: C72.54; H5.19; The preparation of N8.04C, [9-benzyl-4-formamyl-7-methoxyl group carbazole-5-yl] ethoxyacetic acid methyl esters
(60% in mineral oil with the 60mg sodium hydride with solution that the product of 430mg (1.2mmol) B step forms in 40ml dimethyl formamide and a few ml tetrahydrofuran (THF), 1.5mmol) handled 15 minutes, then handled 16 hours with 0.13ml (1.4mmol) monobromo-acetic acid methyl esters; With the ethyl acetate dilution, wash with water, use the salt water washing, use dried over sodium sulfate, and under vacuum condition, evaporate; With resistates chromatogram on silica gel, and be wash-out under the condition of methylene dichloride/1-3% methyl alcohol in gradient, obtain the 320mg title compound, yield is 62%, mp:170-172 ℃.C
24H
22N
2O
5Ultimate analysis:
Calculated value: C68.89; H5.30; N6.69
Measured value: C68.64; H5.41; The preparation of N6.57D, [9-benzyl-4-formamyl-7-methoxyl group carbazole-5-yl] ethoxyacetic acid sodium salt
The sodium hydroxide of 0.075ml 2.0N is added in the suspension that the product of 60mg (0.15mmol) C step forms in 30ml ethanol; Heat this mixture until forming solution, cooling then concentrates under vacuum condition, with the ethyl acetate dilution, under vacuum condition, concentrate again, and cooling, and filter, obtaining the product of 50mg amorphous solid shape, yield is 80%.MS (FAB+) 427.2:MS (ion injection)+Q1 405.5 ,-Q1 403.5 embodiment 69-benzyls-7-methoxyl group-5-cyano group methoxyl group-1,2,3, the preparation of 4-tetrahydro carbazole-4-methane amide
(60% in mineral oil with the 210mg sodium hydride with solution that the products of A step of 1.47 gram (4.19mmol) embodiment 3 form in 146ml dimethyl formamide and 31ml tetrahydrofuran (THF), 5.24mmol) handled 10 minutes, then use 0.39ml (0.66mmol) bromo acetonitrile treatment 3.5 hours; Mixture is diluted with ethyl acetate, wash with water, use the salt water washing, use dried over sodium sulfate, and under vacuum condition, evaporate; With resistates chromatogram on silica gel, and carry out gradient elution with the methylene dichloride that contains 0-4% methyl alcohol, obtain the 1.34g title compound, yield is 82%.C
23H
23N
3O
3Ultimate analysis:
Calculated value: C70.93; H5.95; N10.79
Measured value: C70.67; H6.06; N10.83 embodiment 79-benzyl-7-methoxyl group-5-(1H-tetrazolium-5-ylmethyl) Oxy-1,2,3, the preparation of 4-tetrahydro carbazole-4-methane amide
Under 95 ℃, 0.45 gram (1.16mmol) embodiment 6 compounds and 5ml three normal-butyl hydride were heated 1 hour.Then, reaction mixture is added in the mixture of being made up of 125ml acetonitrile, 25ml tetrahydrofuran (THF) and 50ml acetate, and stirred 2 hours.With hexane extraction mixture 4 times, and resistates evaporated under vacuum condition; By recrystallization from acetone and hexane, obtain 0.30 gram title compound, yield is 60%.C
23H
24N
6O
3Ultimate analysis:
Calculated value: C63.88; H5.59; N19.43
Measured value: C64.06; H5.64; N19.28 preparation example 1 prepares 5-methoxycarbonyl-1 by 2-bromo-3-nitrobenzoic acid, 2-dihydro-2-methyl-9H-carbazole-4 (3H)-ketone
A) 2-bromo-3-nitrobenzoic acid methyl esters
At room temperature, with 2-bromo-3-nitrobenzoic acid (28.4g, 115.0mM), methyl iodide (18.0g, 127mM) and salt of wormwood (19.0g, the solution stirring that 137.4mM) in the 100ml dimethyl formamide, forms 72 hours; Again mixture is poured in 1.5 premium on currency.The precipitation that generates is collected by filtration, and dry under vacuum condition, obtain 28.79g (96%) 2-bromo-3-nitrobenzoic acid methyl esters white solid.
1H NMR (DMSO-d6) δ 8.3 (dd, 1H, J=1 and 8 Hz), 7.9 (dd, 1H, J=1 and 8 Hz), 7.7 (t, 1H, J=8 Hz), and 3.9 (s, 3H) .IR (KBr, cm
-1) 2950,1738,1541,1435,1364,1298, and1142.MS (FD) m/e 259,261.C
8H
6NO
4The Br ultimate analysis:
Calculated value: C36.95; H2.33; N5.39
Measured value: C37.14; H2.37; N5.45b) 2-bromo-3-Methyl anthranilate
Under the room temperature, with hydrogen feed by 2-bromo-3-nitrobenzoic acid methyl esters (020g, 0.77mM) and the solution that in the 25ml ethyl acetate, forms of 0.1g 3% sulfurized platinum/carbon 24 hours.Remove catalyzer by diatomite filtration, concentrated filtrate obtains 0.175g (99%) 2-bromo-3-Methyl anthranilate yellow oil.
1H NMR (CDCl
3) δ 7.15 (t, 1H, J=8 Hz), 7.1 (dd, 1H, J=1 and 8 Hz), 6.8 (dd, 1H, J=1 and 8 Hz), and 3.95 (s, 3H) .IR (CHCl
3, cm
-1) 3550,3380,2980,2900,1729,1613,1465,1451,1434,1324,1266, and 1025.MS (FD) m/e 230,232.C
8H
8NO
2The Br ultimate analysis:
Calculated value: C41.77; H3.51; N6.09
Measured value: C42.01; H3.29; N6.00c) 3-(3-methoxycarbonyl-2-bromobenzene amido)-5-methyl-cyclohexyl-2-alkene-1-ketone
Under 125 ℃, in nitrogen atmosphere, (10.2g, 44.3mM) with the 5-methyl isophthalic acid, (6.15g, 48.7mM) mixture of Zu Chenging is 1.5 hours for hydroresorcinol by 2-bromo-3-Methyl anthranilate in heating.The solid that generates is developed with ethyl acetate, obtained 9.98g (67%) 3-(3-methoxycarbonyl-2-bromobenzene amido)-5-methyl-cyclohexyl-2-alkene-1-ketone.
1H NMR (CDCl
3) δ 7.55 (m, 2H), 7.35 (dd, J=8 and 8 Hz, 1H), 6.4 (bs, 1H), 5.55 (s, 1H), 3.95 (s, 3H), 2.6-2.0 (m, 5H), 1.15 (3H) .MS (ES) m/e 338 for d, J=7 Hz, 340.d) 5-methoxycarbonyl-1,2-dihydro-2-methyl-9H-carbazole-4 (3H)-ketone
Will be by 3-(3-methoxycarbonyl-2-bromobenzene amido)-5-methyl-cyclohexyl-2-alkene-1-ketone (9.98g, 29.5mM), acid chloride (0.66g, 2.95mM), three-neighbour-tolylphosphine (1.8g, 5.9mM) and triethylamine (5.10ml, 36.6mM) suspension that forms in the 75ml acetonitrile heated 3 hours under reflux temperature.Under vacuum condition, remove and desolvate, again resistates is dissolved in methylene dichloride,, then, use anhydrous sodium sulfate drying, filter, and concentrate, obtain the 11g crude product with the saturated brine washing with 1N HCl washing.On silica gel,, obtain 5.7g (75%) 5-methoxycarbonyl-1,2-dihydro-2-methyl-9H-carbazole-4 (3H)-ketone by HPLC purifying (using the dichloromethane/ethyl acetate gradient elution).
1HNMR (CDCl
3) δ 9.5 (bs, 1H), 7.4 (d, J=8 Hz, 1H); 7.35 (d, J=8 Hz, 1H), 7.2 (dd, J=8 and 8 Hz; 1H), 4.0 (s, 3H), 2.9 (dd, J=13 and 4 Hz; 1H), 2.55 (m, 2H), 2.4 (m; 1H), 2.25 (dd, J=15 and 9 Hz, 1H); (1.05 d, J=7 Hz, 3H) .MS (ES) m/e226,258. embodiment 8{9-[(phenyl) methyl]-5-formamyl-2-methyl carbazole-4-yl } preparation of ethoxyacetic acid
A, 9-[(phenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, 2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1,2-dihydro-2-methyl-9H-carbazole-4 (3H)-ketone (2.0g, 7.77mM), bromotoluene (0.94g, 7.93mM) and salt of wormwood (2.15g, the suspension that 15.5mM) forms in 39ml DMF stirred 22 hours.With mixture with ethyl acetate and 1N HCl dilution, carry out layer separation after, use the ethyl acetate extraction water layer.Then, the ethyl acetate layer after merging is extracted secondary with 1N HCl, more once and once with saline water extraction with water extraction.Dry (Na
2SO
4) after, under vacuum condition, evaporate, obtain 2.61g (97%) 9-[(phenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, 2-dihydro carbazole-4 (3H)-ketone.
1H NMR (CDCl
3) δ 7.6-7.4 (m, 6H), 7.0 (m, 2H), 5.4 (s, 2H), 4.05 (s, 3H), 3.0 (m, 1H), 2.65-2.45 (m, 3H), 2.3 (dd, J=15 and 9 Hz, 1H), 1.1 (d, J=7Hz, 3H) .MS (ES) m/e 316,348.B, 9-[(phenyl) methyl]-2-methyl-4-hydroxy-5-methyl ester group carbazole
With the 9-[(phenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, (1.30g is 3.74mM) with 2 for 2-dihydro carbazole-4 (3H)-ketone, 3-two chloro-5,6-dicyano-1, (0.93g, 4.12mM) solution that forms in 37ml toluene stirred 5 hours between 80-90 ℃ the 4-benzoquinones.Mixture is passed through column chromatography purifying (using the methylene dichloride wash-out) on silica gel, obtains 270mg (21%) 9-[(phenyl) methyl]-2-methyl-4-hydroxy-5-methyl ester group carbazole.
1H NMR (CDCl
3) δ 10.45 (s, 1H), 8.0 (d, J=8 Hz, 1H); 7.55 (d, J=8 Hz, 1H), 7.4 (dd, J=8 and 8Hz; 1H), 7.3 (m, 3H), 7.05 (m; 2H), 6.65 (s, 1H), 6.6 (s; 1H), 5.5 (s, 2H), 4.1 (s; 3H), 2.45 (s, 3H) .MS (ES) m/e314,346.C, 9-[(phenyl) methyl]-2-methyl-4-hydroxyl-5-formamyl carbazole
Under 30-40 ℃, with the 9-[(phenyl) methyl]-(470mg, 1.36mM) solution in 20ml THF and the dense ammonium hydroxide water of 80ml carried out sonication 6 hours to 2-methyl-4-hydroxy-5-methyl ester group carbazole.The solid that is settled out is leached, and use Et
2The O development obtains 200mg (44%) 9-[(phenyl) methyl]-2-methyl-4-hydroxyl-5-formamyl carbazole.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (bs, 1H); 8.4 (bs, 1H), 7.75 (m, 1H); 7.4 (m, 2H), 7.25 (m, 3H); 7.1 (m, 2H), 6.95 (s, 1H); 6.45 (s, 1H), 5.65 (s, 2H); 2.4 (s, 3H) .MS (ES) m/e 314,331.D, the 9-[(phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Will be with the sodium hydride of 60% concentration in mineral oil (30.4mg 0.76mM) adds the 9-[(phenyl) methyl]-(202mg is 0.61mM) in the solution that forms in 21ml DMF and 4.6ml THF for 2-methyl-4-hydroxyl-5-formamyl carbazole.After 10 minutes, (77 μ l 0.482mM), and at room temperature stirred the mixture that generates 1.25 hours to add the monobromo-acetic acid methyl esters.With mixture with ethyl acetate dilution with wash with water.Use the ethyl acetate extraction water layer again.Organic layer after merging is extracted with saturated brine, use dried over sodium sulfate, filter and concentrate.Then, with resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 184mg (75%) the 9-[(phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl the ethoxyacetic acid methyl esters.
1H NMR (DMSO-d6) δ 7.55 (d, 1H, J=8Hz), 7.5 (bs, 1H), 7.4-7.15 (m, 9H), 6.45 (s, 1H), 5.7 (s, 2H), 4.9 (s, 2H), 3.75 (s, 3H), 2.4 (s, 3H) .MS (FD) m/e386,403.C
24H
22N
2O
4Ultimate analysis:
Calculated value: C71.63; H5.51; N6.96
Measured value: C71.74; H5.81; N6.69E, the 9-[(phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } ethoxyacetic acid
Under 25 ℃, will the 9-[(phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (83.5mg, 0.207mM) and the solution stirring that in 10ml ethanol, forms of 1.0ml (2.0mM) 2N sodium hydroxide 45 minutes.Gather up the white precipitate of generation by filtration, dry under vacuum condition then with the small amount of ethanol washing, obtain 48mg (56%) the 9-[(phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.MS(ES)m/e?314，372，389，411。It is 1 that filtrate is acidified to pH with 1N HCl.After being cooled to 5 ℃, gather up the white precipitate of generation, wash with water by filtration, dry under vacuum condition then, obtain 24mg (29%) the 9-[(phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl ethoxyacetic acid.
1H NMR (DMSO-d6) δ 11.2 (bs, 1H), 7.8 (bs, 1H), 7.6 (d, J=8 Hz, 1H), 7.45 (bs, 1H), 7.4-7.05 (m, 8H), 6.45 (s, 1H), 5.65 (s, 2H), 4.9 (s, 2H), 2.4 (s, 3H) .MS (ES) m/e 314,372,389.C
23H
20N
2O
4Ultimate analysis:
Calculated value: C71.12; H5.19; N7.21
Measured value: C71.33; H5.47; N7.19 embodiment 9{9-[(3-fluorophenyl) methyl]-5-formamyl-2-methyl carbazole-4-yl } preparation of ethoxyacetic acid
A, 9-[(3-fluorophenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, 2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1,2-dihydro-2-methyl-9H-carbazole-4 (3H)-ketone (1.0g, 3.89mM), the 3-fluoro benzyl bromide (0.48ml, 3.97mM) and salt of wormwood (1.07g, the suspension that 7.78mM) forms in 20ml DMF stirred 22 hours.With mixture with ethyl acetate and 1N HCl dilution, carry out layer separation after, use the ethyl acetate extraction water layer.Then, with the ethyl acetate layer after merging earlier with 1N HCl, again water, use saline water extraction at last.Dry (Na
2SO
4) after, under vacuum condition, evaporate, obtain 1.38g (97%) 9-[(3-fluorophenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, 2-dihydro carbazole-4 (3H)-ketone.
1H NMR (CDCl
3) δ 7.4-7.2 (m, 5H), 7.0 (m, 1H), 6.75 (m, 2H), 5.4 (s, 2H), 4.05 (s, 3H), 3.0 (m, 1H), 2.65-2.45 (m, 3H), 2.3 (dd, J=15 and 9 Hz, 1H), 1.1 (d, J=7 Hz, 3H) .MS (ES) m/e 334,366.B, 9-[(3-fluorophenyl) methyl]-2-methyl-4-hydroxy-5-methyl ester group carbazole
With the 9-[(3-fluorophenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, (1.37g is 3.75mM) with 2 for 2-dihydro carbazole-4 (3H)-ketone, 3-two chloro-5,6-dicyano-1, (0.94g, 4.13mM) solution that forms in 38ml toluene stirred 3 hours between 80-90 ℃ the 4-benzoquinones.Mixture is passed through column chromatography purifying (using the methylene dichloride wash-out) on silica gel, obtains 0.33g (24%) 9-[(3-fluorophenyl) methyl]-2-methyl-4-hydroxy-5-methyl ester group carbazole.
1H NMR (CDCl
3) δ 10.45 (s, 1H), 8.0 (d, J=8 Hz, 1H); 7.55 (d, J=8 Hz, 1H), 7.4 (dd, J=8 and 8 Hz; 1H), 7.3 (m, 2H), 6.95 (m, 1H); 6.85 (d, J=8 Hz, 1H), 6.75 (m, 1H); 6.65 (s, 1H), 5.5 (s, 2H), 4.1 (s; 3H), 2.45 (s, 3H) .MS (ES) m/e 332,364.C, 9-[(3-fluorophenyl) methyl]-2-methyl-4-hydroxyl-5-formamyl carbazole
Under 30-40 ℃, with the 9-[(3-fluorophenyl) methyl]-(0.33g, 0.91mM) solution in 14ml THF and the dense ammonium hydroxide water of 54ml carried out sonication 6.5 hours to 2-methyl-4-hydroxy-5-methyl ester group carbazole.The solid that is settled out is leached, wash with water, and use 35ml Et
2The O development obtains 182mg (57%) 9-[(3-fluorophenyl) methyl]-2-methyl-4-hydroxyl-5-formamyl carbazole.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (bs, 1H), 8.4 (bs; 1H), 7.75 (m, 1H), 7.4 (m, 2H); 7.25 (m, 1H), 7.05 (m, 1H); 6.9 (m, 2H), 6.85 (d, J=8 Hz; 1H), 6.45 (s, 1H), 5.65 (s; 2H), 2.4 (s, 3H) .MS (ES) m/e 332,349.D, the 9-[(3-fluorophenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Will be with the sodium hydride of 60% concentration in mineral oil (25.9mg 0.65mM) adds the 9-[(3-fluorophenyl) methyl]-2-methyl-4-hydroxyl-5-formamyl carbazole (181mg, 0.52mM) solution that in 18ml DMF and 3.9ml THF, forms.After 10 minutes, (66 μ l 0.70mM), and at room temperature stirred the mixture that generates 1.25 hours to add the monobromo-acetic acid methyl esters.With mixture with ethyl acetate dilution with wash with water.Use the ethyl acetate extraction water layer again.Organic layer after merging is extracted with saturated brine, use dried over sodium sulfate, filter and concentrate.Then, with resistates on silica gel by column chromatography purifying (with methylene dichloride/acetone gradient elution), obtain 170mg (78%) the 9-[(3-fluorophenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl the ethoxyacetic acid methyl esters.
1H NMR (DMSO-d6) δ 7.55 (d, 1H, J=8 Hz), 7.5 (bs, 1H), 7.4-7.25 (m, 2H), 7.2 (bs, 1H), 7.05 (m, 3H), 6.95 (d, J=8 Hz, 1H), 6.9 (d, J=8 Hz), 6.45 (s, 1H), 5.65 (s, 2H), 4.9 (s, 2H), 3.75 (s, 3H), 2.4 (s, 3H) .MS (FD) m/e 404,421.C
24H
21FN
2O
4Ultimate analysis:
Calculated value: C68.56; H5.03; N6.66
Measured value: C67.75; H4.95; N6.33E, the 9-[(3-fluorophenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } ethoxyacetic acid
Under 25 ℃, will the 9-[(3-fluorophenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (68.3mg, 0.162mM) and the solution stirring that in 8.1ml ethanol, forms of 0.81ml (1.6mM) 2N sodium hydroxide 30 minutes.Gather up the white precipitate of generation by filtration, dry under vacuum condition then with the small amount of ethanol washing, obtain 11mg (16%) the 9-[(3-fluorophenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.It is 2 that filtrate is acidified to pH with 1N HCl.After being cooled to 5 ℃, gather up the white precipitate of generation, wash with water by filtration, dry under vacuum condition then, obtain 31mg (47%) the 9-[(3-fluorophenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl ethoxyacetic acid.
1H NMR (DMSO-d6) δ 7.75 (bs, 1H), 7.6 (d, 1H, J=8 Hz), 7.45 (bs, 1H), 7.4-7.25 (m, 2H), 7.05 (m, 3H), 6.95 (d, J=8 Hz, 1H), 6.9 (d, J=8 Hz, 1H), 6.45 (5,1H), 5.65 (s, 2H), 4.8 (s, 2H), 2.4 (s, 3H) .MS (ES) m/e 390,407. recrystallization from acetone/hexane obtains analytic sample: C
23H
19FN
2O
4Ultimate analysis:
Calculated value: C67.97; H4.71; N6.89
Measured value: C68.21; H4.93; N7.16 embodiment 10{9-[(3-aminomethyl phenyl) methyl]-5-formamyl-2-methyl carbazole-4-yl } preparation of ethoxyacetic acid
A, 9-[(3-aminomethyl phenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, 2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1,2-dihydro-2-methyl-9H-carbazole-4 (3H)-ketone (1.0g, 3.89mM), 3-methyl-benzyl bromine (0.54ml, 3.97mM) and salt of wormwood (1.07g, the suspension that 7.78mM) forms in 20ml DMF stirred 19 hours.With mixture with ethyl acetate and 1N HCl dilution, carry out layer separation after, use the ethyl acetate extraction water layer.Then, with the ethyl acetate layer after merging earlier with 1N HCl, again water, use saline water extraction at last.Dry (Na
2SO
4) after, under vacuum condition, evaporate, obtain 1.41g (100%) 9-[(3-aminomethyl phenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, 2-dihydro carbazole-4 (3H)-ketone.
1H NMR (CDCl
3) δ 7.4-7.05 (m, 6H), 6.8 (m, 1H), 5.3 (s, 2H), 4.05 (s, 3H), 3.0 (m, 1H), 2.7-2.3 (m, 4H), 2.3 (s, 1H), 1.2 (d, J=7 Hz, 3H) .MS (ES) m/e 362.B, 9-[(3-aminomethyl phenyl) methyl]-2-methyl-4-hydroxy-5-methyl ester group carbazole
Will be with the sodium hydride of 60% concentration in mineral oil (0.36g 8.95mM) adds the 9-[(3-aminomethyl phenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, 2-dihydro carbazole-4 (3H)-ketone (1.41g, 3.89mM) solution in the 13ml diox.Stirred reaction mixture 6 minutes, then add the benzene sulfinic acid methyl esters (0.81ml, 6.22mM).The reaction mixture restir after 6 hours, is diluted with 20ml diox and 0.51ml acetate.Mixture was refluxed 30 minutes, with the ethyl acetate dilution, and with saturated sodium bicarbonate, salt solution, use water extraction again.Dry (Na
2SO
4) after, under vacuum condition, evaporate, obtain the 2.30g crude product.Again mixture is passed through column chromatography purifying (with toluene/methylene dichloride wash-out) on silica gel, obtains 0.92g (66%) 9-[(3-aminomethyl phenyl) methyl]-2-methyl-4-hydroxy-5-methyl ester group carbazole.
1H NMR (CDCl
3) δ 10.45 (s, 1H), 8.0 (d, J=8 Hz; 1H), 7.55 (d, J=8 Hz, 1H); 7.4 (dd, J=8 and 8 Hz, 1H), 7.4 (dd; J=8 and 8 Hz, 1H), 7.05 (d, J=8 HZ; 1H), 6.9 (s, 1H), 6.85 (d; J=8 Hz, 1H), 6.75 (s; 1H), 6.7 (s, 1H); 5.45 (s, 2H), 4.1 (s; 3H), 2.4 (s, 3H); 2.25 (s, 3H). MS (ES) m/e 328,360.C, 9-[(3-aminomethyl phenyl) methyl]-2-methyl-4-hydroxyl-5-formamyl carbazole
Under 30-40 ℃, with the 9-[(3-aminomethyl phenyl) methyl]-(0.92g, 2.56mM) solution in 38ml THF and the dense ammonium hydroxide water of 154ml carried out sonication 6 hours to 2-methyl-4-hydroxy-5-methyl ester group carbazole.The solid that is settled out is leached, washes with water, obtain 0.55g (63%) 9-[(3-aminomethyl phenyl) methyl]-2-methyl-4-hydroxyl-5-formamyl carbazole.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (bs, 1H), 8.4 (bs, 1H); 7.75 (m, 1H), 7.4 (m, 2H), 7.15 (dd; J=8 and 8Hz, 1H), 7.05 (m, 1H), 7.0 (s; 1H), 6.9 (s, 1H), 6.8 (d, J=8Hz; 1H), 6.45 (s, 1H), 5.65 (s, 2H); 2.4 (s, 3H), 2.2 (s, 3H) .MS (ES) m/e 328,345.D, the 9-[(3-aminomethyl phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Will be with the sodium hydride of 60% concentration in mineral oil (79.8mg 2.0mM) adds the 9-[(3-aminomethyl phenyl) methyl]-(0.55g is 1.60mM) in the solution that forms in 56ml DMF and 12ml THF for 2-methyl-4-hydroxyl-5-formamyl carbazole.After 10 minutes, (0.20ml 2.16mM), and at room temperature stirred the mixture that generates 1 hour to add the monobromo-acetic acid methyl esters.With mixture with ethyl acetate dilution with wash with water.Use the ethyl acetate extraction water layer again.Organic layer after merging is extracted with saturated brine, use dried over sodium sulfate, filter and concentrate.Then, with resistates on silica gel by column chromatography purifying (with methylene dichloride/acetone gradient elution), obtain 0.51g (76%) the 9-[(3-aminomethyl phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl the ethoxyacetic acid methyl esters.
1H NMR (DMSO-d6) δ 7.5 (m, 2H), 7.35 (dd, J=8 and 8 Hz, 1H), 7.2-7.1 (m, 2H), 7.05-6.95 (m, 4H), 6.85 (d, J=8 Hz, 1H), 6.45 (s, 1H), 5.6 (s, 2H), 4.9 (s, 2H), 3.75 (s, 3H), 2.4 (s, 3H), 2.2 (s, 3H) .MS (FD) m/e 400,417.C
25H
24N
2O
4Ultimate analysis:
Calculated value: C72.10; H5.81; N6.73
Measured value: C71.94; H5.71; N6.96E, the 9-[(3-aminomethyl phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } ethoxyacetic acid
Under 25 ℃, will the 9-[(3-aminomethyl phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (0.12g, 0.288mM) and the solution stirring that in 14ml ethanol, forms of 1.4ml (2.8mM) 2N sodium hydroxide 30 minutes.It is 2 that filtrate is acidified to pH with 1N HCl.Stir after 1 hour, gather up the white precipitate of generation, wash with water by filtration, dry under vacuum condition then, obtain 114mg (95%) the 9-[(3-aminomethyl phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl ethoxyacetic acid.
1H NMR (DMSO-d6) δ 11.1 (bs, 1H), 7.75 (bs, 1H), 7.6 (d, J=8 Hz, 1H), 7.45 (bs, 1H), 7.35 (dd, J=8 and 8Hz, 1H), 7.2-7.0 (m, 5H), 6.85 (d, J=8Hz, 1H), 6.45 (s, 1H), 5.6 (s, 2H), 4.8 (s, 2H), 2.4 (s, 3H), 2.2 (s, 3H) .MS (ES) m/e 386,403. recrystallization from acetone/hexane obtains analytic sample: C
24H
22N
2O
4Ultimate analysis:
Calculated value: C71.63; H5.51; N6.96
Measured value: C71.88; H5.65; N7.20 preparation example 2 prepares 5-methoxycarbonyl-1 by 2-bromo-3-nitrobenzoic acid, 2-dihydro-2-(4-trifluoromethyl)-9H-carbazole-4 (3H)-ketone
A) 2-bromo-3-nitrobenzoic acid methyl esters
At room temperature, with 2-bromo-3-nitrobenzoic acid (28.4g, 115.0mM), methyl iodide (18.0g, 127mM) and salt of wormwood (19.0g, the solution stirring that 137.4mM) in the 100ml dimethyl formamide, forms 72 hours; Again mixture is poured in 1.5 premium on currency.The precipitation that generates is collected by filtration, and dry under vacuum condition, obtain 28.79g (96%) 2-bromo-3-nitrobenzoic acid methyl esters white solid.
1H NMR (DMSO-d6) δ 8.3 (dd, 1H, J=1 and 8 Hz), 7.9 (dd, 1H, J=1 and8 Hz), 7.7 (t, 1H, J=8 Hz), and 3.9 (s, 3H) .IR (KBr, cm
-1) 2950,1738,1541,1435,1364,1298, and 1142.MS (FD) m/e259,261.C
8H
6NO
4The Br ultimate analysis:
Calculated value: C36.95; H2.33; N5.39
Measured value: C37.14; H2.37; N5.45b) 2-bromo-3-Methyl anthranilate
Under the room temperature, with hydrogen feed by 2-bromo-3-nitrobenzoic acid methyl esters (0.20g, 0.77mM) and the solution that in the 25ml ethyl acetate, forms of 0.1g 3% sulfurized platinum/carbon 24 hours.Remove catalyzer by diatomite filtration, concentrated filtrate obtains 0.175g (99%) 2-bromo-3-Methyl anthranilate yellow oil.
1H NMR (CDCl
3) δ 7.15 (t, 1H, J=8 Hz), 7.1 (dd, 1H, J=1 and 8 Hz), 6.8 (dd, 1H, J=1 and 8 Hz), and 3.95 (s, 3H) .IR (CHCl
3, cm
-1) 3550,3380,2980,2900,1729,1613,1465,1451,1434,1324,1266, and 1025.MS (FD) m/e 230,232.C
8H
8NO
2The Br ultimate analysis:
Calculated value: C41.77; H3.51; N6.09
Measured value: C42.01; H3.29; N6.00c) 3-(3-methoxycarbonyl-2-bromobenzene amido)-5-(4-trifluoromethyl)-hexamethylene-2-alkene-1-ketone
Under 150 ℃, in nitrogen atmosphere, the heating by 2-bromo-3-Methyl anthranilate (10.2g, 44.3mM) and 5-(4-trifluoromethyl)-hydroresorcinol (1.77g, 6.93mM) mixture of Zu Chenging is 20 minutes.The solid that generates is developed with 4: 1 ethylacetate/ether, obtained 2.18g (74%) 3-(3-methoxycarbonyl-2-bromobenzene amido)-5-(4-trifluoromethyl)-hexamethylene-2-alkene-1-ketone.
1H NMR (DMSO-d6) δ 8.9 (s, 1H), 7.75-7.5 (m, 7H), 3.9 (s, 3H), 3.5 (m, 1H), 2.9 (dd, J=14 and 9 Hz, 1H), 2.7 (dd, J=14 and 4 Hz, 1H), 2.55 (dd, J=14 and 9 Hz, 1H), 2.35 (dd, J=14 and 4 Hz, 1H) .MS (ES) .m/e 368,370.d) 5-methoxycarbonyl-1,2-dihydro-2-(4-trifluoromethyl)-9H-carbazole-4 (3H)-ketone
Will be by 3-(3-methoxycarbonyl-2-bromobenzene amido)-5-(4-trifluoromethyl)-hexamethylene-2-alkene-1-ketone (2.18g, 4.66mM), acid chloride (0.10g, 0.47mM), three-neighbour-tolylphosphine (0.28g, 0.93mM) and triethylamine (0.8ml, 5.78mM) suspension that forms in the 12ml acetonitrile heated 3 hours under reflux temperature.Under vacuum condition, remove and desolvate, again resistates is dissolved in methylene dichloride,, then, use anhydrous sodium sulfate drying, filter, and concentrate, obtain the 2.21g crude product with the saturated brine washing with 1N HCl washing.On silica gel,, obtain 1.57g (87%) 5-methoxycarbonyl-1,2-dihydro-2-(4-trifluoromethyl)-9H-carbazole-4 (3H)-ketone by HPLC purifying (using the dichloromethane/ethyl acetate gradient elution).
1H NMR (CDCl
3) δ 9.2 (bs, 1H), 7.6 (d; J=8 Hz, 2H), 7.45-7.35 (m; 5H), 7.25 (d, J=8 Hz; 2H), 3.55 (m, 1H); 3.2-3.0 (m, 2H), 2.7 (m; 2H) .MS. (ES) m/e 356,388. embodiment 11{9-[(phenyl) methyl]-5-formamyl-2-(4-trifluoromethyl)-carbazole-4-yl } preparation of ethoxyacetic acid
A) methyl 9-[(phenyl)]-5-methoxycarbonyl-2-(4-trifluoromethyl)-1,2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1, and 2-dihydro-2-(4-trifluoromethyl)-9H-carbazole-4 (3H)-ketone (1.57g, 4.05mM), bromotoluene (0.49g, 4.13mM) and salt of wormwood (1.12g, the suspension that 8.10mM) in 20ml DMF, forms stirring 22 hours.With mixture with ethyl acetate and 1N HCl dilution, carry out layer separation after, use the ethyl acetate extraction water layer.Then, with the ethyl acetate layer after merging with 1N HCl, water, then use saline water extraction.Dry (Na
2SO
4) after, under vacuum condition, evaporate, obtain 1.87g (96%) 9-[(phenyl) methyl]-5-methoxycarbonyl-2-(4-trifluoromethyl)-1,2-dihydro carbazole-4 (3H)-ketone.
1H NMR (CDCl
3) δ 7.6 (d, J=8 Hz, 2H), 7.45-7.25 (m, 8H), 6.95 (m, 2H), 5.35 (s, 2H), 4.05 (s, 3H), 3.65 (m, 1H), 3.2 (dd, J=16 and 5 Hz, 1H), 3.0 (dd, J=16 and 10 Hz, 1H), methyl 2.8 (m, 2H) .MS (ES) m/e 478.b) 9-[(phenyl)]-2-(4-trifluoromethyl)-4-hydroxy-5-methyl ester group carbazole
With the 9-[(phenyl) methyl] 5-methoxycarbonyl-2-(4-trifluoromethyl)-1, (1.87g is 3.92mM) with 2 for 2-dihydro carbazole-4 (3H)-ketone, 3-two chloro-5,6-dicyano-1, (0.89g, the solution that 3.92mM) forms in 39ml toluene refluxed 25 minutes the 4-benzoquinones.Mixture is passed through column chromatography purifying (using the toluene wash-out) on silica gel, obtains 1.10g (59%) 9-[(phenyl) methyl]-2-(4-trifluoromethyl)-4-hydroxy-5-methyl ester group carbazole.
1H NMR (CDCl
3) δ 10.65 (s, 1H), 8.05 (d, J=8 Hz; 1H), 7.8 (m, 3H), 7.65 (m; 3H), 7.6 (d, J=8 Hz, 1H); 7.45 (dd, J=8 and 8 Hz, 1H), 7.3-7.1 (m; 2H), 5.6 (s, 2H); (4.1 s, 3H) .MS (ES) m/e 444,476.c) 9-[(phenyl) methyl]-2-(4-trifluoromethyl)-4-hydroxyl-5-formamyl carbazole
Under 30-40 ℃, with the 9-[(phenyl) methyl]-(1.10g, 2.31mM) solution in 35ml THF and the dense ammonium hydroxide water of 140ml carried out sonication 6 hours to 2-(4-trifluoromethyl)-4-hydroxy-5-methyl ester group carbazole.The solid that is settled out is leached and washes with water.Use Et earlier
2O uses 2: 1Et again
2O/CH
2Cl
2Development obtains 0.20g (19%) 9-[(phenyl) methyl]-2-(4-trifluoromethyl)-4-hydroxyl-5-formamyl carbazole.
1HNMR (DMSO-d6) δ 10.8 (s, 1H), 8.9 (bs, 1H); 8.45 (bs, 1H), 8.0 (d, J=8 Hz; 2H), 7.8 (d, J=8 Hz, 2H); 7.6 (s, 1H), 7.5 (m, 2H); 7.3-7.1 (m, 6H), 7.0 (s, 1H); 5.8 (s, 2H) .MS (ES) m/e 444,461.d) the 9-[(phenyl) methyl]-2-(4-trifluoromethyl)-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Will be with the sodium hydride of 60% concentration in mineral oil (22mg 0.54mM) adds the 9-[(phenyl) methyl]-(0.20g is 0.43mM) in the solution that forms in 15ml DMF and 3ml THF for 2-(4-trifluoromethyl)-4-hydroxyl-5-formamyl carbazole.After 7 minutes, (56 μ l 0.59mM), and at room temperature stirred the mixture that generates 1 hour to add the monobromo-acetic acid methyl esters.With mixture with ethyl acetate dilution with wash with water.Use the ethyl acetate extraction water layer again.Organic layer after merging is extracted with saturated brine, use dried over sodium sulfate, filter and concentrate.Then, with resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 0.19g (84%) the 9-[(phenyl) methyl]-2-(4-trifluoromethyl)-5-formamyl carbazole-4-yl the ethoxyacetic acid methyl esters.
1H NMR (DMSO-d6) δ 8.0 (d, J=8 Hz, 2H), 7.85 (d, J=8 Hz, 2H), 7.7 (s, 1H), 7.6 (d, J=8 Hz, 1H), 7.6 (bs, 1H), 7.4 (dd, J=8 and 8 Hz, 1H), and 7.3-7.1 (m, 6H), 7.1 (d, J=8 Hz, 1H), 7.0 (s, 1H), 5.8 (s, 2H), 5.1 (s, 2H), 3.7 (s, 3H) .MS (FD) m/e 516,533.C
30H
23F
3N
2O
4Ultimate analysis:
Calculated value: C67.66; H4.36; N5.26
Measured value: C68.38; H4.29; N5.67e) the 9-[(phenyl) methyl]-2-(4-trifluoromethyl)-5-formamyl carbazole-4-yl } ethoxyacetic acid
Under 25 ℃, will the 9-[(phenyl) methyl]-2-(4-trifluoromethyl)-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (101mg, 0.19mM) and the solution stirring that in 9.5ml ethanol, forms of 0.95ml (1.9mM) 2N sodium hydroxide 30 minutes.It is 2 that reaction mixture is acidified to pH with 1N HCl.Stir after 30 minutes, gather up the white precipitate of generation, wash with water by filtration, dry under vacuum condition then, obtain 73mg (75%) the 9-[(phenyl) methyl]-2-(4-trifluoromethyl)-5-formamyl carbazole-4-yl ethoxyacetic acid.
1H NMR (DMSO-d6) δ 11.0 (bs, 1H), 8.0 (d, J=8 Hz, 2H), 7.85 (d, J=8 Hz, 2H), 7.8 (bs, 1H), 7.7 (s, 1H), 7.65 (d, J=8 Hz, 1H), 7.4 (m, 2H), 7.3-7.1 (m, 6H), 7.0 (s, 1H), 5.8 (s, 2H), 5.0 (s, 2H) .MS (ES) m/e 502,519.C
29H
21F
3N
2O
4Ultimate analysis:
Calculated value: C67.17; H4.09; N5.40
Measured value: C67.05; H4.11; N5.31 embodiment 129-benzyl-5-(2-methanesulfonamido) oxyethyl group-7-methoxyl group-1,2,3, preparation A, the 5-of 4-tetrahydro carbazole-4-methane amide (2-amino) oxyethyl group-9-benzyl-7-methoxyl group-1,2,3, the preparation of 4-tetrahydro carbazole-4-methane amide
Under 0 ℃, dropwise (53 μ l 0.97mmol) added the solution that 1.93ml (1.93mmol) 1M lithium aluminum hydride/THF forms in 13ml THF in 5 minutes with sulfuric acid.At room temperature, mixture was stirred 1 hour, then dropwise add 9-benzyl-7-methoxyl group-5-cyano group methoxyl group-1 so that temperature keeps below 26 ℃ speed, 2,3,4-tetrahydro carbazole-4-methane amide (0.50g, 1.29mmol) solution that in 13ml THF, forms.After 45 minutes, will react earlier with 1: 1 THF/H of 0.5ml
2O uses 0.75ml 13%NaOH again, uses 80 μ l H at last
2The Ok stopped reaction; Then, with ethyl acetate and saturated sodium bicarbonate dilution, and carry out layer and separate.With the organic layer saline water extraction, use dried over sodium sulfate, and under vacuum condition, evaporate.With resistates chromatogram on silica gel, with 9: 1: 0.1 CH
2Cl
2/ MeOH/NH
4The OH wash-out obtains subhead product (0.28g, 55%).MS (ES+) 394B, 9-benzyl-5-(2-methanesulfonamido) oxyethyl group-7-methoxyl group-1,2,3, the preparation of 4-tetrahydro carbazole-4-methane amide
Under 0 ℃, in the 10ml THF solution of 0.20g (0.51mmol) A step products, add triethylamine (71 μ l, 0.5lmmol) and methylsulfonyl chloride (39 μ l, 0.51mmol).At 0 ℃ after following 40 minutes, will react with ethyl acetate and saturated sodium bicarbonate dilution, and carry out layer separation.With the organic layer saline water extraction, use dried over sodium sulfate, and under vacuum condition, evaporate.Then, with resistates chromatogram on silica gel, with 20: 1 CH
2Cl
2/ MeOH wash-out, and crystallization from ethyl acetate/hexane obtain title product (0.13g, 54%).MS (ES+) 472C
24H
29N
3O
5The S ultimate analysis:
Calculated value: C61.13; H6.20; N8.91
Measured value: C61.04; H6.16; The preparation of preparation A, 4-(2-amino) oxyethyl group-9-benzyl-2-methoxyl group carbazole-5-methane amide of N9.21 embodiment 139-benzyl-4-(2-methanesulfonamido) oxyethyl group-2-methoxyl group carbazole-5-methane amide
Under 0 ℃, dropwise (34.5 μ l 0.63mmol) added the solution that 1.25ml (1.25mmol) 1M lithium aluminum hydride/THF forms in 8.3ml THF in 5 minutes with sulfuric acid.At room temperature, mixture was stirred 1 hour, then dropwise add 9-benzyl-4-cyano group methoxyl group-2-methoxyl group carbazole-5-methane amide (0.32g, 0.83mmol) suspension that in 8.3ml THF, forms so that temperature keeps below 26 ℃ speed.After 45 minutes, will react earlier with 1: 1 THF/H of 0.32ml
2O uses 0.48ml 13%NaOH again, uses 51 μ l H at last
2The O stopped reaction; Then, with ethyl acetate and saturated sodium bicarbonate dilution, and carry out layer and separate.With the organic layer saline water extraction, use dried over sodium sulfate, and under vacuum condition, evaporate.With resistates chromatogram on silica gel, with 9: 1: 0.1CH
2Cl
2/ MeOH/NH
4The OH wash-out obtains subhead product (148mg, 46%).The preparation of MS (ES+) 390B, 9-benzyl-4-(2-methanesulfonamido) oxyethyl group-2-methoxyl group carbazole-5-methane amide
Under 0 ℃, in the 107mg in 11ml THF (0.27mmol) A step products, add triethylamine (38 μ l, 0.27mmol) and methylsulfonyl chloride (21 μ l, 0.27mmol).At 0 ℃ after following 40 minutes, will react with ethyl acetate and saturated sodium bicarbonate dilution, and carry out layer separation.With the organic layer saline water extraction, use dried over sodium sulfate, and under vacuum condition, evaporate.Then, with resistates chromatogram on silica gel, with 10: 1 CH
2Cl
2/ acetone wash-out, and crystallization from ethyl acetate/hexane obtain title product (28.6mg, 22%).MS (ES+) 468C
24H
25N
3O
5The S ultimate analysis:
Calculated value: C61.66; H5.39; N8.99
Measured value: C61.52; H5.31; The preparation of N8.81 embodiment 149-benzyl-4-(2-fluoroform sulfonamido) oxyethyl group-2-methoxyl group carbazole-5-methane amide
Under 0 ℃, in the A step products of the 31.2mg in 3.2ml THF (0.08mmol) embodiment 13, add triethylamine (11.1 μ l, 0.08mmol) and trifluoromethanesulfchloride chloride (8.5 μ l, 0.08mmol).At 0 ℃ after following 40 minutes, will react with ethyl acetate and saturated sodium bicarbonate dilution, and carry out layer separation.With the organic layer saline water extraction, use dried over sodium sulfate, and under vacuum condition, evaporate.Then, with resistates chromatogram on silica gel, use CH
2Cl
2/ ethyl acetate gradient elution, and, obtain title product (19.3mg, 46%) with the ether development.MS (ES+) 522C
24H
22F
3N
3O
5The S ultimate analysis:
Calculated value: C55.27; H4.25; N8.06
Measured value: C55.11; H4.40; N7.99 embodiment 159-benzyl-5-methanesulfonamido methoxyl group-7-methoxyl group-1,2,3, the preparation of 4-tetrahydro carbazole-4-methane amide
In the 51mg in 25ml THF (0.125mmol) (9-benzyl-4-formamyl-7-methoxyl group-1,2,3,4-tetrahydro carbazole-5-yl) ethoxyacetic acid, add carbonyl dimidazoles (20.2mg, 0.125mmol).To react and reflux 21 hours, then be cooled to room temperature.(11.9mg, 0.125mmol) (18.7 μ l, the mixture that 0.125mmol) forms in 2.5ml THF adds wherein with the diazabicylo undecylene with Toluidrin again.3.5 after hour, will react with the ethyl acetate dilution, and extract respectively with 10% sodium bisulfite, saturated sodium bicarbonate, 10% sodium bisulfite and salt solution respectively.With the organic layer dried over sodium sulfate, and under vacuum condition, evaporate.Then, with resistates chromatogram on silica gel,, obtain title product (8mg, 10%) with methylene dichloride/ethanol gradient elution.C
24H
27N
3O
6S high resolution MS:
Calculated value: 485.1621
Measured value: the preparation of 485.1625 embodiment 169-benzyls-4-methanesulfonamido methoxyl group carbazole-5-methane amide
To the 48mg in 26ml THF (0.13mmol) (9-benzyl-4-formamyl carbazole-4-yl) ethoxyacetic acid add carbonyl dimidazoles (21mg, 0.13mmol).To react and reflux 25 hours, then be cooled to room temperature.(12mg, 0.13mmol) (19 μ l, the mixture that 0.13mmol) forms in 2.6ml THF adds wherein with the diazabicylo undecylene with Toluidrin again.After 3 hours, will react with ethyl acetate dilution, and earlier with 10% sodium bisulfite, use saline water extraction again.With the organic layer dried over sodium sulfate, and under vacuum condition, evaporate.Then, with resistates chromatogram on silica gel,, obtain impure product with methylene dichloride/ethanol gradient elution.Again it is extracted in the saturated sodium bicarbonate from ethyl acetate, and acidifying once more, title product (3.9mg, 6.7%) obtained.C
23H
21N
3O
5S high resolution MS:
Calculated value: 452.1280
Measured value: 452.1284 embodiment 17[5-formamyls-2-amyl group-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid
A, 5-amyl group hexamethylene-1, the preparation of 3-diketone and its enol mixture of isomers
Under the room temperature, in nitrogen atmosphere, (1.98g, (7.20g is 39.9mmol) at THF (20ml)/H 49.5mmol) to add olivetol with sodium hydroxide along with stirring
2The suspension of the formation among the O (20ml).With solution stirring until clarification.After removing stirring rod, add 5%Rh/Al
2O
3(500mg).Then, be to handle 17 hours in 60 pounds/square inch the Parr electromagnetic shaker mixture at hydrogen pressure.Behind diatomite filtration, filtrate is cooled to 0 ℃, then handle with 5N HCl (10.9ml).Under 40 ℃, mixture is evaporated under vacuum condition, and with resistates chromatogram (elder generation's 40-100% ethyl acetate/hexane on silica gel, back 0-15% methanol/ethyl acetate gradient elution), obtain with ratio is the subhead product white solid (4.80g, 66%) of ketone/alkanol isomer mixture form existence of 3: 2.
Mp 68.5-69.5 ℃; IR (KBr) 3200-2400 (br), 1610,1542cm
-1 1H NMR (CDCl
3) δ 0.88 (br t, J=6.6 Hz, 3H ,-CH
3), 3.38 (s, 2H, the ketone isomer-CH
2-), 4.13 (s, 1H, the enol isomer=CH-), 8.90 (br s, 1H ,-OH); ESIMS m/e 183. (M
++ 1); C
11H
18O
2Ultimate analysis:
Calculated value: C72.49; H9.95
Measured value: C72.72; H9.95B, 5-(hydroxymethyl) hexamethylene-1, the preparation of 3-diketone and its enol mixture of isomers
According to testing sequence as described in steps A, finish the synthetic of subhead compound with 75% yield.
IR (KBr) 3547,3453 (br), 1633,1580cm
-1 1H NMR (DMSO-d
6) δ 1.90-2.30 (m, 5H), 3.30 (br s, 2H ,-CH
2O-), 4.61 (br s, 1H ,-OH), 5.13 (s, 1H), 10.94 (s, 1H ,-OH); ESIMS m/e 143 (M
++ 1); C
7H
10O
3Ultimate analysis:
Calculated value: C59.14; H7.09
Measured value: C59.44; The preparation of H7.08C, 3-(2-bromo-3-methoxycarbonyl anilino)-5-amyl group hexamethylene-2-alkene-1-ketone
Under 150 ℃, under stirring condition, 3-amino-2-methyl-bromobenzoate (the 5.12g that will make by preparation example 4,22.3mmol) and A stepwise compound (4.06g, 22,3mmol) mixture of Zu Chenging heated in oil bath 1.4 hours, and this is reflected at and carries out under the positive nitrogen pressure to remove water vapour continuously.At room temperature, mixture chromatogram (with 3-100% ethyl acetate/hexane gradient elution) on silica gel is obtained subhead compound (6.06g, 69%) white solid.Mp132.0-134.0 ℃; IR (KBr) 3220 (br), 1726,1580cm
-1 1H NMR (CDCl
3) δ 0.90 (br t, J=6.6 Hz, 3H ,-CH
3), 1.25-1.45 (m, 8H), 2.05-2.27 (m, 2H), 2.35-2.57 (m, 3H), 3.94 (s, 3H ,-OCH
3), 5.57 (s, 1H ,=CH-), 6.44 (br s, 1H ,-NH), 7.35 (t, J=6.8 Hz, 1H), 7.53 (d, J=6.8 Hz, 2H); ESIMS m/e 394 (M
++ 1,
79Br), 396 (M
++ 1,
81Br) .D, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-amyl group-9H-carbazole-4 (3H)-ketone
Under the room temperature, in nitrogen atmosphere, along with stir with triethylamine (2.09ml, 15.0mmol) add above-mentioned C stepwise compound (3.94g, 10.0mmol), Pd (OAc)
2(338mg is 1.50mmol) with three-neighbour-tolylphosphine (914mg, 3.00mmol) suspension that forms in acetonitrile (40ml).Then, under 85 ℃, the mixture that generates was heated in oil bath 1 hour.Under 35 ℃, again mixture is evaporated under vacuum condition, and resistates chromatogram (with 20-100% ethyl acetate/hexane gradient elution) on silica gel is obtained subhead compound (2.45g, 78%) white solid.
Mp 116.0-117.5 ℃; IR (KBr) 3379 (br), 3180 (Br), 1725,1627cm
-1 1H NMR (CDCl
3) δ 0.89 (brt, J=6.6 Hz, 3H ,-CH
3), 1.20-1.47 (m, 8H), 2.20-2.32 (m, 2H), 2.50-2.67 (m, 2H), 2.92-3.05 (m, 1H), 4.02 (s, 3H ,-OCH
3), 7.18-7.26 (m, 1H), 7.35-7.43 (m, 2H), 9.20-9.42 (brs, 1H ,-NH); ESIMS m/e 314 (M
++ 1); C
19H
23NO
3Ultimate analysis:
Calculated value: C72.82; H7.40; N4.47
Measured value: C72.59; H7.43; N4.51E, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-amyl group-9-(phenyl methyl)-carbazole-4 (3H)-ketone
In nitrogen atmosphere, along with stir with bromotoluene (1.25ml, 10.5mmol) add embodiment 17D compound (3.00g, 9.57mmol) and salt of wormwood (1.98g is 14.4mmol) in dry DMF (30ml) in the suspension of formation.After the mixture that generates stirred 5 hours, under 40 ℃, mixture is evaporated under vacuum condition, and resistates chromatogram (with 10-60% ethyl acetate/hexane gradient elution) on silica gel is obtained subhead compound (3.28g, 85%) white solid.
Mp 119.0-120.5 ℃; IR (KBr) 1723,1650cm
-1 1H NMR (CDCl
3) δ 0.87 (br t, J=6.6 Hz, 3H ,-CH
3), 1.23-1.52 (m, 8H), 2.25-2.40 (m, 2H), 2.47-2.57 (m, 1H), 2.69 (d, J=12.8Hz, 1H), 2.99 (dd, J=16.6,3.6 Hz, 1H), 4.05 (s, 3H ,-OCH
3), 5.36 (s, 2H), 6.98-7.02 (m, 2H), 7.20-7.40 (m, 6H); ESIMS m/e 404 (M
++ 1) preparation of .F, 5-methoxycarbonyl-4-hydroxyl-2-amyl group-9-(phenyl methyl) carbazole
(a) by the DDQ oxidizing reaction: in nitrogen atmosphere, (563mg 2.48mmol) adds above-mentioned E stepwise compound (1.00g, 2.48mmol) suspension that forms in dry toluene (30ml) with DDQ to be accompanied by stirring.With the mixture heating up that generates to refluxing 25 minutes.At room temperature, mixture chromatogram (with 0-30% ethyl acetate/toluene gradient elution) on silica gel is obtained subhead compound (290mg, 29%) yellow solid (310mg, 31%).(b) by benzene sulfinic acid ester elimination reaction: in nitrogen atmosphere, (60% in mineral oil with sodium hydride to be accompanied by stirring, 192mg, 4.80mmol) the above-mentioned E stepwise compound (807mg of adding, 2.00mmol) and benzene sulfinic acid methyl esters (375mg, 2.40mmol) anhydrous 1, in the solution that forms in the 4-diox (10ml).Under 50 ℃, mixture was heated in oil bath 2 hours 15 minutes.Add 15ml 1 again, after the 4-diox diluted, (0.343ml 6.00mmol) handled, and the suspension that generates is heated to backflow 40 minutes with acetate with mixture.Under vacuum condition, evaporate this mixture, and resistates chromatogram (with 0-5% ethyl acetate/toluene gradient elution) on silica gel is obtained subhead compound (690mg, 86%) yellow solid.
Mp 130.0-132.0 ℃; IR (KBr) 3200 (br), 1686 cm
-1 1H NMR (CDCl
3) δ 0.87 (br t, J=6.6 Hz, 3H ,-CH
3), 1.25-1.38 (m, 4H), 1.60-1.75 (m, 2H), 2.69 (t, J=7.7 Hz, 2H), 4.10 (s, 3H ,-OCH
3), 5.52 (s, 2H), 6.71 (5,1H), 6.76 (s, 1H), 7.09-7.11 (m, 2H), 7.20-7.30 (m, 3H), 7.37 (t, J=8.0 Hz, 1H), 7.55 (d, J=8.0 Hz, 1H), 7.97 (d, J=8.0 Hz, 1H), 10.43 (s, 1H ,-OH); ESIMS m/e 402 (M
++ 1); C
26H
27NO
30.2 (C
7H
8) ultimate analysis:
Calculated value: C78.37; H6.86; N3.34
Measured value: C78.48; H6.68; The preparation of N3.53G, 5-formamyl-4-hydroxyl-2-amyl group-9-(phenyl methyl) carbazole
In the pressure bottle under-25 ℃, be accompanied by be stirred in above-mentioned F stepwise compound (590mg, 1.47mmol) in the suspension that in ammoniacal liquor (50ml)/THF (10ml), forms with ammonia bubbling 5 minutes.After bottle built with screw-cap, mixture was at room temperature stirred 3 days.After being cooled to-25 ℃, remove screw-cap, and mixture was at room temperature stirred 10 minutes.After concentrating, resistates chromatogram (with 0-40% tetrahydrofuran (THF)/toluene gradient elution) on silica gel and is obtained required subhead product (397mg, 70%) light yellow solid with recycling step F compound (160mg, 27%).IR (KBr) 3437,3200 (br), 1633,1601cm
-1 1H NMR (CDCl
3) δ 0.86 (br t, J=6.6 Hz, 3H ,-CH
3), 1.22-1.38 (m, 4H), 1.60-1.75 (m, 2H), 2.69 (t, J=7.7 Hz, 2H), 5.52 (s, 2H), 6.16 (s, 1H,-NH), 6.53 (s, 1H ,-NH), 6.72 (s, 1H), 6.76 (s, 1H), 7.07-7.11 (m, 2H), 7.23-7.30 (m, 3H), 7.35 (t, J=7.7 Hz, 1H), 7.43 (d, J=7.7 Hz, 1H), 7.48 (d, J=7.7 Hz, 1H), 9.80 (s, 1H ,-OH); ESIMS m/e 387 (M
++ 1); C
25H
26N
2O
2Ultimate analysis:
Calculated value: C77.69; H6.78; N7.25
Measured value: C77.69; H6.63; The preparation of N7.15H, [5-formamyl-2-amyl group-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid methyl esters
Under the room temperature, in nitrogen atmosphere, (48.0mg 0.314mmol) adds the foregoing description 17G compound (110mg with the monobromo-acetic acid methyl esters to be accompanied by stirring, 0.285mmol) and cesium carbonate (186mg is 0.570mmol) in the suspension that forms in dry DMF (2ml).The compound that generates was stirred 1 hour.After concentrating under 40 ℃ of vacuum conditions, resistates chromatogram (with 10-60% tetrahydrofuran (THF)/toluene gradient elution) on silica gel is obtained subhead product (115mg, 88%) white solid.
Mp 195.0-196.0 ℃; IR (KBr) 3365 (br), 3157 (br), 1758,1640cm
-1 1H NMR (CDCl
3) δ 0.87 (br t, J=6.6 Hz, 3H ,-CH
3), 1.22-1.35 (m, 4H), 1.58-1.70 (m, 2H), 2.69 (t, J=7.6 Hz, 2H), 3.84 (s, 3H ,-OCH
3), 4.89 (s, 2H ,-OCH
2-), 5.50 (s, 2H ,-NCH
2-), 5.95 (br s, 1H ,-NH), 6.08 (br s, 1H ,-NH), 6.41 (s, 1H), 6.85 (s, 1H), 7.07-7.11 (m, 2H), 7.23-7.40 (m, 6H); ESIMS m/e 459 (M
++ 1); C
28H
30N
2O
4Ultimate analysis:
Calculated value: C73.34; H6.59; N6.11
Measured value: C73.56; H6.43; The preparation of N6.25I, [5-formamyl-2-amyl group-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid
((110mg is 0.240mmol) at THF (2ml)/CH 0.360mmol) to add the foregoing description 17H compound for 4.17N, 86.3ml with lithium hydroxide to be accompanied by stirring
3OH (0.3ml)/H
2In the suspension that forms among the O (0.3ml).Under 55 ℃, the mixture that generates is stirred 30 minutes formation white suspension in oil bath.After 5 milliliters of THF were added this suspension, (96.0ml 0.480mmol) handled and generates settled solution with 5N HCl with it.After concentrating, white solid is suspended in THF (0.5ml)/H once more
2Among the O (5ml), carry out sonication, filter, and drying obtains subhead compound (106mg, 99%) white solid.
IR (KBr) 3458 (br), 3500-3100 (br), 1656,1620cm
-1 1H NMR (DMSO-d
6) δ 0.80 (br t, J=6.6 Hz, 3H ,-CH
3), 1.18-1.30 (m, 4H), 1.50-1.62 (m, 2H), 2.61 (br t, J=7.3Hz, 2H), 4.55. (s, 2H ,-OCH
2-), 5.60 (s, 2H ,-NCH
2-), 6.40 (s, 1H), 6.95-7.32 (m, 9H), 7.51 (d, J=8.0 Hz, 1H), 7.70 (br s, 1H ,-NH); ESIMS m/e 445 (M
++ 1). embodiment 18[5-formamyl-2-(1-methylethyl)-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid
A, 3-(2-bromo-3-methoxycarbonyl anilino)-5-[(1-methyl] ethyl] preparation of hexamethylene-2-alkene-1-ketone
The described method of C step by embodiment 17 makes the subhead compound with 70% yield.
Mp 129.0-130.0 ℃;
1H NMR (CDCl
3) δ 0.98 (t, J=5.5 Hz, 6H), 1.66 (m, 1H), 2.00 (m, 1H), 2.14 (t, J=14.8 Hz, 1H), 2.46 (m, 3H), 4.00 (s, 3H), 5.57 (s, 1H), 6.40 (br s, 1H), 7.35 (t, J=7.9 Hz, 1H), 7.35 (d, J=7.8 Hz, 2H); ESIMS m/e 366 (M
++ 1,
79Br), 368 (M
++ 1,
81Br) .B, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-(1-methylethyl)-9H-carbazole-4 (3H)-ketone
Make the subhead compound by the described method of embodiment 17D with 65% yield.Mp 175.0-177.0 ℃;
1H NMR (CDCl
3) δ 0.95 (t, J=6.7 Hz, 6H), 1.62 (m, 1H), 2.05 (m, 1H), 2.27 (dd, J=16.1,12.6 Hz, 1H), 2.60 (m, 2H), 2.89 (dd, J=16.4,4.3 Hz, 1H), 4.02 (s, 3H), 7.23 (m, 1H), 7.36 (m, 2H), 9.28 (br s, 1H); ESIMS m/e 286 (M
++ 1); C
17H
19NO
3Ultimate analysis:
Calculated value: C71.56; H6.71; N4.91
Measured value: C71.43; H6.62; N4.74C, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-(1-methylethyl)-9-(phenyl methyl)-carbazole-4 (3H)-ketone
Make the subhead compound by the described method of embodiment 17E with 37% yield.Mp:155.0-156.0 ℃;
1H NMR (CDCl
3) δ 1.28 (d, J=8.0 Hz, 6H), 3.00 (m, 1H), 4.10 (s, 3H), 5.23 (s, 2H), 6.78 (d, J=9.5 Hz, 2H), 7,11 (m, 2H), 7.28 (m, 3H), 7.37 (t, J=7.9 Hz, 1H), 7.54 (d, J=7.9 Hz, 1H), 7.98 (d, J=7.9 Hz, 1H), 10.46 (s, 1H); ESIMS m/e 374 (M
++ 1); C
24H
23NO
3Ultimate analysis:
Calculated value: C77.19; H6.21; N3.75
Measured value: C76.96; H6.33; The preparation of N3.77D, 5-methoxycarbonyl-4-hydroxyl-2-(1-methylethyl)-9-(phenyl methyl) carbazole
In argon atmospher, (1.15g 5.07mmol) adds embodiment 18C compound (1.90g, 5.07mmol) suspension that forms in dry toluene (30ml) with DDQ to be accompanied by stirring.The mixture that generates was heated 25 minutes under reflux state.After being cooled to room temperature, with mixture chromatogram on silica gel, to toluene/ethyl acetate (97: 3) gradient elution, the required product that obtains is the mixture that has corresponding isopropylidene compound with hexane/toluene (1: 1).In nitrogen atmosphere, this mixture is dissolved in ethyl acetate (30ml), and adds 0.1g PtO
2At room temperature, mixture is depressed stirring 25 minutes at hydrogen balloon.Use diatomite filtration, then recrystallization from ether/hexane obtains the light yellow crystalline solid of subhead compound (0.705g, 37% yield).
Mp:155.0-156.0 ℃;
1H NMR (CDCl
3) δ 1.28 (d, J=8.0 Hz, 6H), 3.00 (m, 1H), 4.10 (s, 3H), 5.23 (s, 2H), 6.78 (d, J=9.5 Hz, 2H), 7.11 (m, 2H), 7.28 (m, 3H), 7.37 (t, J=7.9 Hz, 1H), 7.54 (d, J=8.0 Hz, 1H), 7.98 (d, J=7.9 Hz, 1H), 10.46 (s, 1H); ESIMS m/e 374 (M
++ 1); C
24H
23NO
3Ultimate analysis:
Calculated value: C77.19; H6.21; N3.75
Measured value: C76.96; H6.33; The preparation of N3.77E, 5-formamyl-4-hydroxyl-2-(1-methylethyl)-9-(phenyl methyl) carbazole
Make the subhead compound by the described method of embodiment 17G with 50% yield.Mp 216.0-218.0 ℃;
1H NMR (CDCl
3) δ 1.29 (d, J=6.9,6H), 3.00 (m, 1H), 5.53 (s, 2H), 6.16 (br s, 1H), 6.52 (br s, 1H), 6.78 (d, J=8.6 Hz, 2H), 7.11 (m, 2H), 7.28 (m, 3H), 7.32 (m, 1H), 7.4 (m, 2H), 9.8 (br s, 1H); ESIMS m/e 359.3 (M
++ 1); C
23H
22N
2O
2Ultimate analysis:
Calculated value: C77.07; H6.19; N7.82
Measured value: C77.10; H6.35; The preparation of N7.74F, [5-formamyl-2-(1-methylethyl)-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid methyl esters
Make the subhead compound by the described method of embodiment 17H with 54% yield.Mp 189.0-191.0 ℃;
1H NMR (CDCl
3) δ 1.27 (d, J=6.9 Hz, 6H), 2.98 (m, 1H), 3.84 (s, 3H), 4.90 (s, 2H), 5.51 (s, 2H), 5.8-6.2 (m, 2H), 6.47 (s, 1H), 6.90 (s, 1H), 7.11 (m, 2H), 7.2-7.4 (m, 6H); ESIMS m/e 431 (M
++ 1); C
26H
26N
2O
4Ultimate analysis:
Calculated value: C72.54; H6.09; N6.51
Measured value: C72.58; H6.24; N6.43G, [5-formamyl-2-(1-methylethyl)-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid
Make the subhead compound by the described method of embodiment 17I with 82% yield.
1H?NMR(CDCl
3)δ1.20(d，J＝6.7，6H)，2.94(m，1H)，
4.79(s，2H)，5.63(s，2H)，6.49(s，1H)，7.00-7.40(m，9H)，
7.51(m，1H)，7.70(br?s，1H)，12.94(br?s，1H)；ESIMS?m/e
417 (M
++ 1); C
25H
24N
2O
4Ultimate analysis:
Calculated value: C72.10; H5.81; N6.73
Measured value: C72.11; H5.62; N6.49 embodiment 19[5-formamyl-9-(phenyl methyl)-2-[(three (1-methylethyl) silyl) oxygen ylmethyl] carbazole-4-yl] ethoxyacetic acid
The preparation of A, 3-(2-bromo-3-methoxycarbonyl anilino)-5-(methylol) hexamethylene-2-alkene-1-ketone
According to testing sequence described in the C step synthetic method of embodiment 17, the yield with 68% makes white solid subhead compound.
IR (KBr) 3407 (br), 3364 (br), 3222 (br), 1738,1600,1566cm
-1 1H NMR (DMSO-d
6) δ 1.94 (dd, J=16.5,12.5 Hz, 1H), 2.02-2.15 (m, 2H), 2.32 (dd, J=16.5,9.9 Hz, 1H), 2.50-2.58 (m, 1H), 3.27-3.42 (m, 2H), 3.83 (s, 3H ,-OCH
3), 4.55 (s, 1H ,=CH-), 4.64 (t, J=5.1 Hz, 1H ,-OH), 7.42-7.58 (m, 3H), 8.76 (s, 1H ,-NH); ESIMS m/e 354 (M
++ 1,
79Br), 356 (M
++ 1,
81Br); C
15H
16BrNO
4Ultimate analysis:
Calculated value: C50.87; H4.55; N3.95
Measured value: C51.07; H4.60; N3.93B, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-(methylol)-9H-carbazole-4 (3H)-ketone
According to testing sequence described in the embodiment 17D synthetic method, the yield with 66% makes white solid subhead compound.
IR (KBr) 3350 (br), 1720,1624cm
-1 1H NMR (CDCl
3) δ 1.92-2.20 (m, 2H), 2.33 (dd, J=16.0,3.0 Hz, 1H), 2.44 (dd, J=16.8,9.9 Hz, 1H), 2.67 (dd, J=16.8,4.0 Hz, 1H), 3.33-3.48 (m, 2H), 4.05 (s, 3H ,-OCH
3), 7.20-7.26 (m, 1H), 7.33 (d, J=7.3 Hz, 1H), 7.43 (d, J=7.9 Hz, 1H), 10.25 (s, 1H ,-NH); ESIMS m/e274 (M
++ 1); C
15H
15NO
4Ultimate analysis:
Calculated value: C65.93; H5.53; N5.13
Measured value: C65.68; H5.78; N5.08C, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-(methylol)-9-(phenyl methyl)-carbazole-4 (3H)-ketone
According to testing sequence described in the embodiment 17E synthetic method, the yield with 88% makes white solid subhead compound.
IR (KBr) 3366 (br), 1728,1632cm
-1 1H NMR (CDCl
3) δ 1.98 (s, 1H ,-OH), 2.30-2.62 (m, 3H), 2.72 (dd, J=16.8,9.7 Hz, 1H), 3.06 (dd, J=17.0,3.6 Hz, 1H), 3.58-3.75 (m, 2H), 4.04 (s, 3H ,-OCH
3), 5.25-5.40 (m, 2H ,-NCH
2-), 6.98-7.05 (m, 2H), 7.20-7.40 (m, 6H); ESIMS m/e 364 (M
++ 1) .D, [5-formamyl-9-(phenyl methyl)-2-[(three (1-methylethyl) silyl) oxygen ylmethyl] carbazole-4-yl] preparation of ethoxyacetic acid methyl esters
(the THF solution of 1N, (300mg is in THF 0.522mmol) (5ml) solution 0.626ml) to add embodiment 23D compound with tetrabutylammonium to be accompanied by stirring.Under the room temperature, stirred the mixture 1 hour.After concentrating under 35 ℃ the vacuum condition, resistates is carried out chromatogram purification (with 50-100% tetrahydrofuran (THF)/toluene, using 5% methyl alcohol/tetrahydrofuran (THF) gradient elution more earlier), obtain subhead compound (122mg, 56%) white solid.
IR (KBr) 3380 (br), 3205 (br), 1733,1641,1628cm
-1 1H NMR (DMSO-d
6) δ 3.69 (s, 3H ,-OCH
3), 4.55 (s, 2H ,-OCH
2-), 4.86 (s, 2H ,-OCH
2-), 5.22 (br s, 1H ,-OH), 5.62 (s, 2H ,-NCH
2-), 6.53 (s, 1H), 7.00-7.25 (m, 8H), 7.32 (br t, J=7.7 Hz, 1H), 7.50 (br d, J=7.7 Hz, 1H), 7.53 (br d, J=7.7 Hz, 1H); ESIMSm/e 419 (M
++ 1); C
24H
22N
2O
5Ultimate analysis:
Calculated value: C68.89; H5.30; N6.69
Measured value: C68.80; H5.17; N6.72E, [5-formamyl-9-(phenyl methyl)-2-[(three (1-methylethyl) silyl) oxygen ylmethyl] carbazole-4-yl] preparation of ethoxyacetic acid
According to testing sequence described in the embodiment 17I synthetic method, the yield with 99% makes white solid subhead compound.
IR (KBr) 3427,3331 (br), 1732,1682,1636cm
-1 1H NMR (DMSO-d
6) δ 4.55 (d, J=4.6 Hz, 2H ,-OCH
2OH), 4.78 (s, 2H ,-OCH
2-), 5.25 (br t, J=4.6 Hz, 1H ,-OH), 5.62 (s, 2H ,-NCH
2-), 6.57 (s, 1H), 7.00-7.25 (m, 7H), 7.33 (br t, J=7.8 Hz, 1H), 7.39 (s, 1H ,-NH), 7.55 (d, J=7.8 Hz, 1H), 7.72 (s, 1H ,-NH), 12.93 (s, 1H ,-CO
2H); ESIMS m/e 405 (M
++ 1); C
23H
20N
2O
50.3H
2The O ultimate analysis:
Calculated value: C67.41; H5.07; N6.84
Measured value: C67.34; H5.13; N6.98 embodiment 20[5-formamyl-2-phenyl-9-(phenyl methyl) carbazole-4-yl] preparation of ethoxyacetic acid
The preparation of A, 3-(2-bromo-3-methoxycarbonyl anilino)-5-phenyl hexamethylene-2-alkene-1-ketone
The described method of A step by embodiment 17 makes the subhead compound with 61% yield.
IR (KBr) 3180 (br), 1734,1592cm
-1 1H NMR (CDCl
3) δ 2.64-2.71 (m, 2H), 2.84 (dd, J=11.7,16.2 Hz, 1H), 3.45-3.49 (m, 1H), 3.95 (s, 3H) 5.67 (s, 1H), 6.29 (br s, 1H), 7.29-7.40 (m, 6H), 7.54-7.59 (m, 2H); ESIMS m/e 400 (M
++ 1,
79Br), 402 (M
++ 1,
81Br); C
20H
18BrNO
3Ultimate analysis:
Calculated value: C60.01; H4.53; N3.50
Measured value: C60.23; H4.80; N3.47B, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-phenyl-9H-carbazole-4 (3H)-ketone
Make the subhead compound by the described method of embodiment 17D with 70% yield.
IR (KBr) 3180,1736,1628cm
-1 1H NMR (CDCl
3) δ 2.70 (d, J=4Hz, 1H), 2.72 (s, 1H), 2.97-3.03 (m, 2H), 4.03 (s, 3H), 7.18-7.39 (m, 8H), 9.52 (br s, 1H); ESIMS m/e 320 (M
++ 1) .C, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-phenyl-9-(phenyl methyl)-carbazole-4 (3H)-ketone
Make the subhead compound by the described method of embodiment 17E with 85% yield.IR(KBr)1723，1652cm
-1；ESIMS?m/e?410(M
++1)。The preparation of D, 5-methoxycarbonyl-4-hydroxyl-2-phenyl-9-(phenyl methyl) carbazole
Make the subhead compound by the described method of embodiment 17F (a) with 50% yield.IR (KBr) 3326,1711cm
-1 1H NMR (CDCl
3) δ 4.10 (s, 3H), 5.52 (s, 2H), 7.08-7.10 (m, 4H), 7.24-7.56 (m, 7H), 7.38 (d, J=8.1 Hz, 1H), 7.55 (d, J=8.0 Hz, 2H), 7.97 (d, J=8.1 Hz, 1H) 10.43 (br s, 1H); ESIMS m/e 408 (M
++ 1); C
27H
21NO
30.1C
7H
8Ultimate analysis:
Calculated value: C79.85; H5.27; N3.36
Measured value: C80.19; H5.32; The preparation of N3.49E, 5-formamyl-4-hydroxyl-2-phenyl-9-(phenyl methyl) carbazole
Make the subhead compound by the described method of embodiment 17G with 40% yield.
1H NMR (CDCl
3) δ 5.58 (s, 2H), 6.25 (s, 1H), 6.59 (s, 1H), 7.11-7.16 (m, 4H), 7.26-7.48 (m, 8H), 7.52 (d, J=8.1 Hz, 1H), 7.68 (d, J=7.2 Hz, 2H), 9.99 (br s, 1H); ESIMS m/e 393 (M
++ 1) preparation of .F, [5-formamyl-2-phenyl-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid methyl esters
Make the subhead compound by the described method of embodiment 17H with 58% yield.IR (KBr) 3359,1755,1634cm
-1 1H NMR (CDCl
3) δ 3.85 (s, 3H), 4.96 (s, 2H), 5.58 (s, 2H), 5.92 (br s, 2H), 7.11 (s, 1H), 7.13-7.24 (m, 2H), 7.26-7.30 (m, 3H), 7.34-7.47 (m, 7H), 7.59 (d, J=7.3 Hz, 2H); ESIMS m/e 465 (M
++ 1); C
29H
24N
2O
4Ultimate analysis:
Calculated value: C74.98; H5.21; N6.03
Measured value: C74.97; H5.22; N5.80G, [5-formamyl-2-phenyl-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid
Make the subhead compound by the described method of embodiment 17I with 86% yield.
IR (KBr) 3426,3332,2625-2100 (br), 1734,1636cm
-1 1H NMR (DMSO-d
6) δ 4.94 (s, 2H), 5.57 (s, 2H), 6.96 (s, 1H), 7.06-7.31 (m, 6H), 7.33-7.47 (m, 5H), 7.55-7.60 (m, 2H), 7.71-7.73 (m, 3H), 12.94 (br s, 1H); ESIMS m/e 451 (M
++ 1); C
28H
22N
2O
4Ultimate analysis:
Calculated value: C74.65; H4.92; N6.22
Measured value: C74.87; H5.15; N6.11 embodiment 21[5-formamyl-2-(4-chloro-phenyl-)-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid
The preparation of A, 3-(2-bromo-3-methoxycarbonyl anilino)-5-(4-chloro-phenyl-) hexamethylene-2-alkene-1-ketone
The described method of C step by embodiment 17 makes the subhead compound with 80% yield.
1H NMR (CDCl
3) δ 2.66 (m, 3H), 2.86 (m, 1H), 3.44 (m, 1H), 3.95 (s, 3H), 5.75 (s, 1H), 7.24 (m, 3H), 7.32 (m, 3H), 7.57 (t, J=7.1 Hz, 2H); ESIMS m/e 434 (M
++ 1,
79Br
35Cl), 436 (M
++ 1,
81Br
35Cl,
79Br
37Cl), 438 (M
++ 1,
81Br
37Cl); C
20H
17BrClNO
3Ultimate analysis:
Calculated value: C55.26; H3.94; N3.22
Measured value: C55.55; H3.91; N3.21B, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-(4-chloro-phenyl-)-9H-carbazole-4 (3H)-ketone
Make the subhead compound by the described method of embodiment 17D with 64% yield.
1H NMR (CDCl
3) δ 2.72 (m, 2H), 2.99 (dd, J=16.7,16.5 Hz, 1H), 3.12 (dd, J=16.7,4.7 Hz, 1H), 3.45 (m, 1H), 4.04 (s, 3H), 7.17 (d, J=8.5 Hz, 2H), 7.23 (d, J=7.9 Hz, 1H), 7.30 (d, J=8.4 Hz, 2H), 7.43 (t, J=7.9 Hz, 2H), 9.61 (br s, 1H); ESIMS m/e 354 (M
++ 1,
35Cl), 356 (M
++ 1,
37Cl); C
20H
16ClNO
3Ultimate analysis:
Calculated value: C67.90; H4.56; N3.96
Measured value: C68.14; H4.51; N3.90C, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-(4-chloro-phenyl-)-9-(phenyl methyl)-carbazole-4 (3H)-ketone
Make the subhead compound by the described method of embodiment 17E with 90% yield.
1H NMR (CDCl
3) δ 2.79 (d, J=3.7 Hz, 1H), 2.82 (s, 1H), 2.97 (dd, J=16.7,11.5 Hz, 1H), 3.19 (dd, J=16.7,4.7 Hz, 1H), 3.59 (m, 1H), 4.06 (s, 3H), 5.35 (s, 2H), 6.96 (t, J=3.6Hz, 2H), 7.21 (m, 2H), 7.30 (m, 6H), 7.36 (t, J=7.5Hz, 2H); ESIMS m/e 444 (M
++ 1,
35Cl), 446 (M
++ 1,
37Cl); C
27H
22ClNO
3Ultimate analysis:
Calculated value; C73.05; H5.00; N3.16
Measured value: C73.23; H5.15; The preparation of N3.36D, 5-methoxycarbonyl-2-(4-chloro-phenyl-)-4-hydroxyl-9-(phenyl methyl) carbazole
Make the subhead compound by the described method of embodiment 17 (b) with 66% yield.
1H NMR (CDCl
3) δ 4.12 (s, 3H), 5.60 (s; 2H), 7.10 (t, J=4.5 Hz; 4H), 7.32 (m, 3H); 7.41 (m, 3H), 7.60 (d; J=8.5 Hz, 3H), 8.04 (d; J=7.2 Hz, 1H) preparation of .E, 5-formamyl-2-(4-chloro-phenyl-)-4-hydroxyl-9-(phenyl methyl) carbazole
Make the subhead compound by the described method of embodiment 17G with 43% yield.
1H NMR (CDCl
3) δ 5.77 (s, 2H), 6.89 (s, 1H), 7.07 (d, J=7.0 Hz, 2H), 7.23 (m, 3H), 7.45 (m, 5H), 7.76 (d, J=8.4 Hz, 3H), 8.40 (s, 1H), 8.85 (s, 1H); ESIMS m/e 427 (M
++ 1,
35Cl), 42 9 (M
++ 1,
37Cl); C
26H
19ClN
2O
2Ultimate analysis:
Calculated value: C73.15; H4.49; N6.56
Measured value: C72.92; H4.57; The preparation of N6.46F, [5-formamyl-2-(4-chloro-phenyl-)-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid methyl esters
Make the subhead compound by the described method of embodiment 17H with 79% yield.
1H NMR (CDCl
3) δ 3.84 (s, 3H), 4.97 (s, 2H), 5.57 (s, 2H), 6.08 (br s, 1H), 6.14 (br s, 1H), 6.74 (s, 1H), 7.12 (m, 2H), 7.18 (s, 1H), 7.22 (m, 2H), 7.41 (m, 6H), 7.51 (d, J=8.5Hz, 2H); ESIMS m/e 499 (M
++ 1,
35Cl), 501 (M
++ 1,
37Cl) .G, [5-formamyl-2-(4-chloro-phenyl-)-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid
Make the subhead compound by the described method of embodiment 17I with 100% yield.
1H NMR (CDCl
3) δ 4.95 (s, 2H), 5.75 (s, 2H), 6.88 (s, 1H), 7.20 (m, 4H), 7.52 (m, 6H), 7.76 (m, 3H), 12.92 (s, 1H); ESIMS m/e 485 (M
++ 1,
35Cl), 487 (M
++ 1,
37Cl). embodiment 22[5-formamyl-2-(2-furyl)-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid
The preparation of A, 3-(2-bromo-3-methoxycarbonyl anilino)-5-(2-furyl) hexamethylene-2-alkene-1-ketone
The described method of C step by embodiment 17 makes the subhead compound with 55% yield.
IR (KBr) 3201,1735,1593,1575cm
-1 1H NMR (CDCl
3) δ 2.56-2.94 (m, 4H), 3.53-3.60 (m, 1H), 3.94 (s, 1H), 5.60 (s, 1H), 6.11 (d, J=2.8Hz, 1H), 6.22 (br s, 1H), 6.32-6.34 (m, 1H), 7.34-7.39 (m, 1H), 7.37 (br s, 1H), 7.55 (d, J=7.9Hz, 2H); M/e 390 (M
++ 1,
79Br), 392 (M
++ 1,
81Br); C
18H
16BrNO
4Ultimate analysis:
Calculated value: C55.40; H4.13; N3.59
Measured value: C55.62; H4.27; N3.71B, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-(2-furyl)-9H-carbazole-4 (3H)-ketone
Make the subhead compound by the described method of embodiment 17D with 47% yield.IR (KBr) 1736,1633cm
-1 1H NMR (THF-d
8): δ 2.59-2.77 (m, 2H), 3.14 (dd, J=16.5,10.5 Hz, 1H), 3.30 (dd, J=16.5,10.3 Hz, 1H), 3.56-3.69 (m, 1H), 3.81 (s, 3H), 6.13-6.14 (m, 1H), and 6.27-6.29 (d, J=2.5 Hz, 1H), 7.11-7.21 (m, 2H), 7.37-7.39 (m, 1H), 7.39 (s, 1H), 11.03 (br s, 1H); ESIMS m/e 310 (M
++ 1); C
18H
15NO
40.1C
7H
8Ultimate analysis:
Calculated value: C70.51; H4.50; N4.40
Measured value: C70.75; H4.85; N4.61C, 5-methoxycarbonyl-1, the preparation of 2-dihydro-2-(2-furyl)-9-(phenyl methyl)-carbazole-4 (3H)-ketone
Make the subhead compound by the described method of embodiment 17E with 91% yield.(KBr) 3500 (br), 1722,1650cm
-1 1H NMR (CDCl
3) δ 2.79 (dd, J=16.6,10.8 Hz, 1H), 2.94 (dd, J=16.6,4.2 Hz, 1H), 3.06 (dd, J=16.8,9.8 Hz, 1H), 3.31 (dd, J=18.8,4.7 Hz, 1H), 3.68-3.74 (m, 1H), 4.06 (s, 3H), 5.37 (s, 2H), 6.08 (d, J=2.7 Hz, 1H), 6.28 (m, 1H), 6.96 (m, 2H), 7.22-7.40 (m, 7H); ESIMS m/e 400 (M
++ 1); C
25H
21NO
4Ultimate analysis:
Calculated value: C75.17; H5.30; N3.51
Measured value: C75.46; H5.32; The preparation of N3.67D, 5-methoxycarbonyl-2-(2-furyl)-4-hydroxyl-9-(phenyl methyl) carbazole
Make the subhead compound by the described method of embodiment 17F (b) with 72% yield.IR (KBr) 3500 (br), 1674cm
-1 1H NMR (CDCl
3) δ 4.11 (s, 3H), 5.58 (s, 2H), 6.48-6.50 (m, 1H), 6.75 (d, J=3.2 Hz, 1H), 7.09-7.12 (m, 2H), 7.16 (s, 1H), 7.26-7.30 (m, 4H), 7.36-7.44 (t, J=8.0 Hz, 1H), 7.48 (s, 1H), 7.56 (d, J=8.1 Hz, 1H), 8.01 (d, J=7.5 Hz, 1H), 10.50 (br s, 1H); ESIMS m/e 398 (M
++ 1) preparation of .E, 5-formamyl-2-(2-furyl)-4-hydroxyl-9-(phenyl methyl) carbazole
Make the subhead compound by the described method of embodiment 17G with 60% yield.
IR (KBr) 3425 (br), 3325 (br), 1642,1628cm
-1 1H NMR (DMSO-d
6) δ 5.72 (s, 2H), 6.56-6.57 (m, 1H), 6.95 (s, 1H), 6.98 (d, J=3.0 Hz, 1H), 7.07 (d, J=7.2 Hz, 2H), 7.17-7.26 (m, 3H), 7.42-7.43 (m, 3H), 7.71-7.76 (m, 2H), 8.38 (s, 1H), 8.83 (s, 1H), 10.70 (s, 1H); ESIMS m/e 381 (M
--1); C
24H
18N
2O
3Ultimate analysis:
Calculated value: C75.38; H4.74; N7.33
Measured value: C75.35; H4.95; The preparation of N7.29F, [5-formamyl-2-(2-furyl)-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid methyl esters
Make the subhead compound by the described method of embodiment 17H with 80% yield.IR (KBr) 3358,1756,1643cm
-1 1H NMR (DMSO-d
6) δ 3.70 (s, 3H), 4.98 (s, 2H), 5.70 (s, 2H), 6.58 (d, J=1.5 Hz, 1H), 6.93 (s, 1H), 7.01-7.30 (m, 8H), 7.35 (t, J=7.7 Hz, 1H), 7.51-7.57 (m, 3H), 7.72 (s, 1H); ESIMS m/e 455 (M
++ 1); C
27H
22N
2O
5Ultimate analysis:
Calculated value: C71.36; H4.88; N6.16
Measured value: C71.46; H4.91; N6.24G, [5-formamyl-2-(2-furyl)-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid
Make the subhead compound by the described method of embodiment 17I with 88% yield.
1HNMR (DMSO-d
6) δ 4.89 (s, 2H) 5.71 (s, 2H), 6.58 (s, 1H), 6.94 (s, 1H), 7.00-7.38 (m, 9H), 7.59 (d, J=9.2 Hz, 1H), 7.58 (s, 1H), 7.72 (br s, 2H), 12.98 (br s, 1H); ESIMS m/e441 (M
++ 1); C
26H
20N
2O
5Ultimate analysis:
Calculated value: C70.90; H4.58:N6.36
Measured value: C71.20; H4.67; N6.28 embodiment 23[5-formamyl-9-(phenyl methyl)-2-[(three (1-methylethyl) silyl) oxygen ylmethyl] carbazole-4-yl] the ethoxyacetic acid lithium salts
A, 5-methoxycarbonyl-1,2-dihydro-9-(phenyl methyl)-2-[(three (1-methylethyl) silyl) oxygen ylmethyl] preparation of carbazole-4 (3H)-ketone
Under 0 ℃, in nitrogen atmosphere, be accompanied by stirring with trifluoromethanesulfonic acid triisopropyl silyl ester (2.46ml.9.15mmol) add embodiment 19C compound (2.89g, 7.95mmol) and anhydrous pyridine (0.964ml is 11.9mmol) in anhydrous methylene chloride (29ml) in the suspension of formation.Stirred the mixture 1 hour at 0 ℃, (0.5ml) adds this mixture with methyl alcohol, and continues to stir 1 minute.With after toluene (10ml) dilution, enriched mixture, and with resistates in the enterprising circumstances in which people get things ready for a trip spectrum of silica gel purifying (with 10-50% ethyl acetate/hexane gradient elution), obtain subhead compound (4.06g, 98%) white solid.IR (KBr) 1725,1645cm
-1 1H NMR (CDCl
3) δ 0.90-1.15 (m, 21H ,-CH (CH
3)
2), 2.50-2.63 (m, 3H), 2.74-2.86 (m, 1H), 3.02 (br d, J=7.7 Hz, 1H), 3.67-3.81 (m, 2H ,-CH
2O-), 4.05 (s, 3H ,-OCH
3), 5.37 (s, 2H ,-NCH
2-), 7.00-7.04 (m, 2H), 7.22-7.44 (m, 6H); ESIMS m/e 520 (M
++ 1); C
31H
41NO
4The Si ultimate analysis:
Calculated value: C71.64; H7.95; N2.69
Measured value: C71.75; H7.91; N2.82B, 5-methoxycarbonyl-4-hydroxyl-9-(phenyl methyl)-2-[(three (1-methylethyl) silyl) oxygen ylmethyl] preparation of carbazole
According to testing sequence (b) described in the embodiment 17F synthetic method, the yield with 93% makes light yellow solid shape subhead compound.IR (KBr) 3165 (br), 1671,1629cm
-1 1H NMR (CDCl
3) δ 1.00-1.22 (m, 21H ,-CH (CH
3)
2), 4.10 (s, 3H ,-OCH
3), 4.97 (s, 2H ,-OCH
2-), 5.51 (s, 2H ,-NCH
2-), 6.79 (s, 1H), 7.05-7.14 (m, 3H), 7.20-7.30 (m, 3H), 7.39 (t, J=8.0 Hz, 1H), 7.59 (d, J=8.0 Hz, 1H), 7.98 (d, J=8.0 Hz, 1H), 10.50 (s, 1H ,-OH); ESIMS m/e 518 (M
++ 1); C
31H
39NO
4The Si ultimate analysis:
Calculated value: C71.92; H7.59; N2.71
Measured value: C72.19; H7.21; N2.76C, 5-formamyl-4-hydroxyl-9-(phenyl methyl)-2-[(three (1-methylethyl) silyl) oxygen ylmethyl] preparation of carbazole
According to testing sequence described in embodiment 17F (b) synthetic method, the yield with 80% makes light yellow solid shape subhead compound.
IR (KBr) 3348 (br), 3200,1660,1628cm
-1 1H NMR (CDCl
3) δ 1.00-1.20 (m, 21H ,-CH (CH
3)
2), 4.94 (s, 2H ,-OCH
2-), 5.52 (s, 2H ,-NCH
2-), 6.22 (s, 1H ,-NH), 6.56 (s, 1H ,-NH), 6.75 (s, 1H), 7.05-7.10 (m, 3H), 7.20-7.28 (m, 3H), 7.36 (t, J=7.6 Hz, 1H), 7.43 (d, J=7.6 Hz, 1H), 7.53 (d, J=7.6 Hz, 1H), 9.75 (brs, 1H ,-OH); ESIMS m/e 503 (M
++ 1) .D, [5-formamyl-9-(phenyl methyl)-2-[(three (1-methylethyl) silyl) oxygen ylmethyl] carbazole-4-yl] preparation of ethoxyacetic acid methyl esters
According to testing sequence described in the embodiment 17H synthetic method, the yield with 94% makes white solid subhead product.
IR (KBr) 3484,3180 (br), 1764,1675cm
-1 1H NMR (CDCl
3) δ 1.00-1.20 (m, 21H ,-CH (CH
3)
2), 3.82 (s, 3H ,-OCH
3), 4.89 (s, 2H ,-OCH
2-), 4.93 (s, 2H ,-OCH
2-), 5.50 (s, 2H ,-NCH
2-), 6.00 (br s, 2H ,-NH
2), 6.60 (s, 1H), 7.05-7.12 (m, 3H), 7.22-7.28 (m, 3H), 7.32-7.38 (m, 1H), 7.39-7.41 (m, 2H); ESIMS m/e 575 (M
++ 1); C
33H
42N
2O
5The Si ultimate analysis:
Calculated value: C68.96; H7.37; N4.87
Measured value: C69.14; H7.20; N4.95E, [5-formamyl-9-(phenyl methyl)-2-[(three (1-methylethyl) silyl) oxygen ylmethyl] carbazole-4-yl] preparation of ethoxyacetic acid lithium salts
Be accompanied by stirring, ((50.9mg is 0.0886mmol) at THF (1ml)/CH 0.177mmol) to add above-mentioned D stepwise compound for 4.17N, 42.5ml with lithium hydroxide
3OH (0.3ml)/H
2The suspension that forms among the O (0.3ml).Under 55 ℃, the mixture that generates is stirred 1 hour formation white suspension in oil bath.Under the room temperature, water (5ml) dilutes above-mentioned white suspension, and makes the THF evaporation under vacuum condition.After filtering and washing with water,, obtain title product (40.0mg, 80%) with white solid vacuum-drying.
IR (KBr) 3470,3315,1652,1621cm
-1 1H NMR (DMSO-d
6) δ 0.90-1.15 (m, 21H ,-CH (CH
3)
2), 4.29 (s, 2H ,-OCH
2-), 4.84 (s, 2H ,-OCH
2-), 5.57 (s, 2H ,-NCH
2-), 6.49 (s, 1H), 7.00-7.25 (m, 7H), 7.31 (brt, J=7.9 Hz, 1H), 7.43 (br s, 1H ,-NH), 7.59 (br d, J=7.9 Hz, 1H), 7.72 (br s, 1H ,-NH); ESIMS m/e 567 (M
++ 1). preparation example 3 prepares 5-methoxycarbonyl-1 by 2-chloro-3-nitrobenzoic acid, 2-dihydro-9H-carbazole-4 (3H)-ketone
A) 2-chloro-3-nitrobenzoic acid methyl esters
At room temperature, with 2-chloro-3-nitrobenzoic acid (20.16g, 100.0mM), methyl iodide (15.6g, 110mM) and salt of wormwood (15.0g, the solution stirring that 108.5mM) in 100ml DMF, forms 48 hours; Again mixture is poured in 1.5 premium on currency.The precipitation that generates is collected, obtain 20.0g (93%) 2-chloro-3-nitrobenzoic acid methyl esters white solid.
1H NMR (CDCl
3) δ 8.42 (dd, 1H, J=1 and 8 Hz), 8.18 (dd, 1H, J=1 and 8 Hz), 7.43 (t, 1H, J=8 Hz), and 3.9 (s, 3H) .IR (KBr, cm
-1) 1743,1719,1595,1540,1532,1433,1357,1300, and 730.MS (FD) m/e 215,216.C
8H
6NO
4The Cl ultimate analysis:
Calculated value: C44.57; H3.81; N6.50
Measured value: C44.19; H3.45; N6.19b) 2-chloro-3-Methyl anthranilate
Under the room temperature, with hydrogen feed by 2-chloro-3-nitrobenzoic acid methyl esters (10.0g, 46.4mM) and the solution that in the 150ml ethyl acetate, forms of 1.0g 3% sulfurized platinum/carbon 48 hours.Remove catalyzer by diatomite filtration, concentrated filtrate obtains 8.6g (100%) 2-chloro-3-Methyl anthranilate yellow oil.
1H NMR (CDCl
3) δ 7.25 (dd, 1H, J=1 and 8 Hz), 7.2 (t, 1H, J=8 Hz), 6.95 (dd, 1H, J=1 and 8 Hz), and 3.9 (s, 3H) .IR (CHCl
3, cm
-1) 3450,3380,2980,2900,1729,1615,1456,1434,1322,1290, and 1268.MS (ES) m/e 186,188.C
8H
8NO
2The Cl ultimate analysis:
Calculated value: C51.77; H4.34; N7.55
Measured value: C51.52; H4.17; N7.54b) 2-chloro-3-Methyl anthranilate
Under 15-20 ℃, (27.0g, 137.0mM) solution in the 55ml concentrated hydrochloric acid slowly added 2-chloro-3-nitrobenzoic acid methyl esters (6.0g is 27.9mM) in the solution in 75ml ethanol in 1 hour with tin protochloride.Then, under 50-60 ℃, heated mixt 15 minutes.This mixture is cooled to room temperature, and remains in temperature under 30-35 ℃ the situation and make it become alkalescence by slow adding solid sodium hydroxide.The mixture that generates with chloroform extraction three times, and, use dried over sodium sulfate with extracting solution salt water washing, filter and concentrate, obtain 2.6g (50%) 2-chloro-3-Methyl anthranilate yellow oil, and this product is all the same with the material that obtains by above-mentioned catalytic hydrogenation in every respect.B) 2-chloro-3-Methyl anthranilate
Under 25 ℃, with V-Brite B (14.0g, 20.0mM) and the solution of yellow soda ash (6.7g) in 200ml water in 30 minutes, slowly add 2-chloro-3-nitrobenzoic acid methyl esters (6.0g, 27.9mM) solution in 40ml methyl alcohol and 40ml tetrahydrofuran (THF).With mixture restir 30 minutes at room temperature, use ethyl acetate extraction then, and with extracting solution salt water washing, use dried over sodium sulfate, filter and concentrate, obtain 1.2g (33%) 2-chloro-3-Methyl anthranilate yellow oil, and this product is all the same with the material that obtains by above-mentioned catalytic hydrogenation in every respect.C) 3-(3-methoxycarbonyl-2-chloroanilino)-hexamethylene-2-alkene-1-ketone
Under 120 ℃, in nitrogen atmosphere, the heating by 2-chloro-3-Methyl anthranilate (11.11g, 59.86mM) and hydroresorcinol (9.05g, 80.8mM) mixture of Zu Chenging is 4 hours.The solid that generates is developed with hot ethyl acetate, dry under vacuum condition then, obtain 14.05g (84%) 3-(3-methoxycarbonyl-2-chloroanilino)-hexamethylene-2-alkene-1-ketone orange/yellow solid.
1H NMR (CDCl
3) δ 7.6 (dt, 1H, J=1 and 8 Hz), 7.3 (t, 1H, J=8 Hz), 6.6 (br s, 1H), 5.62 (s, 1H), 3.95 (s, 3H), 2.6 (t, 2H, J=6 Hz), 2.4 (t, 2H, J=6 Hz), and 2.1 (m, 2H) .IR (CHCl
3, cm
-1) 3050,2950,1729,1536,1351,1299,1290,1267, and 1135.MS (ES) m/e 278,280,282.C
14H
14NO
3The Cl ultimate analysis:
Calculated value: C60.11; H5.04; N5.01
Measured value: C57.51; H4.99; N4.68d) 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone
Under 130 ℃, will be by 3-(3-methoxycarbonyl-2-chloroanilino)-hexamethylene-2-alkene-1-ketone (10.22g, 36.67mM), ether palladium (0.82g, 3.66mM), tricyclohexyl phosphine (4.10g, 14.62mM) and triethylamine (30.0ml, 21.78g 215.2mM) suspension that forms in the 100ml acetonitrile heated in sealed vessel 14 days.Mixture is diluted with ethyl acetate,, wash secondary with water, with the saturated brine washing once, use anhydrous magnesium sulfate drying, filter, and concentrate, obtain 9.9g light brown jelly with 1N HCl washing secondary.On silica gel,, obtain 4.68g (52%) 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone yellow solid by HPLC purifying (using the dichloromethane/ethyl acetate gradient elution).
1H NMR (CDCl
3) δ 9.15 (br s, 1H), 7.4 (dd, 1H, J=1 and 8 Hz), 7.35 (dd, 1H, J=1 and 8Hz), 7.25 (t, 1H, J=8 Hz), 4.05 (s, 3H), 2.95 (t, 2H, J=6Hz), 2.55 (t, 2H, J=6 Hz), and 2.2 (m, 2H) .IR (CHCl
3, cm
-1) 3400,3200 (br), 3000,2950,1721,1646,1466,1439,1427,1299,1284,1165, and 1135.MS (ES) m/e 242,244.C
14H
13NO
3Ultimate analysis:
Calculated value: C69.12; H5.39; N5.76
Measured value: C68.82; H5.67; N5.60 preparation example 4 prepares 5-methoxycarbonyl-1 by 2-bromo-3-nitrobenzoic acid, 2-dihydro-9H-carbazole-4 (3H)-ketone
A) 2-bromo-3-nitrobenzoic acid methyl esters
At room temperature, with 2-bromo-3-nitrobenzoic acid (28.4g, 115.0mM), methyl iodide (18.0g, 127mM) and salt of wormwood (19.0g, the solution stirring that 137.4mM) in 100ml DMF, forms 72 hours; Again mixture is poured in 1.5 premium on currency.Collect by filtering the precipitation that will generate, and dry under vacuum condition, obtain 28.79g (96%) 2-bromo-3-nitrobenzoic acid methyl esters white solid.
1H NMRDMSO-d6) δ 8.3 (dd, 1H, J=1 and 8 Hz), 7.9 (dd, 1H, J=1 and8 Hz), 7.7 (t, 1H, J=8 Hz), and 3.9 (s, 3H) .IR (KBr, cm
-1) 2950,1738,1541,1435,1364,1298, and 1142.MS (FD) m/e259,261.C
8H
6NO
4The Br ultimate analysis:
Calculated value: C36.95; H2.33; N5.39
Measured value: C37.14; H2.37; N5.45b) 2-bromo-3-Methyl anthranilate
Under the room temperature, with hydrogen feed by 2-bromo-3-nitrobenzoic acid methyl esters (0.20g, 0.77mM) and the solution that in the 25ml ethyl acetate, forms of 1.0g 3% sulfurized platinum/carbon 24 hours.Remove catalyzer by diatomite filtration, concentrated filtrate obtains 0.175g (99%) 2-bromo-3-Methyl anthranilate yellow oil.
1H NMR (CDCl
3) δ 7.15 (t, 1H, J=8 Hz), 7.1 (dd, 1H, J=1 and 8 Hz), 6.8 (dd, 1H, J=1 and 8 Hz), and 3.95 (s, 3H) .IR (CHCl
3, cm
-1) 3550,3380,2980,2900,1729,1613,1465,1451,1434,1324,12 66, and 1025.MS (FD) m/e 230,232.C
8H
8NO
2The Br ultimate analysis:
Calculated value: C41.77; H3.51; N6.09
Measured value: C42.01; H3.29; N6.00b) 2-bromo-3-Methyl anthranilate
Under 15-30 ℃, (15.0g, 76.1mM) solution in the 30ml concentrated hydrochloric acid slowly added 2-bromo-3-nitrobenzoic acid methyl esters (4.0g, 15.4mM) solution in 90ml ethanol in 1 hour with tin protobromide.Then, under 50-60 ℃, heated mixt 15 minutes.This mixture is cooled to room temperature, and remains in temperature under 30-35 ℃ the situation and make it become alkalescence by slow adding solid sodium hydroxide.The mixture that generates with chloroform extraction three times, and, use dried over sodium sulfate with extracting solution salt water washing, filter and concentrate, obtain 3.51g (99%) 2-bromo-3-Methyl anthranilate yellow oil, and this product is all the same with the material that obtains by above-mentioned catalytic hydrogenation in every respect.C) 3-(3-methoxycarbonyl-2-bromobenzene amido)-hexamethylene-2-alkene-1-ketone
Under 125 ℃, in nitrogen atmosphere, the heating by 2-bromo-3-Methyl anthranilate (13.2g, 60.0mM) and hydroresorcinol (8.4g, 75mM) mixture of Zu Chenging is 4 hours.The solid that generates is passed through HPLC purifying (using the dichloromethane/ethyl acetate wash-out) on silica gel, obtain 17.2g (88%) 3-(3-methoxycarbonyl-2-bromobenzene amido)-hexamethylene-2-alkene-1-ketone tawny foam.
1H NMR (DMSO-d6) δ 8.75 (s, 1H), 7.6-7.4 (m, 3H), 4.65 (s, 1H), 3.85 (s, 3H), 2.6 (t, 2H, J=6 Hz), 2.15 (t, 2H, J=6 Hz), and 1.9 (m, 2H) .IR (CHCl
3, cm
-1) 3400,3004,2954,1732,1607,1588,1573,1513,1464,1436,1412,1308,1249,1177, and 1144.MS (ES) m/e 322,324,326.C
14H
14NO
3The Br ultimate analysis:
Calculated value: C51.85; H4.32; N4.32
Measured value: C53.60; H4.73; N4.09d) 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone
Will be by 3-(3-methoxycarbonyl-2-bromobenzene amido)-hexamethylene-2-alkene-1-ketone (15.8g, 48.8mM), acid chloride (1.12g, 5.0mM), three-neighbour-tolylphosphine (3.1g, 10.0mM) and triethylamine (6.3g, 62.0mM) suspension that forms in the 120ml acetonitrile heated 8 hours under the backflow situation.Under vacuum condition,, resistates is dissolved in methylene dichloride,, washes secondary with water, with the saturated brine washing once, use anhydrous magnesium sulfate drying, filter with 1N HCl washing secondary except that after desolvating, and concentrated, obtain 17g light brown foam.On silica gel, pass through HPLC purifying (using the dichloromethane/ethyl acetate gradient elution), obtain 9.2g (78%) 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone yellow solid, and this product is with above-mentioned the same from material that 3-(3-methoxycarbonyl-2-chloroanilino)-hexamethylene-2-alkene-1-ketone obtains.
1H NMR (DMSO-d6) δ 7.5 (d, 1H, J=8 Hz); 7.25-7.1 (m, 2H), 5.7 (s; 1H), 3.8 (s, 3H); (2.95 t, 2H, J=6 Hz); (2.4 t, 2H ,=6 Hz); and 2.1 (m, 2H) .MS (ES) m/e 242,244. embodiment 24{9-[(phenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 9-[(phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (300mg, 1.23mM), bromotoluene (210mg, 1.23mM) and salt of wormwood (170mg, the suspension that 1.23mM) forms in 15ml DMF stirred 6 hours.With mixture 80ml water dilution and freezing at refrigerator, the white precipitate that generates is collected by filtering, washed with water, and dry under vacuum condition, obtain 325mg (79%) 9-[(phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone white solid.
1H NMR (DMSO-d6) δ 7.7 (dd, 1H, J=1 and 8 Hz), 7.45-7.0 (m, 7H), 5.6 (s, 2H), 3.8 (s, 3H), 3.05 (t, 2H, J=6 Hz), 2.5 (t, 2H, J=6 Hz), and 2.2 (m, 2H) .IR (KBr, cm
-1) 3421,1726,1676,1636,1473,1450,1435,1288,1122,764,745, and 706.MS (ES) m/e 334.C
21H
19NO
3Ultimate analysis:
Calculated value: C75.68; H5.71; N4.20
Measured value: C70.85; H5.53; N4.49B, 9-[(phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole (a) is the 9-[(phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone (1.5g, 4.5mM) and 2,3-two chloro-5,6-dicyano-1, (1.12g, 5.0mM) solution that forms in 25ml toluene stirred 6 hours between 80-90 ℃ the 4-benzoquinones.Mixture is directly passed through column chromatography purifying (using the dichloromethane/ethyl acetate wash-out) on silica gel, obtains 420mg (28%) 9-[(phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1H NMR (DMSO-d6) δ 10.25 (s, 1H), 7.7 (d, 1H, J=8 Hz), 7.4 (t, 1H, J=8 Hz), 7.4-7.0 (m, 8H), 6.6 (d, 1H, J=8 Hz), 5.6 (s, 2H), and 3.8 (s, 3H) .IR (CHCl
3, cm
-1) 1723,1685,1621,1597,1568,1496,1453,1442,1392,1286,1267,1156, and 1138.MS (ES) m/e 330,332.C
21H
17NO
3Ultimate analysis:
Calculated value: C76.13; H5.14; N4.23
Measured value: C75.90; H5.20; N4.46 (b) will be with the sodium hydride of 60% concentration in mineral oil (0.79g 19.8mM) adds the 9-[(phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone (2.87g, 8.61mM) solution in the 29ml diox.Stirred reaction mixture 8 minutes, then add the benzene sulfinic acid methyl esters (1.80ml, 13.8mM).The reaction mixture restir after 1.5 hours, is diluted with 43ml diox and 1.13ml acetate.Mixture was refluxed 1 hour, dilute, and extract secondary, use saline water extraction again with saturated sodium bicarbonate with ethyl acetate.Dry (Na
2SO
4) after, under vacuum condition, evaporate, obtain the 4.90g crude product.Again mixture is passed through column chromatography purifying (with toluene/methylene dichloride wash-out) on silica gel, obtains 2.31g (81%) 9-[(3-aminomethyl phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole.
1H NMR (DMSO-d6) δ 10.25 (s, 1H), 7.7 (d, 1H, J=8 Hz), 7.4 (t, 1H, J=8 Hz), 7.4-7.0 (m, 8H), 6.6 (d, 1H, J=8 Hz), 5.6 (s, 2H), and 3.8 (s, 3H) .IR (CHCl
3, cm
-1) 1723,1685,1621,1597,1568,1496,1453,1442,1392,1286,1267,1156, and1138.MS (ES) m/e 330,332.C
21H
17NO
3Ultimate analysis:
Calculated value: C76.13; H5.14; N4.23
Measured value: C75.90; H5.20; N4.46C, 9-[(phenyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(phenyl) methyl]-(200mg, 0.6mM) solution in 4ml methyl alcohol and the dense ammonium hydroxide water of 40ml carried out sonication 30 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer three times, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 50mg (26%) 9-[(phenyl) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.85 (dd, 1H, J=1 and 8 Hz), 7.5-7.1 (m, 9H), 6.6 (d, 1H, J=8 Hz), and 5.8 (s, 2H) .IR (KBr, cm
-1) 3428,3198,3063,1631,1599,1579,1562,1496,1442,1330,1261,1215,775, and 697.MS (ES) m/e 315,317.C
20H
16N
2O
2Ultimate analysis:
Calculated value: C75.95; H5.06; N8.86
Measured value: C74.88; H5.40; N7.78D, the 9-[(phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under 0 ℃, 40% methyl alcohol is closed Triton B (0.11ml 0.24mM) adds the 9-[(phenyl) methyl]-(70mg is 0.22mM) in the solution that forms in 20ml DMF for 4-hydroxyl-5-formamyl carbazole.After 15 minutes, (70mg 0.44mM), and at room temperature stirred the mixture that generates 5 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate,, use dried over mgso, filter and concentrate with 1N HCl, water and saturated brine washing.With resistates with use 45mg (0.14mM[amounts to 0.36mM]) 9-[(phenyl) methyl]-crude product that the 4-hydroxyl-5-formamyl carbazole obtains in the same way merges.With the resistates after merging on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 76mg (54%) the 9-[(phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (DMSO-d6) δ 7.65 (d, 1H, J=8 Hz), 7.5 (br s, 1H), 7.4-7.15 (m, 9H), 7.1 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 5.7 (s, 2H), 4.9 (s, 2H), and 3.75 (s, 3H) .IR (KBr, cm
-1) 3367,3200,1760,1643,1579,1496,1452,1427,1216,1157,772, and 716.MS (FD) m/e 388.C
23H
20N
2O
4Ultimate analysis:
Calculated value: C71.13; H5.15; N7.22
Measured value: C70.77; H5.49; N6.79E, the 9-[(phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will the 9-[(phenyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (10.1mg, 0.025mM) and the solution stirring that in 3ml ethanol, forms of 0.025ml (0.025mM) and 1N sodium hydroxide 16 hours.Gather up the white precipitate of generation by filtration, dry under vacuum condition then with the small amount of ethanol washing, obtain 7.1mg (70%) the 9-[(phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H NMR (DMSO-d6) δ 7.6 (d, 1H, J=8 Hz), 7.5-7.05 (m, 11H), 6.55 (d, 1H, J=8 Hz), 5.75 (s, 2H), and 4.3 (s, 2H) .IR (KBr, cm
-1) 3471,1657,1615,1591,1496,1453,1412,1330,1272, and1151.MS (ES) m/e 373,375,397.C
22H
17N
2O
4The Na ultimate analysis:
Calculated value: C66.67; H4.29; N7.07
Measured value: C66.75; H4.55; N6.83 embodiment 25{9-[(3-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid
A, 9-[(3-fluorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
Under 0 ℃, 40% methyl alcohol is closed Triton B, and (2.06ml 4.53mM) slowly splashes into 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (930.0mg, 3.82mM) solution in 5ml DMF.After 5 minutes, (664.0mg 4.59mM), and stirs the mixture that generates 3 hours down at 0 ℃, then, at room temperature stirs 20 hours to add the 3-fluorobenzyl chloride.Mixture is diluted with ethyl acetate,, wash with water three times, with the saturated brine washing once, use anhydrous magnesium sulfate drying, filter and concentrate with 1N HCl washing three times.Again resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 502.3mg (37%) 9-[(3-fluorophenyl) methyl]-5-methoxycarbonyl-1, the yellow foam of 2-dihydro carbazole-4 (3H)-ketone.
1H NMR (CDCl
3) δ 7.4-7.2 (m, 4H), 6.9 (m, 1H), 6.7 (m, 2H), 5.35 (s, 2H), 4.05 (s, 3H), 2.9 (t, 2H, J=6 Hz), 2.65 (t, 2H, J=6 Hz), and 2.3 (m, 2H) .IR (CHCl
3, cm
-1) 3050,2950,1725,1654,1464,1451,1440,1288 and 1119.MS (ES) m/e 350,352.C
21H
18NO
3The F ultimate analysis:
Calculated value: C71.78; H5.16; N3.99
Measured value: C72.00; H4.95; N4.11B, 9-[(3-fluorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(3-fluorophenyl) methyl]-5-methoxycarbonyl-1, (434.0mg is 1.23mM) with 2 for 2-dihydro carbazole-4 (3H)-ketone, 3-two chloro-5,6-dicyano-1, (324.0mg, 1.42mM) solution that forms in 20ml toluene stirred 5 hours between 70-80 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 137.0mg (32%) 9-[(3-fluorophenyl) methyl]-the yellow foam of 4-hydroxy-5-methyl ester group carbazole.
1H NMR (DMSO-d6) δ 10.2 (s, 1H), 7.7d, 1H, J=8 Hz), (7.4 t, 1H, J=8 Hz), 7.3 (m, 2H), 7.2 (d, 1H, J=8Hz), (7.1 d, 1H, J=8 Hz), 7.05-6.85 (m, 3H), 6.6 (d, 1H, J=8Hz), 5.65 (s, 2H), and 3.85 (s, 3H) .IR (CHCl
3, cm
-1) 3200 (br), 1687,1597,1452,1442,1285, and 1267.MS (ES) m/e348,350.C
21H
16NO
3The F ultimate analysis:
Calculated value: C72.20; H4.62; N4.01
Measured value: C72.30; H4.66; N4.04C, 9-[(3-fluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(3-fluorophenyl) methyl]-(130.8mg, 0.37mM) solution in 5ml THF and the dense ammonium hydroxide water of 20ml carried out sonication 5 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer secondary, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 57.4mg (45%) 9-[(3-fluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.8 (dd, 1H, J=1 and 8 Hz), 7.5 (m, 2H), 7.3 (m, 2H), 7.15-7.0 (m, 2H), 6.95 (d, 1H, J=8 Hz), (6.85 d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), and 5.7 (s, 2H) .IR (CHCl
3, cm
-1) 3431,3200 (br), 1628,1614,1600,1580,1546,1488,1448,1329,1261, and 776.MS (ES) m/e 333,335.C
20H
15N
2O
2The F ultimate analysis:
Calculated value: C71.85; H4.52; N8.38
Measured value: C74.45; H6.01; N8.48D, the 9-[(3-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester
Under the room temperature, 40% methyl alcohol is closed Triton B (0.086ml 0.19mM) adds the 9-[(3-fluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole (51.9mg, 0.155mM) solution that in 3ml DMF, forms.After 3 minutes, (87.8mg 0.44mM), and at room temperature stirred the mixture that generates 5 hours to add the monobromo-acetic acid tert-butyl ester.Mixture is diluted with ethyl acetate, and dried over mgso is used in water and saturated brine washing four times, filters and concentrates.With resistates on silica gel by column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution), obtain 44.0mg (63%) the 9-[(3-fluorophenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid tert-butyl ester white solid.
1H NMR (DMSO-d6) δ 7.6 (d, 1H, J=8 Hz), 7.5-6.8 (m, 10H), 6.55 (d, 1H, J=8 Hz), 5.7 (s, 2H), 4.8 (s, 2H), and 1.45 (s, 9H) .IR (CHCl
3, cm
-1) 3450,3400,1746,1674,1592,1457,1369, and 1151.MS (FD) m/e 448.C
26H
25N
2O
4The F ultimate analysis:
Calculated value: C69.63; H5.62; N6.25
Measured value: C69.35; H5.44; N6.23E, the 9-[(3-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid
At room temperature, incite somebody to action the 9-[(3-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester (40.0mg, the solution stirring that 0.089mM) in the 2ml trifluoroacetic acid, forms 5 hours.Under vacuum condition, remove and desolvate, resistates is developed with ether, dry under vacuum condition then, obtain 35.0mg (100%) the 9-[(3-fluorophenyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid white powder.
1H NMR (DMSO-d6) δ 13.0 (br s, 1H), 7.75 (s, 1H), 7.6 (d, 1H, J=8 Hz), 7.5-7.25 (m, 5H), 7.2-6.8 (m, 4H), 6.6 (d, 1H, J=8 Hz), 5.7 (s, 2H), and 4.8 (s, 2H) .IR (KBr, cm
-1) 3423,3400,1736,1637,1615,1589,1499,1487,1450,1436,1331,1250, and 1156.MS (ES) m/e 391,393.C
22H
17N
2O
4The F ultimate analysis:
Calculated value: C67.34; H4.37; N7.14
Measured value: C67.63; H4.22; N7.35 embodiment 26{9-[(3-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid
A, 9-[(3-chloro-phenyl-) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
At room temperature, will be by 5-methoxycarbonyl-1, and 2-dihydro-9H-carbazole-4 (3H)-ketone (527.0mg, 2.17mM), 3-chlorine bromotoluene (802.2mg, 3.90mM), the sodium iodide of catalytic amount (approximately 1mg) and salt of wormwood (500.0mg, the suspension that 3.62mM) forms stirring 150 hours.Mixture is diluted with ethyl acetate, wash with water five times, with the saturated brine washing once, use anhydrous magnesium sulfate drying, filter and concentrate.Again resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 537.1mg (67%) 9-[(3-chloro-phenyl-) methyl]-5-methoxycarbonyl-1, the yellow foam of 2-dihydro carbazole-4 (3H)-ketone.
1H NMR (CDCl
3) δ 7.5-7.2 (m, 5H), 7.1 (s, 1H), 6.85 (m, 1H), 5.35 (s, 2H), 4.05 (s, 3H), 2.9 (t, 2H, J=6 Hz), 2.65 (t, 2H, J=6 Hz), and2.3 (m, 2H) .IR (CHCl
3, cm
-1) 3050,2950,1725,1654,1464,1444,1432,1288 and 1120.MS (ES) m/e 366,368,370.C
21H
18NO
3The Cl ultimate analysis:
Calculated value: C68.57; H4.93; N3.81
Measured value: C68.61; H4.92; N3.70B, 9-[(3-chloro-phenyl-) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(3-chloro-phenyl-) methyl]-5-methoxycarbonyl-1, (480.5mg is 1.31mM) with 2 for 2-dihydro carbazole-4 (3H)-ketone, 3-two chloro-5,6-dicyano-1, (325.7mg, 1.43mM) solution that forms in 50ml toluene stirred 3 hours between 70-80 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 172.6mg (36%) 9-[(3-chloro-phenyl-) methyl]-the yellow foam of 4-hydroxy-5-methyl ester group carbazole.
1H NMR (CDCl
3) δ 10.4 (s, 1H), 8.05 (d, 1H, J=8 Hz), 7.6 (d, 1H, J=8 Hz), 7.4 (m, 2H), 7.3-7.1 (m, 3H), 6.9-6.7 (m, 3H), 5.55 (s, 2H), and 4.15 (s, 3H) .IR (CHCl
3, cm
-1) 3200 (br), 1684,1598,1442,1428,1331,1285, and1267.MS (ES) m/e 364,366,368.C
21H
16NO
3The Cl ultimate analysis:
Calculated value: C68.95; H4.41; N3.83
Measured value: C69.23; H4.52; N3.88C, 9-[(3-chloro-phenyl-) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(3-chloro-phenyl-) methyl]-(156.2mg, 0.43mM) solution in 5ml THF and the dense ammonium hydroxide water of 20ml carried out sonication 5 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer secondary, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 69.7mg (47%) 9-[(3-chloro-phenyl-) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.8 (dd, 1H, J=1 and 8 Hz), 7.45 (m, 2H), 7.3 (m, 3H), 7.2 (s, 1H), 7.1 (d, 1H, J=8 Hz), 6.95 (s, 1H), 6.6 (d, 1H, J=8Hz), and 5.7 (s, 2H) .IR (CHCl
3, cm
-1) 3433,3202 (br), 1630,1600,1580,1564,1433,1330,1261, and 776.MS (ES) m/e349,351,353.C
20H
15N
2O
2The Cl ultimate analysis:
Calculated value: C68.48; H4.31; N7.99
Measured value: C68.64; H4.55; N7.93D, the 9-[(3-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester
Under the room temperature, 40% methyl alcohol is closed Triton B (0.053ml 0.12mM) adds the 9-[(3-chloro-phenyl-) methyl]-4-hydroxyl-5-formamyl carbazole (33.2mg, 0.12mM) solution that in 2ml DMF, forms.After 3 minutes, (53.8mg 0.27mM), and at room temperature stirred the mixture that generates 20 hours to add the monobromo-acetic acid tert-butyl ester.Mixture is diluted with ethyl acetate, wash with water four times, with the saturated brine washing once, use dried over mgso, filter and concentrate.With resistates on silica gel by column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution), obtain 42.1mg (95%) the 9-[(3-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid tert-butyl ester white solid.
1H NMR (DMSO-d6) δ 7.6 (d, 1H, J=8 Hz), 7.5-6.8 (m, 10H), 6.55 (d, 1H, J=8 Hz), 5.7 (s, 2H), 4.8 (s, 2H), and 1.45 (s, 9H). IR (CHCl
3, cm
-1) 3450,3400,1744,1676,1591,1457,1369, and 1150.MS (FD) m/e 464,466.C
26H
25N
2O
4The Cl ultimate analysis:
Calculated value: C67.17; H5.42; N6.03
Measured value: C67.17; H5.65; N5.97E, the 9-[(3-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid
At room temperature, incite somebody to action the 9-[(3-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester (35.6mg, the solution stirring that 0.077mM) in the 2ml trifluoroacetic acid, forms 6 hours.Under vacuum condition, remove and desolvate, resistates is developed with ethyl acetate, dry under vacuum condition then, obtain 31.4mg (100%) the 9-[(3-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid white powder.
1H NMR (DMSO-d6) δ 13.0 (br s, 1H), 7.75 (s, 1H), 7.6 (d, 1H, J=8 Hz), 7.4-7.25 (m, 7H), 7.2 (d, 1H, J=8 Hz), 7.0 (br t, 1H), 6.6 (d, 1H, J=8 Hz), 5.7 (s, 2H), and 4.8 (s, 2H) .IR (KBr, cm
-1) 3456,3416,3335,1735,1638,1617,1580,1499,1452,1431,1431,1329,1255,1157,772,764, and 717.MS (ES) m/e 407,409,411.C
22H
17N
2O
4The Cl ultimate analysis:
Calculated value: C64.63; H4.19; N6.85
Measured value: C64.55; H4.12; N6.74 embodiment 27{9-[(3-Phenoxyphenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid
A, 9-[(3-Phenoxyphenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
Under 25 ℃, 40% methyl alcohol is closed Triton B, and (1.53ml 3.4mM) slowly splashes into 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (554.6mg, 2.28mM) solution in 5ml DMF.After 5 minutes, (748.0mg 3.42mM), and at room temperature stirred the mixture that generates 24 hours to add 3-phenoxy benzyl chlorine.Mixture is diluted with ethyl acetate,, wash with water three times, with the saturated brine washing once, use anhydrous magnesium sulfate drying, filter and concentrate with 1N HCl washing three times.Again resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 563.6mg (58%) 9-[(3-Phenoxyphenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone goldenrod oily matter.
1H NMR (DMSO-d6) δ 7.7 (dd, 1H, J=1 and 8 Hz), 7.4-7.2 (m, 6H), 7.1 (t, 1H, J=8 Hz), 6.95 (m, 2H), 6.8-6.7 (m, 2H), 5.55 (s, 2H), 3.75 (s, 3H), (3.0 t, 2H, J=6 Hz), 2.45 (t, 2H, J=6 Hz), and 2.1 (m, 2H) .IR (CHCl
3, cm
-1) 3050,2950,1725,1653,1585,1487,1465,1288,1252, and 1119.MS (ES) m/e 426.C
27H
23NO
4Ultimate analysis:
Calculated value: C76.22; H5.45; N3.29
Measured value: C76.21; H5.35; N3.36B, 9-[(3-Phenoxyphenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(3-Phenoxyphenyl) methyl]-5-methoxycarbonyl-1, (544.5mg is 1.28mM) with 2 for 2-dihydro carbazole-4 (3H)-ketone, 3-two chloro-5,6-dicyano-1, (337.5mg, 1.48mM) solution that forms in 20ml toluene stirred 4 hours between 70-80 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 107.0mg (20%) 9-[(3-Phenoxyphenyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow powder.
1H NMR (DMSO-d6) δ 10.4 (s, 1H), 7.7 (d, 1H, J=8 Hz), 7.4-6.7 (m, 13H), 6.55 (d, 1H, J=8 Hz), 5.65 (s, 2H), and 3.85 (s, 3H) .IR (CHCl
3, cm
-1) 3200 (br), 1687,1597,1584,1487,1441,1332,1284,1267, and 1252.MS (ES) m/e 422,424.C
27H
21NO
4Ultimate analysis:
Calculated value: C76.58; H5.00; N3.31
Measured value: C76.68; H5.20; N3.40C, 9-[(3-Phenoxyphenyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(3-Phenoxyphenyl) methyl]-(100.0mg, 0.24mM) solution in 5ml THF and the dense ammonium hydroxide water of 20ml carried out sonication 24 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer secondary, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 41.0mg (43%) 9-[(3-Phenoxyphenyl) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.8 (dd, 1H, J=1 and 8 Hz), 7.5-6.7 (m, 13H), 6.6 (d, 1H, J=8 Hz), (s, 2H) .MS (ES) m/e 407,409.C for and 5.7
26H
20N
2O
3Ultimate analysis:
Calculated value: C76.46; H4.94; N6.86
Measured value: C76.66; H5.29; N6.58D, the 9-[(3-Phenoxyphenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester
Under the room temperature, 40% methyl alcohol is closed Triton B (0.054ml 0.12mM) adds the 9-[(3-Phenoxyphenyl) methyl]-4-hydroxyl-5-formamyl carbazole (39.5mg, 0.10mM) solution that in 3ml DMF, forms.After 3 minutes, (54.8mg 0.27mM), and at room temperature stirred the mixture that generates 5 hours to add the monobromo-acetic acid tert-butyl ester.Mixture is diluted with ethyl acetate, wash with water four times, with the saturated brine washing once, use dried over mgso, filter and concentrate.With resistates on silica gel by column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution), obtain 33.0mg (65%) the 9-[(3-Phenoxyphenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid tert-butyl ester white solid.
1H NMR (DMSO-d6) δ 7.6 (d, 1H, J=8 Hz), 7.5-6.8 (m, 15H), 6.55 (d, 1H, J=8 Hz), 5.7 (s, 2H), 4.8 (s, 2H), and 1.45 (s, 9H) .IR (KBr, cm
-1) 3450,1748,1670,1582,1486,1246,1225, and 1151.MS (ES) m/e 523.C
32H
30N
2O
5Ultimate analysis:
Calculated value: C73.55; H5.79; N5.36
Measured value: C73.84; H5.83; N5.30E, the 9-[(3-Phenoxyphenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid
At room temperature, incite somebody to action the 9-[(3-Phenoxyphenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester (30.0mg, the solution stirring that 0.063mM) in the 2ml trifluoroacetic acid, forms 6 hours.Under vacuum condition, remove and desolvate, resistates is dry under vacuum condition, obtain 30.0mg (100%) the 9-[(3-Phenoxyphenyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid white powder.
1H NMR (DMSO-d6) δ 13.0 (br s, 1H), 7.75 (s, 1H), 7.6 (d, 1H, J=8 Hz), 7.5-6.8 (m, 14H), 6.6 (d, 1H, J=8 Hz), 5.7 (s, 2H), and 4.8 (s, 2H) .IR (KBr, cm
-1) 3450,3400,1740,1651,1592,1585,1487,1457,1441,1329,1250, and 1158.MS (ES) m/e 465,467.C
28H
22N
2O
5Ultimate analysis:
Calculated value: C72.09; H4.75; N6.00
Measured value: C67.65; H4.64; N6.02 embodiment 28{9-[(2-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid
A, 9-[(2-fluorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
Under 25 ℃, 40% methyl alcohol is closed Triton B, and (2.82ml 6.2mM) slowly splashes into 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (1.27g, 5.22mM) solution in 10ml DMF.After 5 minutes, (1.19g 6.2mM), and at room temperature stirred the mixture that generates 17 days to add the 2-fluoro benzyl bromide.Mixture is diluted with ethyl acetate, wash with water five times, with the saturated brine washing once, use anhydrous magnesium sulfate drying, filter and concentrate.Again resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 1.00g (55%) 9-[(2-fluorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone tawny foam.
1H NMR (DMSO-d6) δ 7.7 (dd, 1H, J=1 and 8 Hz), 7.4-7.2 (m, 4H), 7.1 (t, 1H, J=8 Hz), (6.7 t, 1H, J=8 Hz), 5.65 (s, 2H), 3.8 (s, 3H), 3.0 (t, 2H, J=6 Hz), 2.45 (t, 2H, J=6 Hz), and 2.1 (m, 2H) .IR (CHCl
3, cm
-1) 3050,2950,1725,1652,1464,1441,1288 and 1120.MS (ES) m/e 350,352.C
21H
18NO
3The F ultimate analysis:
Calculated value: C71.78; H5.16; N3.99
Measured value: C71.51; H5.08; N3.85B, 9-[(2-fluorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(2-fluorophenyl) methyl]-5-methoxycarbonyl-1, and 2-dihydro carbazole-4 (3H)-ketone (1.00g, 2.85mM) with 2,3-two chloro-5,6-dicyano-1, (800.0mg, 3.51mM) solution that forms in 50ml toluene stirred 6 hours between 70-80 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 250.0mg (25%) 9-[(2-fluorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole dark solid.
1H NMR (DMSO-d6) δ 10.2 (s, 1H), 7.7 (d, 1H, J=8 Hz), 7.4 (t, 1H, J=8 Hz), and 7.3-6.85 (m, 6H), 6.75 (dt, 1H, J=5 and 8 Hz), 6.6 (d, 1H, J=8 Hz), 5.7 (s, 2H), and3.85 (s, 3H) .IR (CHCl
3, cm
-1) 3200 (br), 1686,1598,1490,1442,1285,1268,1230, and 1139.MS (ES) m/e 348,350.C
21H
16NO
3The F ultimate analysis:
Calculated value: C72.20; H4.62; N4.01
Measured value: C71.32; H4.75; N4.11C, 9-[(2-fluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(2-fluorophenyl) methyl]-(237.5mg, 0.68mM) solution in 10ml THF and the dense ammonium hydroxide water of 40ml carried out sonication 20 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer secondary, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 89.7mg (40%) 9-[(2-fluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.8 (dd, 1H, J=1 and 8 Hz), 7.5-6.9 (m, 7H), 6.65 (m, 2H), and 5.75 (s, 2H) .IR (KBr, cm
-1) 3395,3192 (br), 1621,1599,1580,1564,1491,1455,1334,1261, and 774.MS (ES) m/e 333,335.C
20H
15N
2O
2The F ultimate analysis:
Calculated value: C71.85; H4.52; N8.38
Measured value: C72.57; H4.88; N7.84D, the 9-[(2-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.14ml 0.31mM) adds the 9-[(2-fluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole (51.9mg, 0.155mM) solution that in 5ml DMF, forms.After 3 minutes, (110.5mg 0.72mM), and at room temperature stirred the mixture that generates 20 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate, wash with water four times, with the saturated brine washing once, use dried over mgso, filter and concentrate.With resistates on silica gel by column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution), obtain 72.8mg (71%) the 9-[(2-fluorophenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (DMSO-d6) δ 7.65 (d, 1H, J=8 Hz), 7.5 (s, 1H), 7.4-7.2 (m, 5H), 7.15 (s, 1H), 7.1 (d, 1H, J=8 Hz), 7.05 (t, 1H, J=8Hz), (6.7 t, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), 5.7 (s, 2H), 4.85 (s, 2H), and 3.7 (s, 3H) .IR (CHCl
3, cm
-1) 3436,1763,1675,1457,1327,1208,1198,1150,1102,772,756, and719.MS (FD) m/e 407.C
23H
19N
2O
4The F ultimate analysis:
Calculated value: C67.97; H4.71; N6.89
Measured value: C68.00; H4.92; N6.75E, the 9-[(2-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid
Under 50-60 ℃, will the 9-[(2-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (47.9mg, 0.118mM) and the solution sonication that in 10ml methyl alcohol, forms of 0.28ml1N sodium hydroxide 6 hours; At room temperature stirred then 16 hours.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer secondary; organic extracting solution after will merging again washs with saturated brine; use dried over mgso, filter and concentrate, obtain 42.8mg (92%) the 9-[(2-fluorophenyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid white powder.
1HNMR (DMSO-d6) δ 7.75 (s, 1H), 7.6 (d, 1H, J=8 Hz), 7.5-7.25 (m, 6H), 7.15 (d, 1H, J=8 Hz), 7.05 (dt, 1H, J=1 and 8 Hz), (6.75 dt, 1H, J=1 and 8 Hz), (6.65 d, 1H, J=8 Hz), 5.7 (s, 2H), and 4.8 (s, 2H) .IR (KBr, cm
-1) 3428,3400,1737,1635,1617,1583,1572,1500,1491,1453,1434,1330,1248,1158,1098,760, and 714.MS (FD) m/e 392.C
22H
17N
2O
4The F ultimate analysis:
Calculated value: C67.34; H4.37; N7.14
Measured value: C66.65; H4.55; N6.92 embodiment 29{9-[(2-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid
A, 9-[(2-trifluoromethyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
Under-10 ℃, 40% methyl alcohol is closed Triton B, and (2.18ml 4.8mM) slowly splashes into 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (973mg, 4.0mM) solution in 10ml DMF.After 30 minutes, (1.3g 5.2mM), and at room temperature stirred the mixture that generates 23 hours to add 2-(trifluoromethyl) bromotoluene.Mixture is diluted with ethyl acetate, wash with water five times, with the saturated brine washing once, use anhydrous magnesium sulfate drying, filter, concentrate, and dry under vacuum condition, obtain 1.34g (83%) 9-[(2-trifluoromethyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone tawny solid.
1H NMR (CDCl
3) δ 7.7 (d, 1H, J=8 Hz), 7.4-7.1 (m, 5H), 6.4 (d, 1H, J=8 Hz), 5.5 (s, 2H), 4.05 (s, 3H), 2.8 (t, 2H, J=6 Hz), 2.6 (t, 2H, J=6 Hz), and 2.2 (m, 2H) .IR (KBr, cm
-1) 1729 and 1656.MS (ES) m/e 402.C
22H
18NO
3F
3Ultimate analysis:
Calculated value: C65.83; H4.52; N3.49; F14.20
Measured value: C66.07; H4.59; N3.20; F13.95B, 9-[(2-trifluoromethyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(2-trifluoromethyl) methyl]-5-methoxycarbonyl-1, (1.21g is 3.00mM) with 2 for 2-dihydro carbazole-4 (3H)-ketone, 3-two chloro-5,6-dicyano-1, (764mg, 3.3mM) solution that forms in 25ml toluene stirred 7 hours between 80-90 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 340.0mg (28%) 9-[(2-trifluoromethyl) methyl]-4-hydroxy-5-methyl ester group carbazole brown ceramic powder.
1H NMR (CDCl
3) δ 10.4 (s, 1H), 8.0 (d, 1H, J=8 Hz), 7.7 (d, 1H, J=8 Hz), 7.5-7.2 (m, 5H), 6.85 (m, 2H), 6.45 (d, 1H, J=8 Hz), 5.7 (s, 2H), and 4.1 (s, 3H) .IR (CHCl
3, cm
-1) 3200 (br) and 1677.MS (ES) m/e 398,400.C
22H
16NO
3F
3Ultimate analysis:
Calculated value: C66.17; H4.04; N3.51; F14.27
Measured value: C66.93; H4.06; N3.54; F14.00C, 9-[(2-trifluoromethyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(2-trifluoromethyl) methyl]-(310mg, 0.77mM) solution in 5ml THF and the dense ammonium hydroxide water of 20ml carried out sonication 25 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer secondary, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 145mg (49%) 9-[(2-trifluoromethyl) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.8 (d, 1H, J=8 Hz), and 7.6-7.2 (m, 6H), 6.85 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.25 (d, 1H, J=8 Hz), and 5.8 (s, 2H) .IR (KBr, cm
-1) 3460,3360, and 1589.MS (ES) m/e 383,385.C
21H
15N
2O
2F
3Ultimate analysis:
Calculated value: C65.62; H3.93; N7.29; F14.83
Measured value: C65.65; H3.94; N7.51; F14.94D, the 9-[(2-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.18ml 0.4mM) adds the 9-[(2-trifluoromethyl) methyl]-4-hydroxyl-5-formamyl carbazole (120mg, 0.31mM) solution that in 5ml DMF, forms.After 15 minutes, (98.5mg 0.62mM), and at room temperature stirred the mixture that generates 4.5 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate, and water, 1N HCl, water, saturated sodium bicarbonate and saturated brine wash four times, use dried over mgso, filter and concentrate.With resistates on silica gel by column chromatography purifying (with dichloromethane/ethyl acetate/THF gradient elution), obtain 95mg (67%) the 9-[(2-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (CDCl
3) δ 7.7 (d, 1H, J=8 Hz), and 7.5-7.2 (m, 6H), 6.95 (d, 1H, J=8 Hz), (6.6 d, 1H, J=8 Hz), 6.45 (d, 1H, J=8 Hz), 6.3 (brs, 1H), 6.1 (br s, 1H), 5.7 (s, 2H), 4.9 (s, 2H), and 3.9 (s, 3H) .IR (CHCl
3, cm
-1) 1763 and 1674.MS (ES) m/e 457.C
24H
19N
2O
4F
3Ultimate analysis:
Calculated value: C63.16; H4.20; N6.14
Measured value: C61.82; H4.31; N5.86E, the 9-[(2-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid
Under 50-60 ℃, will the 9-[(2-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (70mg, 0.153mM) and the solution sonication that in 5ml methyl alcohol, forms of 0.21ml (0.21mM) 1N sodium hydroxide 23 hours.Under vacuum condition, remove methyl alcohol, and mixture is acidified to pH with 1N HCl is 1.6.By filter will generate white precipitate collect; water, small amount of methanol and ether washing; dry under vacuum condition then, obtain 59mg (88%) the 9-[(2-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid white powder.
1HNMR (DMSO-d6) δ 13.0 (br s, 1H), 7.8 (d, 1H, J=8 Hz), 7.75 (s, 1H), 7.5-7.3 (m, 6H), 7.1 (d, 1H, J=8 Hz), 7.05 (d, 1H, J=8 Hz), (6.6 d, 1H, J=8 Hz), (6.3 d, 1H, J=8 Hz), 5.8 (s, 2H), and 4.8 (s, 2H) .IR (KBr, cm
-1) 1737 and 1635.MS (ES) m/e 441,443.C
23H
17N
2O
4F
3Ultimate analysis:
Calculated value: C62.45; H3.87; N6.33; F12.88
Measured value: C60.86; H3.89; N6.08; F12.59 embodiment 30{9-[(2-benzyl phenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 2-benzyl bromotoluene
Under 0 ℃, (22.1mM) solution in the 30ml tetracol phenixin slowly splashes into 2-benzyl benzylalcohol (1.98g is 10mM) in the solution in the 70ml tetracol phenixin for 2.1ml, 6.0g with phosphorus tribromide.This mixture was stirred 2 hours down at 0 ℃, then at room temperature stirred 2 hours.Under vacuum condition,, resistates is diluted with ethyl acetate and saturated sodium bicarbonate aqueous solution except that after desolvating.With organic layer salt water washing, use dried over mgso, filter and concentrate, obtain 2.6g (99%) 2-benzyl bromotoluene yellow solid.
1H NMR (DMSO-d6) δ 7.5-7.0 (m, 9H), 4.7 (s, 2H), and 4.15 (s, 2H) .IR (CHCl
3, cm
-1) 3065,1601,1495, and 1453.MS (FD) m/e 260,262.C
14H
13The Br ultimate analysis:
Calculated value: C64.37; H4.98; N0.00
Measured value: C65.26; H5.26; N0.00B, 9-[(2-benzyl phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
Under-10 ℃, 40% methyl alcohol is closed Triton B, and (0.95ml 2.1mM) slowly splashes into 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (510mg, 2.1mM) solution in 30ml DMF.After 3 minutes, (548mg 2.1mM), and at room temperature stirred the mixture that generates 6 hours to add 2-benzyl bromotoluene.With ethyl acetate and 1N HCl dilution, wash mixture with water secondary, with the saturated brine washing once, use anhydrous magnesium sulfate drying, filter, concentrate, and dry under vacuum condition.Again resistates is passed through column chromatography purifying (using eluent ethyl acetate) on silica gel, obtains 324mg (36%) 9-[(2-benzyl phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone tawny solid.
1H NMR (CDCl
3) δ 7.45-7.0 (m, 10H), 6.9 (d, 1H, J=8 Hz), 6.3 (d, 1H, J=8 Hz), 5.2 (s, 2H), 4.15 (s, 2H), 4.05 (s, 3H), 2.5 (m, 4H), and 2.1 (m, 2H) .IR (KBr, cm
-1) 1726,1653,1466,1443,1411,1283,1200,1119, and 749.MS (ES) m/e 422,424.C
28H
25NO
3Ultimate analysis:
Calculated value: C79.43; H5.91; N3.31
Measured value: C79.58; H5.94; N3.32C, 9-[(2-benzyl phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(2-benzyl phenyl) methyl]-5-methoxycarbonyl-1, and 2-dihydro carbazole-4 (3H)-ketone (480mg, 1.14mM) with 2,3-two chloro-5,6-dicyano-1, (250mg, 5.0mM) solution that forms in 30ml toluene stirred 5 hours between 80-90 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the dichloromethane/ethyl acetate wash-out) on silica gel, obtains 166mg (35%) 9-[(2-benzyl phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1H NMR (CDCl
3) δ 10.4 (s, 1H), 8.0 (d, 1H, J=8 Hz), 7.4-7.0 (m, 11H), 6.8 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.4 (d, 1H, J=8 Hz), 5.4 (s, 2H), 4.25 (s, 2H), and4.1 (s, 3H) .IR (CHCl
3, cm
-1) 1684,1597,1495,1452,1442,1333,1284,1269, and 1140.MS (ES) m/e 420,422.D, 9-[(2-benzyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(2-benzyl phenyl) methyl]-(166mg, 0.39mM) solution in 8ml THF and the dense ammonium hydroxide water of 30ml carried out sonication 30 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer secondary, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (using eluent ethyl acetate) on silica gel, obtains 70mg (44%) 9-[(2-benzyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (CDCl
3) δ 8.0 (d, 1H, J=8 Hz), 7.4-7.0 (m; 12H), 6.8 (d, 1H, J=8 Hz); (6.6 d, 1H, J=8 Hz), 6.5 (m; 1H), 6.4 (m, 1H), 5.8 (s; 1H), 5.4 (s, 2H); and 4.2 (s, 2H) .MS (ES) m/e 405,407.E, the 9-[(2-benzyl phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under 25 ℃, 40% methyl alcohol is closed Triton B (0.12ml 0.26mM) adds the 9-[(2-benzyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole (70mg, 0.17mM) solution that in 10ml DMF, forms.After 3 minutes, (55mg 0.34mM), and at room temperature stirred the mixture that generates 25 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate,, use dried over mgso, filter and concentrate with 1N HCl, water and saturated brine washing.With resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 60mg (73%) the 9-[(2-benzyl phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (CDCl
3) δ 7.4-7.00 (m, 14H), 6.65 (d, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), 6.4 (d, 1H, J=8 Hz), 5.4 (s, 2H), 4.95 (s, 2H), 4.2 (s, 2H), and 3.80 (s, 3H) .IR (KBr, cm
-1) 3414,3186,1759,1625,1583,1500,1452,1424,1340,1325,1213,1199, and 1108.MS (ES) m/e 477,479.C
30H
26N
2O
4Ultimate analysis:
Calculated value: C75.31; H5.44; N5.86
Measured value: C75.08; H5.61; N5.70F, the 9-[(2-benzyl phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will the 9-[(2-benzyl phenyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (16.2mg, 0.034mM) and the solution stirring that in 3ml ethanol, forms of 0.034ml (0.034mM) 1N sodium hydroxide 16 hours.Gather up the white precipitate of generation by filtration, it washed with small amount of ethanol, dry under vacuum condition then, obtain 7.1mg (70%) the 9-[(2-benzyl phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H NMR (DMSO-d6) δ 7.5-6.8 (m, 14H), 6.65 (d, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), 6.05 (d, 1H, J=8 Hz), 5.55 (s, 2H), 4.35 (s, 2H), and 4.3 (s, 2H) .IR (CHCl
3, cm
-1) 1666,1616,1495,1452, and 1422.MS (ES) m/e 463,465.C
29H
23N
2O
4The Na ultimate analysis:
Calculated value: C71.60; H4.73; N5.76
Measured value: C64.68; H4.79; N5.08 embodiment 31{9-[(3-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 9-[(3-trifluoromethyl) methyl]-5-methoxycarbonyl-l, 2-dihydro carbazole-4 (3H)-ketone
Under-10 ℃, 40% methyl alcohol is closed Triton B, and (2.18ml 4.8mM) slowly splashes into 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (973mg, 4.0mM) solution in 10ml DMF.After 30 minutes, add 3-(trifluoromethyl) benzyl chloride (1.53g, 6.0mM) and sodium iodide (900mg 6.0mM), and at room temperature stirred the mixture of generation 25 hours.Mixture is diluted with ethyl acetate, and water, 1N HCl, water, saturated sodium bicarbonate and saturated brine wash five times, use anhydrous magnesium sulfate drying, filter, concentrate, and dry under vacuum condition.Again resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 1.02g (63%) 9-[(3-trifluoromethyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone tawny solid.
1H NMR (CDCl
3) δ 7.6 (d, 1H, J=8 Hz), 7.45-7.2 (m, 5H), 7.0 (d, 1H, J=8 Hz), 5.4 (s, 2H), 4.05 (s, 3H), 2.85 (t, 2H, J=6Hz), 2.6 (t, 2H, J=6 Hz), and 2.2 (m, 2H) .IR (KBr, cm
-1) 1727 and 1652.MS (Es) m/e 400,402.C
22H
18NO
3F
3Ultimate analysis:
Calculated value: C65.83; H4.52; N3.49; F14.20
Measured value: C65.63; H4.58; N3.39; F14.14B, 9-[(3-trifluoromethyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(3-trifluoromethyl) methyl]-5-methoxycarbonyl-1, (1.21g is 3.00mM) with 2 for 2-dihydro carbazole-4 (3H)-ketone, 3-two chloro-5,6-dicyano-1, (764mg, 3.3mM) solution that forms in 25ml toluene stirred 7 hours between 80-90 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 340.0mg (28%) 9-[(3-trifluoromethyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1H NMR (CDCl
3) δ 10.35 (s, 1H), 8.0 (d, 1H, J=8 Hz), 7.6-7.3 (m, 6H), 7.05 (d, 1H, J=8 Hz), 6.85 (m, 2H), 5.6 (s, 2H), and 4.1 (s, 3H) .IR (CHCl
3, cm
-1) 3378 and 1712.MS (ES) m/e 398,400.C
22H
16NO
3F
3Ultimate analysis:
Calculated value: C66.17; H4.04; N3.51
Measured value: C66.99; H4.12; N3.53C, 9-[(3-trifluoromethyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(3-trifluoromethyl) methyl]-(250mg, 0.625mM) solution in 5ml THF and the dense ammonium hydroxide water of 20ml carried out sonication 30 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer three times, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 120mg (50%) 9-[(3-trifluoromethyl) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.8 (d, 1H, J=8 Hz), 7.6-7.5 (m, 5H), 7.3 (t, 1H, J=8 Hz), (7.15 d, 1H, J=8 Hz), 7.1 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), and 5.8 (s, 2H) .IR (KBr, cm
-1) 3429,3206, and 1630.MS (ES) m/e383,385.C
21H
15N
2O
2F
3Ultimate analysis:
Calculated value: C65.62; H3.93; N7.29
Measured value: C67.50; H4.00; N7.19D, the 9-[(3-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.18ml 0.4mM) adds the 9-[(3-trifluoromethyl) methyl]-4-hydroxyl-5-formamyl carbazole (115mg, 0.3mM) solution that in 5ml DMF, forms.After 15 minutes, (95mg 0.6mM), and at room temperature stirred the mixture that generates 22 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate, and water, 1N HCl, water, saturated sodium bicarbonate and saturated brine wash four times, use dried over mgso, filter and concentrate.With resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 120mg (88%) the 9-[(3-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (CDCl
3) δ 7.5-7.2 (m, 7H), 7.1 (d, 1H, J=8 Hz), 7.0 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.4 (br s, 1H), 6.0 (br s, 1H), 5.55 (s, 2H), 4.9 (s, 2H), and 3.9 (s, 3H) .IR (KBr, cm
-1) 1763 and 1673.MS (ES) m/e 457.C
24H
19N
2O
4F
3Ultimate analysis:
Calculated value; C63.16; H4.20; N6.14
Measured value: C61.37; H4.19; N5.77E, the 9-[(3-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will the 9-[(3-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (9lmg, 0.153mM) and the solution stirring that in 8ml ethanol, forms of 0.22ml (0.22mM) 1N sodium hydroxide 17 hours.Under vacuum condition, remove ethanol; gather up the white precipitate of generation by filtration; it is washed with small amount of ethanol and ether; dry under vacuum condition then, obtain 75mg (81%) the 9-[(3-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H NMR (DMSO-d6) δ 7.65 (s, 1H), 7.6 (m, 4H), 7.45 (t, 1H, J=8 Hz), 7.35 (t, 1H, J=8 Hz), (7.3 t, 1H, J=8 Hz), 7.2 (d, 1H, J=8 Hz), 7.1 (d, 1H, J=8 Hz), 7.05 (d, 1H, J=8 Hz), 6.5 (d, 1H, J=8 Hz), 5.75 (s, 2H), and 4.3 (s, 2H) .IR (KBr, cm
-1) 1665 and 1618.MS (ES) m/e 441,443.C
23H
16N
2O
4F
3The Na ultimate analysis:
Calculated value: C59.49; H3.47; N6.03
Measured value: C60.69; H3.78; N5.75 embodiment 32{9-[(1-naphthyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 9-[(1-naphthyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
Under 25 ℃, 40% methyl alcohol is closed Triton B, and (1.6ml 3.6mM) slowly splashes into 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (870mg, 3.6mM) solution in 30ml DMF.After 5 minutes, add 1 chloromethyl naphthalene (642mg, 3.6mM) and sodium iodide (450mg 3.0mM), and at room temperature stirred the mixture of generation 25 hours.Mixture is diluted with ethyl acetate, and water, 1N HCl, water, saturated sodium bicarbonate and saturated brine wash five times, use anhydrous magnesium sulfate drying, filter, concentrate, and dry under vacuum condition.Again resistates is passed through column chromatography purifying (using eluent ethyl acetate) on silica gel, obtains 560mg (41%) 9-[(1-naphthyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone yellow solid.
1H NMR (CDCl
3) δ 8.0 (d, 1H, J=8Hz), 7.9 (d, 1H, J=8 Hz), (7.7 d, 1H, J=8 Hz), 7.6 (t, 1H, J=8 Hz), (7.55 t, 1H, J=8 Hz), 7.35 (d, 1H, J=8 Hz), 7.15-7.05 (m, 3H), 6.4 (d, 1H, J=8 Hz), 5.8 (s, 2H), 4.05 (s, 3H), 2.8 (t, 2H, J=6 Hz), (2.55 t, 2H, J=6 Hz), and 2.2 (m, 2H) .IR (KBr, cm
-1) 1721,1646,1464,1448,1438,1285,1122,796, and 761.MS (ES) m/e 382,384.C
25H
21NO
3Ultimate analysis:
Calculated value: C78.33; H5.48; N3.66
Measured value: C76.28; H5.46; N3.93B, 9-[(1-naphthyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(1-naphthyl) methyl]-5-methoxycarbonyl-1, and 2-dihydro carbazole-4 (3H)-ketone (540mg, 1.4mM) with 2,3-two chloro-5,6-dicyano-1, (304mg, 1.33mM) solution that forms in 30ml toluene stirred 5 hours between 80-90 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using eluent ethyl acetate) on silica gel, obtains 240.0mg (45%) 9-[(1-naphthyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1HNMR (DMSO-d6) δ 10.25 (s, 1H), 8.35 (d, 1H, J=8 Hz), (8.0 d, 1H, J=8 Hz), 7.8 (d, 1H, J=8 Hz), and 7.6-7.1 (m, 7H), 6.9 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.3 (d, 1H, J=8 Hz), 6.15 (s, 2H), and 3.8 (s, 3H) .IR (CHCl
3, cm
-1) 1685,1598,1442,1269, and 1140.MS (ES) m/e 380,382.C
25H
19NO
3Ultimate analysis:
Calculated value: C78.74; H4.99; N3.67
Measured value: C78.67; H5.14; N3.54C, 9-[(1-naphthyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(1-naphthyl) methyl]-(210mg, 0.55mM) solution in 10ml THF and the dense ammonium hydroxide water of 30ml carried out sonication 20 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer three times, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (using the hexane/ethyl acetate gradient elution) on silica gel, obtains 80mg (40%) 9-[(1-naphthyl) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (DMSO-d6) δ 10.55 (s, 1H), 8.8 (br s, 1H); 8.4 (br s, 1H), 8.35 (d, 1H; J=8 Hz), 7.95 (d, 1H, J=8 Hz); (7.8 d, 1H, J=8 Hz), 7.65 (m; 4H), 7.45 (m, 2H); (7.25 t, 1H, J=8 Hz); (7.15 t, 1H, J=8 Hz); (6.9 d, 1H, J=8 Hz); (6.6 d, 1H, J=8 Hz); and 6.2 (s, 2H) .MS (ES) m/e 365,367.D, the 9-[(1-naphthyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.2ml 0.26mM) adds the 9-[(1-naphthyl) methyl]-4-hydroxyl-5-formamyl carbazole (80mg, 0.22mM) solution that in 7ml DMF, forms.After 15 minutes, (40mg 0.3mM), and at room temperature stirred the mixture that generates 3 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate, wash secondary with water, with the saturated brine washing once, use dried over mgso, filter and concentrate.With resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 81mg (85%) the 9-[(1-naphthyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (CDCl
3) δ 8.2 (d, 1H, J=8 Hz), 8.05 (d, 1H, J=8 Hz), 7.85-7.0 (m, 11H), 6.65 (d, 1H, J=8 Hz), 6.3 (d, 1H, J=8 Hz), 6.2 (s, 2H), 4.95 (s, 2H), and 3.8 (s, 3H) .IR (KBr, cm
-1) 3364,1739,1630,1582,1500,1455,1285,1232,1153, and 774.MS (FD) m/e 438.C
27H
22N
2O
4Ultimate analysis:
Calculated value: C73.97; H5.02; N6.39
Measured value: C71.66; H5.14; N5.96E, the 9-[(1-naphthyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will the 9-[(1-naphthyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (21mg, 0.048mM) and the solution stirring that in 5ml ethanol, forms of 0.05ml (0.05mM) 1N sodium hydroxide 20 hours.Gather up the white precipitate of generation by filtration, it washed with small amount of ethanol, dry under vacuum condition then, obtain 17mg (80%) the 9-[(1-naphthyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H NMR (DMSO-d6) δ 8.4 (d, 1H, J=8 Hz), 8.05 (d, 1H, J=8 Hz), 7.8 (d, 1H, J=8 Hz), 7.75-7.2 (m, 8H), 7.1 (d, 1H, J=8 Hz), 6.95 (d, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), (6.3 d, 1H, J=8 Hz), 6.15 (s, 2H), and 4.4 (s, 2H) .IR (KBr, cm
-1) 1664,1615,1595,1455,1408,1324,1275, and 775.MS (ES) m/e 423,425.C
26H
19N
2O
4The Na ultimate analysis:
Calculated value: C69.96; H4.26; N6.28
Measured value: C67.91; H4.24; N5.76 embodiment 33{9-[(2-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 9-[(2-cyano-phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
Under 25 ℃, 40% methyl alcohol is closed Triton B, and (2.18ml 4.8mM) slowly splashes into 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (973mg, 4.0mM) solution in 10ml DMF.After 10 minutes, (1.0g 5.0mM), and at room temperature stirred the mixture that generates 30 hours to add a-bromo-neighbour-methylbenzene nitrile.Mixture is diluted with ethyl acetate, and water, 1N HCl, water, saturated sodium bicarbonate, water and saturated brine wash five times, use anhydrous magnesium sulfate drying, filter and concentrate.Resistates is with ether and methylene dichloride development, dry under vacuum condition then, obtain 1.31g (91%) 9-[(2-cyano-phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone tawny solid.
1H NMR (CDCl
3) δ 7.75 (dd, 1H, J=1 and 8 Hz), 7.5-7.2 (m, 5H), 6.6 (d, 1H, J=8 Hz), 5.55 (s, 2H), 4.05 (s, 3H), 2.85 (t, 2H, J=6 Hz), 2.6 (t, 2H, J=6Hz), and 2.25 (m, 2H) .IR (KBr, cm
-1) 2222,1711, and 1650.MS (ES) m/e 357,359.C
22H
18N
2O
3Ultimate analysis:
Calculated value: C73.73; H5.06; N7.82
Measured value: C73.62; H5.34; N7.59B, 9-[(2-cyano-phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(2-cyano-phenyl) methyl]-5-methoxycarbonyl-1, and 2-dihydro carbazole-4 (3H)-ketone (1.27g, 3.5mM) with 2,3-two chloro-5,6-dicyano-1, (892mg, 3.85mM) solution that forms in 25ml toluene stirred 7 hours under the backflow situation 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 305mg (24%) 9-[(2-cyano-phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1H NMR (CDCl
3) δ 10.35 (s, 1H), 8.0 (d, 1H, J=8 Hz), 7.75 (d, 1H, J=8 Hz), 7.5-7.2 (m, 5H), 6.85 (m, 2H), 6.6 (d, 1H, J=8 Hz), 5.75 (s, 2H), and 4.1 (s, 3H) .IR (CHCl
3, cm
-1) 3025,2223, and 1686.MS (ES) m/e 355,357.C
22H
16N
2O
3Ultimate analysis:
Calculated value: C74.15; H4.53; N7.86
Measured value: C72.99; H4.41; N7.65C, 9-[(2-cyano-phenyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(2-cyano-phenyl) methyl]-(295mg, 0.83mM) solution in 5ml THF and the dense ammonium hydroxide water of 20ml carried out sonication 22 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer three times, and organic extracting solution water after will merging and saturated brine washing, use dried over mgso, filter and concentrated.Resistates is passed through column chromatography purifying (using the hexane/ethyl acetate gradient elution) on silica gel, obtains 140mg (49%) 9-[(2-cyano-phenyl) methyl]-4-hydroxyl-5-formamyl carbazole tawny solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.9 (d, 1H, J=8 Hz), 7.75 (d, 1H, J=8 Hz), 7.5-7.4 (m, 4H), 7.25 (t, 1H, J=8 Hz), 7.0 (d, 1H, J=8 Hz), (6.6 d, 1H, J=8 Hz), 6.4 (m, 1H), and 5.85 (s, 2H) .IR (KBr, cm
-1) 3448,3356,2225,1628, and 1600.MS. (ES) m/e 340,342.C
21H
15N
3O
2Ultimate analysis:
Calculated value: C73.89; H4.43; N12.31
Measured value: C73.39; H4.56; N13.32D, the 9-[(2-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.24ml 0.53mM) adds the 9-[(2-cyano-phenyl) methyl]-4-hydroxyl-5-formamyl carbazole (140mg, 0.41mM) solution that in 5ml DMF, forms.After 15 minutes, (130mg 0.82mM), and at room temperature stirred the mixture that generates 24 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate, and water, 1N HCl, water, saturated sodium bicarbonate and saturated brine wash four times, use dried over mgso, filter and concentrate.With resistates on silica gel by column chromatography purifying (with dichloromethane/ethyl acetate/THF gradient elution), obtain 116mg (68%) the 9-[(2-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (CDCl
3) δ 7.75 (d, 1H, J=8 Hz), 7.5-7.2 (m, 6H), 6.95 (d, 1H, J=8 Hz), 6.6 (d, 2H, J=8 Hz)), 6.3 (br s, 1H), 6.1 (brs, 1H), 5.75 (s, 2H), 4.9 (s, 2H), and 3.8 (s, 3H) .IR (KBr, cm
-1) 2228,1732, and 1675.MS (ES) m/e 412,414.C
24H
19N
3O
4Ultimate analysis:
Calculated value: C69.72; H4.63; N10.16
Measured value: C70.00; H4.69; N10.32E, the 9-[(2-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will the 9-[(2-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid methyl esters (110mg, 0.266mM) and the suspension that in 5ml ethanol, forms of 0.29ml (0.29mM) 1N sodium hydroxide carried out sonication 2 hours.Gather up the white precipitate of generation by filtration; it is used small amount of ethanol, ether and hexane wash; dry under vacuum condition then, obtain 107mg (95%) the 9-[(2-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H NMR (DMSO-d6) δ 7.9 (d, 1H, J=8 Hz), 7.6 (br s, 1H), 7.5 (d, 1H, J=8 Hz), 7.45-7.4 (m, 3H), 7.35 (t, 1H, J=8 Hz), 7.25 (t, 1H, J=8 Hz), 7.1 (d, 1H, J=8 Hz), 7.05 (d, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), 6.4 (d, 1H, J=8 Hz), 5.8 (s, 2H), and 4.3 (s, 2H) .IR (KBr, cm
-1) 2220,1652, and 1613.MS (ES) m/e 398,400.C
23H
16N
3O
4The Na ultimate analysis:
Calculated value: C65.56; H3.83; N9.97
Measured value: C65.61; H3.71; N9.89 embodiment 34{9-[(3-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid
A, 9-[(3-cyano-phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
Under 25 ℃, with 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (973mg, 4.0mM), between the a-bromo--the methylbenzene nitrile (1.0g, 4.9mM) and salt of wormwood (553mg, the suspension that 4.0mM) forms among the 10ml DMF stirred 24 hours.Mixture is diluted with ethyl acetate, and water, 1N HCl, water, saturated sodium bicarbonate, water and saturated brine wash five times, use anhydrous magnesium sulfate drying, filter and concentrate.Resistates is dry under vacuum condition, obtain 1.18g (82%) 9-[(3-cyano-phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone tawny solid.
1H NMR (CDCl
3) δ 7.65-7.2 (m, 6H), 7.15 (d, 1H, J=8 Hz), 5.4 (s, 2H), 4.05 (s, 3H), 2.85 (t, 2H, J=6 Hz), 2.6 (t, 2H, J=6 Hz), and 2.25 (m, 2H) .IR (KBr, cm
-1) 2226,1729, and 1646.MS (ES) m/e 357,359.C
22H
18N
2O
3Ultimate analysis:
Calculated value: C73.73; H5.06; N7.82
Measured value: C70.18; H4.97; N7.07B, 9-[(3-cyano-phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(3-cyano-phenyl) methyl]-5-methoxycarbonyl-1, and 2-dihydro carbazole-4 (3H)-ketone (1.15g, 3.2mM) with 2,3-two chloro-5,6-dicyano-1, (815mg, 3.52mM) solution that forms in 25ml toluene stirred 2 hours under the backflow situation 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 120mg (10%) 9-[(3-cyano-phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1H NMR (CDCl
3) δ 10.35 (s, 1H), 8.0 (d, 1H, J=8 Hz), 7.6-7.2 (m, 7H), 6.85 (m, 2H), 5.55 (s, 2H), and 4.1 (s, 3H) .IR (KBr, cm
-1) 3063,3025,2234, and 1685.MS (ES) m/e 355,357.C
22H
16N
2O
3Ultimate analysis:
Calculated value: C74.15; H4.53; N7.86
Measured value: C73.36; H4.51; N8.06C, 9-[(3-cyano-phenyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(3-cyano-phenyl) methyl]-(114mg, 0.32mM) solution in 5ml THF and the dense ammonium hydroxide water of 20ml carried out sonication 7 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer three times, and organic extracting solution water after will merging and saturated brine washing, use dried over mgso, filter and concentrated.Resistates is passed through column chromatography purifying (using the hexane/ethyl acetate gradient elution) on silica gel, obtains 40mg (49%) 9-[(3-cyano-phenyl) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), (7.8 d, 1H, J=8 Hz), 7.7 (d, 1H, J=8Hz), 7.6 (s, 1H), 7.5-7.4 (m, 3H), (7.3 t, 1H, J=8 Hz), 7.25 (d, 1H, J=8 Hz), 7.1 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), and 5.75 (s, 2H) .IR (KBr, cm
-1) 3430,3347,2231,1628, and1601.MS (ES) m/e 340,342.C
21H
15N
3O
2Ultimate analysis:
Calculated value: C73.89; H4.43; N12.31
Measured value: C75.20; H4.80; N12.15D, the 9-[(3-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester
Under the room temperature, 40% methyl alcohol is closed Triton B (0.06ml 0.13mM) adds the 9-[(3-cyano-phenyl) methyl]-4-hydroxyl-5-formamyl carbazole (34.1mg, 0.1mM) solution that in 5ml DMF, forms.After 1 minute, (40mg 0.2mM), and at room temperature stirred the mixture that generates 24 hours to add the monobromo-acetic acid tert-butyl ester.Mixture is diluted with ethyl acetate, and water, 1N HCl, water, saturated sodium bicarbonate and saturated brine wash four times, use dried over mgso, filter and concentrate.Resistates is developed with hexane, obtain 51mg (100%) the 9-[(3-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid tert-butyl ester white solid.
1H NMR (CDCl
3) δ 7.55 (d, 1H, J=8 Hz), 7.5-7.2 (m, 7H), 6.95 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.3 (br s, 1H), 6.1 (br s, 1H), 5.5 (s, 2H), 4.8 (s, 2H), and 1.5 (s, 9H) .IR (KBr, cm
-1) 2228,1748, and 1669.MS (ES) m/e 455,456.C
27H
25N
3O
4Ultimate analysis:
Calculated value: C71.19; H5.53; N9.22
Measured value: C70.24; H5.68; N8.96E, the 9-[(3-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid
At room temperature, incite somebody to action the 9-[(3-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester (45mg, the solution stirring that 0.1mM) in the 3ml trifluoroacetic acid, forms 2 hours.Under vacuum condition, remove and desolvate, resistates is with ether-hexane development, dry under vacuum condition then, obtain 41mg (100%) the 9-[(3-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid tawny powder.
1H NMR (DMSO-d6) δ 13.0 (br s, 1H), 7.6-7.3 (m, 10H), 7.1 (d, 1H, J=8 Hz), 6.65 (d, 1H, J=8 Hz), 5.8 (s, 2H), and 4.8 (s, 2H) .IR (KBr, cm
-1) 2226,1733, and1640.MS (ES) m/e 398,400.C
23H
17N
3O
4Ultimate analysis:
Calculated value: C69.17; H4.29; N10.52
Measured value: C66.96; H4.37; N10.03 embodiment 35{9-[(2-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 9-[(2-aminomethyl phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (870mg, 3.58mM), a-bromo-ortho-xylene (662mg, 3.58mM) and salt of wormwood (500mg, the suspension that 3.61mM) forms in 20ml DMF stirred 20 hours.Mixture is diluted with ethyl acetate, and anhydrous magnesium sulfate drying is used in water and saturated brine washing, filters and concentrates, and obtains 1.21g (98%) 9-[(2-aminomethyl phenyl) methyl]-5-methoxycarbonyl-1, the dark-coloured oily matter of 2-dihydro carbazole-4 (3H)-ketone.
1H NMR (DMSO-d6) δ 7.5-7.2 (m, 4H), 7.15 (t, 1H, J=8 Hz), 7.0 (t, 1H, J=8 Hz), (6.15 d, 1H, J=8 Hz), 5.55 (s, 2H), 3.85 (s, 3H), 2.6 (m, 2H), 2.4 (m, 2H), 2.4 (s, 3H), and 2.1 (m, 2H) .IR (CHCl
3, cm
-1) 3010,2952,1724,1671,1653,1604,1460,1444,1290,1174, and1122.MS (ES) m/e 348.5.C
22H
21NO
3Ultimate analysis:
Calculated value: C76.08; H6.05; N4.03
Measured value: C73.33; H6.36; N4.30B, 9-[(2-aminomethyl phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(2-aminomethyl phenyl) methyl]-5-methoxycarbonyl-1, and 2-dihydro carbazole-4 (3H)-ketone (1.2g, 3.5mM) with 2,3-two chloro-5,6-dicyano-1, (800mg, 3.6mM) solution that forms in 70ml toluene stirred 5 hours down at 80-90 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 260mg (22%) 9-[(2-aminomethyl phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1H NMR (DMSO-d6) δ 10.25 (s, 1H), 7.5 (d, 1H, J=8 Hz), 7.4 (t, 1H, J=8Hz), 7.3-7.1 (m, 4H), 6.9 (m, 2H), 6.6 (d, 1H, J=8 Hz), 6.1 (d, 1H, J=8 Hz), 5.65 (s, 2H), 3.8 (s, 3H), and 2.5 (s, 3H) .IR (KBr, cm
-1) 3200,1672,1440,1426,1332,1302,1265,1216,1141,761,749, and 718.MS (ES) m/e 344,346.C
22H
19NO
3Ultimate analysis:
Calculated value: C76.52; H5.51; N4.06
Measured value: C76.44; H5.66; N3.94C, 9-[(2-aminomethyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(2-aminomethyl phenyl) methyl]-(260mg, 0.75mM) solution in 10ml THF and the dense ammonium hydroxide water of 30ml carried out sonication 5 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to PH be 1.With ethyl acetate extraction water layer three times, and organic extracting solution water after will merging and saturated brine washing, use dried over mgso, filter and concentrated.Resistates is passed through column chromatography purifying (using the hexane/ethyl acetate gradient elution) on silica gel, obtains 90mg (36%) 9-[(2-aminomethyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole tawny solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.7 (m, 1H), 7.5 (m, 2H), 7.3 (m, 2H), (7.1 t, 1H, J=8 Hz), 6.95 (d, 1H, J=8 Hz), 6.85 (t, 1H, J=8Hz), 6.6 (d, 1H, J=8 Hz), 5.95 (d, 1H, J=8 Hz), 5.7 (s, 2H), and 2.5 (s, 3H) .IR (KBr, cm
-1) 3451,3191,1627,1600,1584,1562,1435,1329,1322,1263, and 774.MS (ES) m/e329,331.C
21H
18N
2O
2Ultimate analysis:
Calculated value: C76.36; H5.45; N8.48
Measured value: C75.66; H5.79; N8.07D, the 9-[(2-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.45ml 0.99mM) adds the 9-[(2-aminomethyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole (80mg, 0.24mM) solution that in 8ml DMF, forms.After 3 minutes, (115mg 0.72mM), and at room temperature stirred the mixture that generates 48 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate, and dried over mgso is used in water, 1N HCl, water and saturated brine washing, filters and concentrates.With resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 80mg (82%) the 9-[(2-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (DMSO-d6) δ 7.56 (br s, 1H), 7.5-7.1 (m, 9H), 6.9 (t, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 5.65 (s, 2H), 4.9 (s, 2H), 3.8 (s, 3H), and 2.5 (s, 3H) .IR (KBr, cm
-1) 3367,3153,1760,1740,1672,1644,1619,1591,1578,1498,1456,1425,1327,1200,1153,1109,1100, and 777.MS (FD) m/e 402.C
24H
22N
2O
4Ultimate analysis:
Calculated value: C71.64; H5.47; N6.96
Measured value: C71.51; H5.56; N6.67E, the 9-[(2-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will the 9-[(2-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (15.5mg, 0.039mM) and the suspension stirring that in 5ml ethanol, forms of 0.04ml (0.04mM) 1N sodium hydroxide 24 hours.Gather up the white precipitate of generation by filtration, it washed with small amount of ethanol, dry under vacuum condition then, obtain 10mg (63%) the 9-[(2-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H NMR (DMSO-d6) δ 7.55 (br s, 1H), 7.5-7.0 (m, 7H), 6.9 (d, 1H, J=8 Hz), 6.85 (t, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.2 (d, 1H, J=8 Hz), 5.6 (s, 2H), 4.35 (s, 2H), and 2.5 (s, 3H) .IR (KBr, cm
-1) 3390,1656,1613,1595,1573,1498,1455,1408,1325,1332, and 719.MS (ES) m/e387,389.C
23H
19N
2O
4Ultimate analysis:
Calculated value: C67.32; H4.63; N6.83
Measured value: C64.72; H4.44; N6.40 embodiment 36{9-[(3-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 9-[(3-aminomethyl phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (870mg, 3.58mM), between the a-bromo--dimethylbenzene (662mg, 3.58mM) and salt of wormwood (500mg, the suspension that 3.61mM) forms in 20ml DMF stirred 16 hours.Mixture is diluted with ethyl acetate, and anhydrous magnesium sulfate drying is used in water and saturated brine washing, filters and concentrates, and obtains 1.18g (95%) 9-[(3-aminomethyl phenyl) methyl]-5-methoxycarbonyl-1, the dark-coloured oily matter of 2-dihydro carbazole-4 (3H)-ketone.
1H NMR (DMSO-d6) δ 7.65 (dd, 1H, J=1 and 8 Hz), and 7.3-7.1 (m, 3H), (7.05 d, 1H, J=8 Hz), 7.0 (s, 1H), 6.85 (d, 1H, J=8 Hz), 5.5 (s, 2H), 3.8 (s, 3H), 3.0 (m, 2H), 2.45 (m, 2H), 2.3 (s, 3H), and 2.1 (m, 2H) .IR (CHCl
3, cm
-1) 300,2953,1724,1652,1605,1465,1442,1288,1174, and 1119.MS (ES) m/e 348.5.C
22H
21NO
3Ultimate analysis:
Calculated value: C76.08; H6.05; N4.03
Measured value: C74.53; H6.03; N3.68B, 9-[(3-aminomethyl phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(3-aminomethyl phenyl) methyl]-5-methoxycarbonyl-1, and 2-dihydro carbazole-4 (3H)-ketone (1.18g, 3.4mM) with 2,3-two chloro-5,6-dicyano-1, (800mg, 3.6mM) solution that forms in 70ml toluene stirred 6 hours down at 80-90 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 300mg (26%) 9-[(3-aminomethyl phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1H NMR (DMSO-d6) δ 10.2 (s, 1H), 7.65 (d, 1H, J=8 Hz), 7.35 (t, 1H, J=8Hz), 7.25 (t, 1H, J=8 Hz), 7.2-7.0 (m, 4H), 6.9 (m, 2H), 6.6 (d, 1H, J=8 Hz), 5.6 (s, 2H), 3.85 (s, 3H), and 2.2 (s, 3H) .IR (KBr, cm
-1) 3200,1673,1596,1440,1426,1394,1265,1216,1152,750,711, and 694.MS (ES) m/e 344,346.C
22H
19NO
3Ultimate analysis:
Calculated value: C76.52; H5.51; N4.06
Measured value: C76.22; H5.55; N3.97C, 9-[(3-aminomethyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(3-aminomethyl phenyl) methyl]-(300mg, 0.87mM) solution in 10ml THF and the dense ammonium hydroxide water of 30ml carried out sonication 5 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer three times, and organic extracting solution water after will merging and saturated brine washing, use dried over mgso, filter and concentrated.Resistates is passed through column chromatography purifying (using the hexane/ethyl acetate gradient elution) on silica gel, obtains 114mg (40%) 9-[(3-aminomethyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole pale solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (brs, 1H), 8.4 (br s, 1H), 7.8 (dd, 1H, J=1 and 8 Hz), 7.4 (m, 2H), 7.3 (t, 1H, J=8 Hz), 7.15-7.0 (m, 3H), 6.85 (d, 1H, J=8Hz), 6.6 (d, 1H, J=8 Hz), 5.95 (d, 1H, J=8 Hz), 5.65 (s, 2H), and 2.25 (s, 3H) .IR (KBr, cm
-1) 3434,3203,1629,1599,1579,1552,1443,1330,1262,1214, and 776.MS (ES) m/e 329,331.C
21H
18N
2O
2Ultimate analysis:
Calculated value: C76.36; H5.45; N8.48
Measured value: C77.56; H5.67; N8.26D, the 9-[(3-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.45ml 0.99mM) adds the 9-[(3-aminomethyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole (100mg, 0.30mM) solution that in 8ml DMF, forms.After 3 minutes, (O.72mM) 115mg, and at room temperature stirred the mixture that generates 24 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate, and dried over mgso is used in water and saturated brine washing, filters and concentrates.With resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 80mg (66%) the 9-[(3-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (DMSO-d6) δ 7.6 (d, 1H, J=8 Hz), 7.55 (br s, 1H), 7.45-7.0 (m, 8H), 6.9 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 5.65 (s, 2H), 4.9 (s, 2H), 3.75 (s, 3H), and 2.2 (s, 3H) .IR (KBr, cm
-1) 3367,3157,1760,1642,1589,1499,1455,1424,1328,1216,1151,1102,772, and 714.MS (FD) m/e 402.C
24H
22N
2O
4Ultimate analysis:
Calculated value: C71.64; H5.47; N6.96
Measured value: C71.01; H5.60; N6.66E, the 9-[(3-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will the 9-[(3-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (15.8mg, 0.039mM) and the suspension stirring that in 5ml ethanol, forms of 0.04ml (0.04mM) 1N sodium hydroxide 24 hours.Gather up the white precipitate of generation by filtration, it washed with small amount of ethanol, dry under vacuum condition then, obtain 10mg (62%) the 9-[(3-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H NMR (DMSO-d6) δ 7.55 (d, 1H, J=8 Hz), 7.5-7.0 (m, 9H), 6.85 (d, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), 5.6 (s, 2H), 4.35 (s, 2H), and 2.2 (s, 3H) .IR (KBr, cm
-1) 3390,1656,1613,1595,1573,1498,1455,1408,1325,1332, and 719.MS (ES) m/e387,389.C
23H
19N
2O
4The Na ultimate analysis:
Calculated value: C67.32; H4.63; N6.83
Measured value: C61.20; H4.64; N6.06 embodiment 37{9-[(3,5-3,5-dimethylphenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 9-[(3, the 5-3,5-dimethylphenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (850mg, 3.5mM), 3,5-dimethyl benzyl bromine (765mg, 3.8mM) and salt of wormwood (500mg, the suspension that 3.61mM) forms in 25ml DMF stirred 19 hours.Mixture is diluted with ethyl acetate, and anhydrous magnesium sulfate drying is used in water and saturated brine washing, filters and concentrates.Resistates is passed through column chromatography purifying (using eluent ethyl acetate) on silica gel, obtains 0.84g (67%) 9-[(3, the 5-3,5-dimethylphenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone foam.
1HNMR (DMSO-d6) δ 7.7 (dd, 1H, J=1 and 8 Hz), 7.3-7.2 (m, 2H), 6.9 (s, 1H), 6.75 (s, 2H), 5.45 (s, 2H), 3.8 (s, 3H), 3.0 (m, 2H), 2.45 (m, 2H), 2.2 (s, 6H), and 2.1 (m, 2H) .IR (KBr, cm
-1) 1726,1653,1602,1465,1442,1282,1172, and1116.MS (ES) m/e 362.C
23H
23NO
3Ultimate analysis:
Calculated value: C76.45; H6.37; N3.88
Measured value: C76.82; H6.54; N3.91B, 9-[(3, the 5-3,5-dimethylphenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With 9-[(3, the 5-3,5-dimethylphenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone (0.8g, 2.2mM) and 2,3-two chloro-5,6-dicyano-1, (550mg, 2.43mM) solution that forms in 70ml toluene stirred 5 hours between 80-90 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 234mg (29%) 9-[(3, the 5-3,5-dimethylphenyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1HNMR (DMSO-d6) δ 10.2 (s, 1H), 7.65 (d, 1H, J=8 Hz), 7.35 (t, 1H, J=8 Hz), 7.25 (t, 1H, J=8 Hz), (7.15 d, 1H, J=8 Hz), 7.05 (d, 1H, J=8 Hz), 6.9 (s, 1H), 6.7 (s, 2H), (6.6 d, 1H, J=8 Hz), 5.6 (s, 2H), 3.85 (s, 3H), and 2.2 (s, 6H) .IR (KBr, cm
-1) 3016,1675,1598,1441,1426,1394,1288,1270,1221,1152,754, and 713.MS (ES) m/e 358,360.C
23H
21NO
3Ultimate analysis:
Calculated value: C76.88; H5.85; N3.90
Measured value: C76.94; H6.00; N3.93C, 9-[(3, the 5-3,5-dimethylphenyl) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with 9-[(3, the 5-3,5-dimethylphenyl) methyl]-(200mg, 0.55mM) solution in 10ml THF and the dense ammonium hydroxide water of 30ml carried out sonication 4 days to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 2.5.With ethyl acetate extraction water layer three times, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (using the hexane/ethyl acetate gradient elution) on silica gel, obtains 90mg (47%) 9-[(3, the 5-3,5-dimethylphenyl) methyl]-4-hydroxyl-5-formamyl carbazole pale solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.6 (s, 1H), 8.4 (s, 1H), 7.75 (d, 1H, J=8 Hz), 7.45 (m, 2H), 7.3 (t, 1H, J=8 Hz), 7.1 (d, 1H, J=8 Hz), 6.85 (s, 1H), 6.7 (s, 2H), 6.6 (d, 1H, J=8 Hz), 5.6 (s, 2H), and 2.2 (s, 6H) .IR (KBr, cm
-1) 3417,3198,3113,3063,1631,1601,1562,1438,1332,1263,1217,781, and 773.MS (ES) m/e 343,345.C
22H
20N
2O
2Ultimate analysis:
Calculated value: C76.74; H5.81; N8.14
Measured value: C76.97; H5.94, N7.95D, 9-[(3,5-3,5-dimethylphenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.13ml 0.28mM) adds 9-[(3,5-3,5-dimethylphenyl) methyl]-4-hydroxyl-5-formamyl carbazole (80mg, 0.23mM) solution that in 8ml DMF, forms.After 3 minutes, (43mg 0.28mM), and at room temperature stirred the mixture that generates 17 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate, and dried over mgso is used in water and saturated brine washing, filters and concentrates.With resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 70mg (72%) 9-[(3,5-3,5-dimethylphenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (DMSO-d6) δ 7.6 (d, 1H, J=8 Hz), 7.55 (br s, 1H), 7.45-7.3 (m, 2H), 7.25 (d, 1H, J=8 Hz), 7.2 (br s, 1H), 7.1 (d, 1H, J=8 Hz), 6.9 (s, 1H), 6.8 (s, 2H), 6.6 (d, 1H, J=8 Hz), 5.65 (s, 2H), 4.9 (s, 2H), 3.75 (s, 3H), and 2.2 (s, 6H) .IR (KBr, cm
-1) 3362,3173,1758,1638,1583,1500,1454,1434,1330,1215,1151,1106,772,715, and 706.MS (ED) m/e 417.C
25H
24N
2O
4Ultimate analysis:
Calculated value: C72.12; H5.76; N6.73
Measured value: C71.80; H5.60; N6.73E, 9-[(3,5-3,5-dimethylphenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will 9-[(3,5-3,5-dimethylphenyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (18mg, 0.043mM) and the suspension stirring that in 5ml ethanol, forms of 0.043ml (0.043mM) 1N sodium hydroxide 42 hours.Gather up the white precipitate of generation by filtration, it washed with small amount of ethanol, dry under vacuum condition then, obtain 12mg (67%) 9-[(3,5-3,5-dimethylphenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H NMR (DMSO-d6) δ 7.6 (d, 1H, J=8 Hz), 7.5-7.3 (m, 4H), 7.1 (m, 2H), 6.9 (s, 1H), 6.8 (s, 2H), 6.6 (d, 1H, J=8 Hz), 5.65 (s, 2H), 4.35 (s, 2H), and 2.2 (s, 6H) .IR (KBr, cm
-1) 3385,1663,1616,1575,1498,1456,1412, and1330.MS (ES) m/e 401,403.C
24H
21N
2O
4The Na ultimate analysis:
Calculated value: C67.92; H4.95; N6.60
Measured value: C66.53; H5.06; N6.37 embodiment 38{9-[(3-iodophenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 9-[(3-iodophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (680mg, 3.5mM), the 3-iodobenzyl bromide (1.2g, 4.7mM) and salt of wormwood (500mg, the suspension that 3.61mM) forms in 20ml DMF stirred 18 hours.Mixture is diluted with ethyl acetate, and anhydrous magnesium sulfate drying is used in water and saturated brine washing, filters and concentrates.Resistates with methylene dichloride-ether development purifying, is obtained 0.70g (55%) 9-[(3-sulfophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone white solid.
1H NMR (DMSO-d6) δ 7.7-7.6 (m, 3H), 7.2 (m, 2H), 7.1 (t, 1H, J=8 Hz), 6.95 (d, 1H, J=8 Hz), 5.6 (s, 2H), 3.8 (s, 3H), 3.0 (t, 2H, J=6 Hz), 2.5 (t, 2H, J=6 Hz), and 2.2 (m, 2H) .IR (KBr, cm
-1) 1732,1639,1441,1421,1273,1117, and 763.MS (ES) m/e458,460.C
21H
18NO
3The I ultimate analysis:
Calculated value: C54.90; H3.92; N3.05
Measured value: C54.92; H3.98; N2.97B, 9-[(3-iodophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(3-iodophenyl) methyl]-5-methoxycarbonyl-1, and 2-dihydro carbazole-4 (3H)-ketone (700mg, 1.52mM) with 2,3-two chloro-5,6-dicyano-1, (380mg, 1.67mM) solution that forms in 70ml toluene stirred 5 hours between 70-80 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 220mg (31%) 9-[(3-iodophenyl) methyl]-the yellow foam of 4-hydroxy-5-methyl ester group carbazole.
1H NMR (DMSO-d6) δ 10.25 (s, 1H), 7.7 (d, 1H, J=8 Hz), 7.6 (m, 2H), 7.4 (t, 1H, J=8 Hz), (7.25 t, 1H, J=8 Hz), 7.2 (d, 1H, J=8 Hz), 7.1 (m, 3H), 6.65 (d, 1H, J=8Hz), 5.65 (s, 2H), and 3.8 (s, 3H) .IR (KBr, cm
-1) 3377 (br), 3028,1711,1672,1621,1580,1565,1495,1459,1439,1423,1332,1287,1267,1135,773,752,712, and 688.MS (ES) m/e 456,458.C
21H
16NO
3The I ultimate analysis:
Calculated value: C55.14; H3.50; N3.06
Measured value: C56.18; H3.87; N3.32C, 9-[(3-iodophenyl) methyl]-4-hydroxyl-5-formamyl carbazole
At room temperature, with the 9-[(3-iodophenyl) methyl]-(170mg, 0.37mM) the solution vigorous stirring in 10mlTHF and the dense ammonium hydroxide water of 30ml is 120 hours for 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 2.With ethyl acetate extraction water layer secondary, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (with ethylene dichloride/ethyl acetate gradient elution) on silica gel, obtains 61mg (37%) 9-[(3-iodophenyl) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (brs, 1H), 8.4 (br s, 1H), 7.8 (dd, 1H, J=1 and 8 Hz), 7.6-7.4 (m, 4H), 7.3 (t, 1H, J=8 Hz), 7.1-6.9 (m, 3H), 6.6 (d, 1H, J=8 Hz), and 5.7 (s, 2H) .IR (CHCl
3, cm
-1) 3423,3201 (br), 1630,1600,1579,1564,1445,1330,1261, and 775.MS (ES) m/e 441,443.C
20H
15N
2O
2The I ultimate analysis:
Calculated value: C54.30; H3.39; N6.33
Measured value: C54.92; H3.81; N6.08D, the 9-[(3-iodophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.07ml 0.15mM) adds the 9-[(3-iodophenyl) methyl]-4-hydroxyl-5-formamyl carbazole (60mg, 0.13mM) solution that in 8ml DMF, forms.After 3 minutes, (30mg 0.19mM), and at room temperature stirred the mixture that generates 17 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate, and dried over mgso is used in water and saturated brine washing, filters and concentrates.With resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 60mg (86%) the 9-[(3-iodophenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (DMSO-d6) δ 7.6-7.0 (m, 11H), 6.6 (d, 1H, J=8 Hz), 5.7 (s, 2H), 4.9 (s, 2H), and3.75 (s, 3H) .IR (KBr, cm
-1) 3500,3350,1727,1642,1291,1236, and 772.MS (ES) m/e 515.C
23H
19N
2O
4The I ultimate analysis:
Calculated value: C53.70; H3.70; N5.45
Measured value: C53.92; H3.72; N5.32E, the 9-[(3-iodophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will the 9-[(3-iodophenyl) methyl]-5-formamyl carbazole-4-yl } (15mg 0.03M) and the suspension stirring that forms in 5ml ethanol of 0.03ml (0.03mM) 1N sodium hydroxide 43 hours, then cools off in ice bath the ethoxyacetic acid methyl esters.Gather up the white precipitate of generation by filtration, it washed with small amount of ethanol, dry under vacuum condition then, obtain 6.5mg (43%) the 9-[(3-iodophenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H NMR (DMSO-d6) δ 7.6-7.0 (m, 11H), 6.6 (d, 1H, J=8 Hz), 5.7 (s, 2H), and 4.35 (s, 2H) .IR (KBr, cm
-1) 3456,3416,3335,1735,1638,1617,1580,1499,1452,1431,1431,1329,1255,1157,772,764, and 717.MS (ES) m/e 407,409,411.C
22H
16N
2O
4The INa ultimate analysis:
Calculated value: C50.57; H3.07; N5.36
Measured value: C49.57; H2.93; N5.06 embodiment 39{9-[(2-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid
A, 9-[(2-chloro-phenyl-) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
Under 25 ℃, 40% methyl alcohol is closed Triton B, and (2.42ml 5.3mM) slowly splashes into 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (873.7mg, 3.59mM) solution in 10ml DMF.After 5 minutes, (1.11g 5.39mM), and at room temperature stirred the mixture that generates 72 hours to add 2-chlorine bromotoluene.Mixture is diluted with ethyl acetate, wash with water five times, with the saturated brine washing once, use anhydrous magnesium sulfate drying, filter and concentrate.Again resistates is carried out purifying by crystallization from ethyl acetate, obtains 706.3mg (53%) 9-[(2-chloro-phenyl-) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone yellow solid.
1H NMR (DMSO-d6) δ 7.6 (m, 2H), 7.4-7.1 (m, 4H), 6.5 (d, 1H, J=8 Hz), 5.6 (s, 2H), 3.8 (s, 3H), 2.9 (t, 2H, J=6 Hz), 2.4 (t, 2H, J=6Hz), and 2.1 (m, 2H) .IR (CHCl
3, cm
-1) 3050,2950,1725,1655,1462,1446,1435,1288 and 1120.MS (ES) m/e 368,370.C
21H
18NO
3The Cl ultimate analysis:
Calculated value: C68.57; H4.93; N3.81
Measured value: C68.52; H5.18; N3.67B, 9-[(2-chloro-phenyl-) methyl]-4-hydroxy-5-methyl ester group carbazole
With the 9-[(2-chloro-phenyl-) methyl]-5-methoxycarbonyl-1, and 2-dihydro carbazole-4 (3H)-ketone (692.2mg, 1.88mM) with 2,3-two chloro-5,6-dicyano-1, (529mg, 2.32mM) solution that forms in 35ml toluene stirred 6 hours between 70-80 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 245mg (35%) 9-[(2-chloro-phenyl-) methyl]-the greeny solid of 4-hydroxy-5-methyl ester group carbazole.
1H NMR (DMSO-d6) δ 10.3 (s, 1H), 7.6 (t, 2H, J=8 Hz), 7.4 (t, 1H, J=8 Hz), 7.3-7.1 (m, 4H), 6.9 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), (6.3 d, 1H, J=8 Hz), 5.65 (s, 2H), and 3.85 (s, 3H) .IR (CHCl
3, cm
-1) 3200 (br), 1686,1598,1442,1428,1332,1285,1267, and 1141.MS (ES) m/e364,366,368.C
21H
16NO
3The Cl ultimate analysis:
Calculated value: C68.95; H4.41; N3.83
Measured value: C67.88; H4.29; N3.67C, 9-[(2-chloro-phenyl-) methyl]-4-hydroxyl-5-formamyl carbazole
Under 40-50 ℃, with the 9-[(2-chloro-phenyl-) methyl]-(238mg, 0.43mM) solution in 20ml THF and the dense ammonium hydroxide water of 25ml carried out sonication 20 hours to 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer secondary, and the organic extracting solution after will merging washs with saturated brine, uses dried over mgso, filters and concentrates.Resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate gradient elution) on silica gel, obtains 86.9mg (38%) 9-[(2-chloro-phenyl-) methyl]-4-hydroxyl-5-formamyl carbazole white solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.7 (m, 1H), 7.55 (d, 1H, J=8 Hz), 7.45 (m, 2H), 7.3 (m, 2H), (7.15 t, 1H, J=8 Hz), 6.95 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.2 (d, 1H, J=8 Hz), 5.75 (s, 2H) .IR (CHCl
3, cm
-1) 3500,3400,3200 (br), 1649,1597,1585,1446,1431,1331, and 1269.MS (ES) m/e 349,351,353.C
20H
15N
2O
2The Cl ultimate analysis:
Calculated value: C68.48; H4.31; N7.99
Measured value: C68.05; H4.33; N7.19D, the 9-[(2-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester
Under the room temperature, 40% methyl alcohol is closed Triton B (0.15ml 0.34mM) adds the 9-[(2-chloro-phenyl-) methyl]-4-hydroxyl-5-nitrogen base formyl radical carbazole (80mg, 0.23mM) solution that in 5ml DMF, forms.After 3 minutes, (182mg 0.91mM), and at room temperature stirred the mixture that generates 72 hours to add the monobromo-acetic acid tert-butyl ester.Mixture is diluted with ethyl acetate, and dried over mgso is used in water and saturated brine washing five times, filters and concentrates.With resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 57mg (53%) the 9-[(2-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid tert-butyl ester white solid.
1HNMR (DMSO-d6) δ 7.6 (d, 1H, J=8 Hz), 7.5-6.9 (m, 9H), 6.55 (d, 1H, J=8 Hz), 6.35 (d, 1H, J=8 Hz), 5.7 (s, 2H), 4.75 (s, 2H), and 1.45 (s, 9H) .IR (KBr, cm
-1) 1753 and 1678.MS (FD) m/e 464.C
26H
25N
2O
4The Cl ultimate analysis:
Calculated value: C67.17; H5.42; N6.03
Measured value; C64.02; H5.33; N5.77E, the 9-[(2-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid
At room temperature, incite somebody to action the 9-[(2-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester (46mg, the solution stirring that 0.1mM) in the 3ml trifluoroacetic acid, forms 2 hours.Under vacuum condition, remove and desolvate, resistates is developed with ether/hexane, dry under vacuum condition then, obtain 40mg (98%) the 9-[(2-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid white powder.
1H NMR (DMSO-d6) δ 12.9 (br s, 1H), 7.55 (s, 1H), 7.5 (d, 1H, J=8 Hz), 7.45 (s, 1H), 7.4-7.3 (m, 3H), 7.25 (t, 1H, J=8 Hz), 7.1-7.0 (m, 3H), 6.6 (d, 1H, J=8 Hz), (6.3 d, 1H, J=8 Hz), 5.7 (s, 2H), and4.8 (s, 2H) .IR (KBr, cm
-1) 3430,1735, and 1635.MS (ES) m/e 407,409.C
22H
17N
2O
4The Cl ultimate analysis:
Calculated value: C64.63; H4.19; N6.85
Measured value: C64.60; H4.08; N6.70 embodiment 40{9-[(2,3-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 9-[(2, the 3-difluorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (973mg, 4.0mM), a-bromo-2, the 3-difluoro toluene (1.01g, 4.8mM) and salt of wormwood (553mg, the suspension that 4.0mM) forms in 10ml DMF stirred 73 hours.Mixture is diluted with ethyl acetate, and anhydrous magnesium sulfate drying is used in water, 1N HCl, water, saturated sodium bicarbonate, water and saturated brine washing, filters and concentrates.Resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate wash-out) on silica gel, obtains 1.04g (70%) 9-[(2, the 3-difluorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone tawny solid.
1H NMR (CDCl
3) δ 7.4 (d, 1H, J=8 Hz), 7.35 (d, 1H, J=8 Hz), 7.15-6.9 (m, 5H), (6.35 t, 1H, J=8 Hz), 5.4 (s, 2H), 4.05 (s, 3H), 2.9 (t, 2H, J=6 Hz), 2.6 (t, 2H, J=6 Hz), and 2.25 (m, 2H) .IR (KBr, cm
-1) 1719 and 1650.MS (ES) m/e 368,370.C
21H
17NO
3F
2Ultimate analysis:
Calculated value: C68.29; H4.64; N3.79
Measured value: C68.50; H4.62; N3.94B, 9-[(2, the 3-difluorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With 9-[(2, the 3-difluorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone (490mg, 1.32mM) and 2,3-two chloro-5,6-dicyano-1, (336mg, 1.45mM) solution that forms in 70ml toluene stirred 2.25 hours down at 80-90 ℃ the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 165mg (34%) 9-[(2, the 3-difluorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1H NMR (CDCl
3) δ 10.25 (s, 1H), 8.0 (d, 1H, J=8 Hz), (7.6 d, 1H, J=8 Hz), and 7.5-7.4 (m, 2H), 7.05 (m, 1H), 6.9 (d, 1H, J=8 Hz), (6.85 d, 1H, J=8 Hz), 6.8 (m, 1H), (6.35 t, 1H, J=8 Hz), 5.6 (s, 2H), and 4.1 (s, 3H) .IR (KBr, cm
-1) 3025 and 1684.MS (ES) m/e 366,368.C
21H
15NO
3F
2Ultimate analysis:
Calculated value: C68.66; H4.12; N3.81
Measured value: C69.54; H4.44; N3.81C, 9-[(2, the 3-difluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole
At room temperature, with 9-[(2, the 3-difluorophenyl) methyl]-(514mg, 1.4mM) solution stirring in 5ml THF and the dense ammonium hydroxide water of 20ml is 94 hours for 4-hydroxy-5-methyl ester group carbazole.Mixture is diluted with ethyl acetate, and with 5N HCl it to be acidified to pH be 1.With ethyl acetate extraction water layer three times, and organic extracting solution water after will merging and saturated brine washing, use dried over mgso, filter and concentrated.Resistates is passed through column chromatography purifying (using the hexane/ethyl acetate gradient elution) on silica gel, obtains 320mg (65%) 9-[(2, the 3-difluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole yellow solid.
1H NMR (DMSO-d6) δ 10.45 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.8 (d, 1H, J=8 Hz), 7.5-7.2 (m, 4H), 7.05 (d, 1H, J=8 Hz), 6.95 (m, 1H), 6.6 (d, 1H, J=8Hz), 6.35 (t, 1H, J=8 Hz), and 5.9 (s, 2H) .IR (KBr, cm
-1) 3350,3125,1628,1598, and 1583.MS (ES) m/e 351,353.C
20H
14N
2O
2F
2Ultimate analysis:
Calculated value: C68.18; H4.01; N7.95
Measured value: C68.15; H4.23; N8.01D, 9-[(2,3-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.51ml 1.12mM) adds 9-[(2,3-difluorophenyl) methyl]-4-hydroxyl 5-formamyl carbazole (303mg, 0.86mM) solution that in 5ml DMF, forms.After 15 minutes, (270mg 1.72mM), and at room temperature stirred the mixture that generates 18 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate, and dried over mgso is used in water, 1N HCl, water and saturated brine washing, filters and concentrates.With resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 295mg (80%) 9-[(2,3-difluorophenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (CDCl
3) δ 7.5-7.3 (m, 5H), 7.05 (d, 1H, J=8 Hz), 6.8 (m, 1H), 6.6 (d, 1H, J=8 Hz), 6.4 (t, 1H, J=8 Hz), 6.2 (br.s, 1H), 6.0 (br s, 1H), 5.6 (s, 2H), 4.9 (s, 2H), and 3.8 (s, 3H) .IR (KBr, cm
-1) 3432,3180,1774,1766, and 1674.MS (ES) m/e 425.C
23H
18N
2O
4F
2Ultimate analysis:
Calculated value: C65.09; H4.28; N6.60
Measured value: C64.11; H4.12; N6.32E, 9-[(2,3-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will 9-[(2,3-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (85mg, 0.2mM) and the suspension stirring that in 5ml ethanol, forms of 0.22ml (0.22mM) 1N NaOH 18 hours.Add a small amount of ether/hexane, then but in refrigerator and cooled.Collect the white precipitate that generates by filtering; it is used small amount of ethanol/ethane/hexane wash; dry under vacuum condition then, obtain 77mg (89%) 9-[(2,3-difluorophenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H NMR (DMSO-d6) δ 7.7-7.2 (m, 6H), 7.2-7.0 (m, 3H), 6.6 (d, 1H, J=8 Hz), 6.45 (t, 1H, J=8 Hz), 5.7 (s, 2H), and 4.35 (s, 2H) .IR (KBr, cm
-1) 3467,3390,1662, and 1616.MS (ES) m/e 409,411,433.C
22H
15N
2O
4F
2The Na ultimate analysis:
Calculated value: C61.12; H3.50; N6.48
Measured value: C61.34; H3.38; N6.41 embodiment 41{9-[(2,6-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 9-[(2, the 6-difluorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (973mg, 4.0mM), a-bromo-2, the 6-difluoro toluene (1.01g, 4.8mM) and salt of wormwood (553mg, the suspension that 4.0mM) forms in 10ml DMF stirred 74 hours.Mixture is diluted with ethyl acetate, and anhydrous magnesium sulfate drying is used in water, 1N HCl, water, saturated sodium bicarbonate, water and saturated brine washing, filters and concentrates.Resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate wash-out) on silica gel, obtains 1.04g (70%) 9-[(2, the 6-difluorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone tawny solid.
1H NMR (CDCl
3) δ 7.5 (d, 1H, J=8 Hz), 7.35-7.2 (m, 3H), 6.95 (t, 2H, J=8 Hz), 5.4 (s, 2H), 4.0 (s, 3H), 3.05 (t, 2H, J=6 Hz), 2.6 (t, 2H, J=6 Hz), and 2.25 (m, 2H) .IR (KBr, cm
-1) 1728 and 1655.MS (ES) m/e 370.C
21H
17NO
3F
2Ultimate analysis:
Calculated value: C68.29; H4.64; N3.79
Measured value: C68.51; H4.82; N3.78B, 9-[(2, the 6-difluorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
Under the room temperature, will be dispersed in sodium hydride in the oil (257mg 6.42mM) adds 9-[(2,6-difluorophenyl) methyl with 60% concentration]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone (1.03g, 2.79mM) solution in the 7ml diox.After 5 minutes, (0.6ml 4.46mM), and at room temperature stirred mixture 1.75 hours to add the benzene sulfinic acid methyl esters.With mixture with the dilution of 10ml diox, add then Glacial acetic acid (0.37ml, 6.42mM).Again the mixture that generates was refluxed 45 minutes, be cooled to room temperature,, wash three times, use anhydrous magnesium sulfate drying, filter and concentrate with saturated sodium bicarbonate and saturated brine with the ethyl acetate dilution.Resistates is passed through column chromatography purifying (using the toluene wash-out) on silica gel, obtains 480mg (47%) 9-[(2, the 6-difluorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1HNMR (CDCl
3) δ 10.15 (s, 1H), 7.95 (d, 1H, J=8 Hz), 7.5 (d, 1H, J=8 Hz), 7.5-7.0 (m, 4H), 6.9-6.8 (m, 3H), 5.6 (s, 2H), and 4.1 (s, 3H) .IR (KBr, cm
-1) 3040 and 1682.MS (ES) m/e366,368.C
21H
15NO
3F
2Ultimate analysis:
Calculated value: C68.66; H4.12; N3.81
Measured value: C69.48; H4.07; N4.11C, 9-[(2, the 6-difluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole
At room temperature, with 9-[(2, the 6-difluorophenyl) methyl]-(514mg, 1.4mM) solution stirring in 5ml THF and the dense ammonium hydroxide water of 20ml is 64 hours for 4-hydroxy-5-methyl ester group carbazole.With 5N HCl pH is transferred to 10.5.Gather up the precipitation of generation by filtration, again it is suspended in the water, regulate pH to 11.7 with dense ammonium hydroxide.Collect the precipitation that generates by filtering once more; and precipitation is dissolved in ethyl acetate; wash three times with 5N sodium hydroxide, water and saturated brine; use anhydrous magnesium sulfate drying; filter and concentrate; obtain 310mg (70%) 9-[(2, the 6-difluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole yellow solid.
1H NMR (DMSO-d6) δ 10.4 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.8 (d, 1H, J=8 Hz), 7.6-7.0 (m, 7H), 6.6 (d, 1H, J=8 Hz), and 5.7 (s, 2H) .IR (KBr, cm
-1) 3404,3113,1626, and 1587.MS (ES) m/e351,353.C
20H
14N
2O
2F
2Ultimate analysis:
Calculated value: C68.18; H4.01; N7.95
Measured value: C68.45; H4.01; N7.87D, 9-[(2,6-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.49ml 1.07mM) adds 9-[(2,6-difluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole (290mg, 0.82mM) solution that in 5ml DMF, forms.After 15 minutes, (259mg 1.65mM), and at room temperature stirred the mixture that generates 24 hours to add the monobromo-acetic acid methyl esters.With the mixture dilute with water; and it is, it is developed with ether/hexane, and dry under vacuum condition by filtering the white precipitate of collecting generation; obtain 228mg (65%) 9-[(2,6-difluorophenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters white solid.
1H NMR (CDCl
3) δ 7.65 (d, 1H, J=8 Hz), 7.45-7.2 (m, 5H), 6.85 (t, 2H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), 6.3 (br s, 1H), 6.0 (br s, 1H), 5.5 (s, 2H), 4.9 (s, 2H), and3.8 (s, 3H) .IR (KBr, cm
-1) 3432,3170,1762, and 1675.MS (ES) m/e 425.C
23H
18N
2O
4F
2Ultimate analysis:
Calculated value: C65.09; H4.28:N6.60
Measured value: C65.05; H4.40:N6.53E, 9-[(2,6-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will 9-[(2,6-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (85mg, 0.2mM) and the suspension stirring that in 5ml ethanol, forms of 0.22ml (0.22mM) 1N NaOH 18 hours.Add a small amount of ether/hexane, then but in refrigerator and cooled.Collect the white precipitate that generates by filtering; it is washed with small amount of ethanol/ether/hexane; dry under vacuum condition then, obtain 82mg (95%) 9-[(2,6-difluorophenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H NMR (DMSO-d6) δ 7.6 (d, 1H, J=8 Hz), 7.55 (br s, 1H), 7.45-7.3 (m, 3H), 7.25 (t, 1H, J=8 Hz), 7.1-7.0 (m, 4H), 6.5 (d, 1H, J=8 Hz), 5.65 (s, 2H), and 4.3 (s, 2H) .IR (KBr, cm
-1) 3470,3360,1658, and 1606.MS (ES) m/e 409,411,433.C
22H
15N
2O
4F
2The Na ultimate analysis:
Calculated value: C61.12; H3.50; N6.48
Measured value: C59.18; H3.70; N6.19 embodiment 42{9-[(2,6-dichlorophenyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid sodium salt
A, 9-[(2, the 6-dichlorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
At room temperature, with 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (973mg, 4.0mM), a-bromo-2, the 6-toluene dichloride (1.19g, 4.8mM) and salt of wormwood (553mg, the suspension that 4.0mM) forms in 10ml DMF stirred 24 hours.Mixture is diluted with ethyl acetate, and anhydrous magnesium sulfate drying is used in water, 1N HCl, water, saturated sodium bicarbonate, water and saturated brine washing, filters and concentrates.Resistates is passed through column chromatography purifying (using the dichloromethane/ethyl acetate wash-out) on silica gel, obtains 900mg (56%) 9-[(2, the 6-dichlorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone white foam shape thing.
1H NMR (CDCl
3) δ 7.4-7.2 (m, 6H), 5.6 (s, 2H), 4.0 (s, 3H), 2.9 (t, 2H, J=6Hz), 2.55 (t, 2H, J=6 Hz), and 2.2 (m, 2H) .IR (KBr, cm
-1) 1725 and 1652.MS (ES) m/e 400,402,404.C
21H
17NO
3Cl
2Ultimate analysis:
Calculated value: C62.70; H4.26; N3.48
Measured value: C62.98; H4.35; N3.35B, 9-[(2, the 6-dichlorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With 9-[(2, the 6-dichlorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone (861mg, 2.14mM) and 2,3-two chloro-5,6-dicyano-1, (595mg, 2.57mM) solution that forms in 60ml toluene stirred 3.5 hours under reflux state the 4-benzoquinones.Mixture is passed through column chromatography direct purification (using the methylene dichloride wash-out) on silica gel, obtains 255mg (29%) 9-[(2, the 6-dichlorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole yellow solid.
1H NMR (CDCl
3) δ 10.05 (s, 1H), 7.95 (d, 1H, J=8 Hz), 7.6 (d, 1H, J=8 Hz), 7.45-7.2 (m, 5H), 6.95 (d, 1H, J=8 Hz), 6.8 (d, 1H, J=8 Hz), 5.75 (s, 2H), and 4.1 (s, 3H) .IR (KBr, cm
-1) 3430and 1668.MS (ES) m/e 409,411.C
21H
15NO
3Cl
2Ultimate analysis:
Calculated value: C63.02; H3.78; N3.50
Measured value: C63.78; H3.82; N3.59C, 9-[(2, the 6-dichlorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole
At room temperature, with 9-[(2, the 6-dichlorophenyl) methyl]-(240mg, 0.6mM) solution stirring in 5ml THF and the dense ammonium hydroxide water of 20ml is 22 hours for 4-hydroxy-5-methyl ester group carbazole.Collect the precipitation that generates by filtering, and dry under vacuum condition, obtain 151mg (65%) 9-[(2, the 6-dichlorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole yellow solid.
1H NMR (DMSO-d6) δ 10.35 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.7 (d, 1H, J=8 Hz), and 7.6-7.3 (m, 5H), 7.25 (t, 1H, J=8 Hz), 6.85 (d, 1H, J=8 Hz), 8.55 (d, 1H, J=8Hz), and 5.85 (s, 2H) .IR (KBr, cm
-1) 3429,1631, and 1597.MS (ES) m/e 385,387.C
20H
14N
2O
2Cl
2Ultimate analysis:
Calculated value: C62.35; H3.66; N7.27
Measured value: C62.87; H3.99; N6.00D, 9-[(2,6-dichlorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
Under the room temperature, 40% methyl alcohol is closed Triton B (0.23ml 0.49mM) adds 9-[(2,6-dichlorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole (146mg, 0.38mM) solution that in 5ml DMF, forms.After 15 minutes, (119mg 0.76mM), and at room temperature stirred the mixture that generates 17 hours to add the monobromo-acetic acid methyl esters.Mixture is diluted with ethyl acetate, and dried over mgso is used in water, 1N HCl, water, saturated sodium bicarbonate and saturated brine washing, filters and concentrates.With resistates on silica gel by column chromatography purifying (using eluent ethyl acetate), obtain 83mg (48%) 9-[(2,6-dichlorophenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters tawny solid.
1H NMR (DMSO-d6) δ 7.5-7.0 (m, 10H), 6.55 (d, 1H, J=8Hz), 5.8 (s, 2H), 4.9 (s, 2H), and 3.75 (s, 3H) .IR (KBr, cm
-1) .MS (ES) m/e 457,459.E, 9-[(2,6-dichlorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid sodium salt
Under 25 ℃, will 9-[(2,6-dichlorophenyl) methyl]-5-formamyl carbazole-4-yl } and the ethoxyacetic acid methyl esters (45.7mg, 0.1mM) and the suspension stirring that in 5ml ethanol, forms of 0.11ml (0.11mM) 1N NaOH 22 hours.Add a small amount of ether/hexane, then but in refrigerator and cooled.Collect the white precipitate that generates by filtering; it is washed with small amount of ethanol/ether/hexane; dry under vacuum condition then, obtain 40mg (86%) 9-[(2,6-dichlorophenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium salt white powder.
1H?NMR(DMSO-d6)δ7.6-7.4(m，6H)，7.3(t，1H，J＝8?Hz)，7.2(t，1H，J＝8?Hz)，7.0(d，1H，J＝8?Hz)，6.9(t，1H，J＝8?Hz)，6.5(d，1H，J＝8?Hz)，5.8(s，2H)，and?4.25(s，2H).MS(ES)m/e441，443，445.
Embodiment 43 preparation the 9-[(3-Trifluoromethoxyphen-l) methyl]-5-formamyl carbazole-4-yl } sodium salt of ethoxyacetic acid
A.9-[(3-methyl Trifluoromethoxyphen-l)]-5-methoxycarbonyl-1,2-dihydro carbazole-4-(3H)-ketone
At stirring at room 5-methoxycarbonyl-1, and 2-dihydro-9H-carbazole-4-(3H)-ketone (935mg, 3.85mM), 3-trifluoro-methoxybenzyl bromide (1.0g, 3.93mM) and salt of wormwood (531mg, the suspension of 20mlDMF 3.85mM) 17 hours.With ethyl acetate diluted mixture thing, anhydrous magnesium sulfate drying is used in water and saturated brine washing, and filtering and concentrating obtains the 9-[(3-Trifluoromethoxyphen-l of 1.6g (100%)) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4-(3H)-ketone is spumescence.Ultimate analysis: C
22H
18NO
4F
3: calculated value: C, 63.31; H, 4.32; N, 3.36 measured values: C, 63.12; H, 4.35; N, 3.31
1H NMR (DMSO-d6) δ 7.7 (dd, 1H, J=1 and 8 Hz), 7.45 (t, 1H, J=8 Hz), 7.3-7.1 (m, 4H), 7.05 (d, 1H, J=8 Hz), 5.6 (s, 2H), 3.8 (s, 3H), 3.0 (m, 2H), 2.45 (m, 2H), and 2.1 (m, 2H) .IR (CHCl
3, cm
-1) 1729,1647,1439,1259,1176, and 1116.MS (ES) m/e 418.B.9-[(3-Trifluoromethoxyphen-l) methyl]-4-hydroxy-5-methyl ester group carbazole
Reflux and stir the 9-[(3-Trifluoromethoxyphen-l) methyl-5-methoxycarbonyl-1,2-dihydro carbazole-4-(3H)-ketone (0.75g, 1.8mM) and 2,3-two chloro-5,6-dicyano-1,4-benzoquinones (490mg, 70ml toluene solution 2.16mM) 6 hours, obtain the 9-[(3-Trifluoromethoxyphen-l of 300mg (40%) by silica gel column chromatography purified mixture (using the methylene dichloride wash-out)) methyl]-4-hydroxy-5-methyl ester group carbazole, be yellow solid.
1H NMR (DMSO-d6) δ 10.25 (s, 1H), 7.7 (d, 1H, J=8 Hz), 7.5-7.0 (m, 8H), 6.6 (d, 1H, J=8Hz), 5.7 (s, 2H), and 3.85 (s, 3H) .IR (KBr, cm
-1) 3200,1673,1441,1268,1217,1173, and 753.MS (ES) m/e 414,416. ultimate analyses: C
22H
16NO
3F
3: calculated value: C, 63.61; H, 3.86; N, 3.37 measured values: C, 63.40; H, 3.99; N, the 3.43C.9-[(3-Trifluoromethoxyphen-l) methyl]-4-hydroxyl-5-formamyl carbazole
Vigorous stirring 9-[(3-Trifluoromethoxyphen-l) methyl]-(260mg, 0.62mM) solution in 10mlTHF and the dense ammonium hydroxide aqueous solution of 30ml is 132 hours, also with 5N HCl pH is transferred to 1 with ethyl acetate diluted mixture thing for 4-hydroxy-5-methyl ester group carbazole.With ethyl acetate extraction water layer 3 times, the organic extraction that water and saturated brine washing merge use dried over mgso, filters also concentrated.Obtain 150mg (60%) 9-[(3-Trifluoromethoxyphen-l by silica gel chromatography residue (using the hexane/ethyl acetate gradient elution)) methyl]-4-hydroxyl-5-formamyl carbazole, be gray solid.
1H NMR (DMSO-d6) δ 10.5 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.85 (dd, 1H, J=1and 8 Hz), 7.5-7.15 (m, 5H), 7.1 (d, 1H, J=8 Hz), (7.0 d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 5.95 (d, 1H, J=8 Hz) and 5.65 (s, 2H) .IR (KBr, cm
-1) 3431,3203,1629,1601,1580,1548,1446,1330,1261,1215, and 777.MS (ES) m/e 399,401. ultimate analyses: C
21H
15N
2O
2F
3: calculated value: C, 63.00; H, 3.75; N, 7.0 measured values: C, 63.15; H, 4.07; N, the 6.84D.{9-[(3-Trifluoromethoxyphen-l) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
At room temperature 40% methyl alcohol is closed Triton B (0.15ml; 0.34mM) be added to the 9-[(3-Trifluoromethoxyphen-l) methyl]-4-hydroxyl-5-formamyl carbazole (115mg; 0.28mM) 8mlDMF solution in; (65mg is 0.41mM) and in the mixture of stirring at room gained 23 hours to wherein adding the monobromo-acetic acid methyl esters after 3 minutes.With ethyl acetate diluted mixture thing, dried over mgso is used in water and saturated brine washing, filters and concentrates.By silica gel chromatography residue (using eluent ethyl acetate) obtain 112mg (83%) the 9-[(3-Trifluoromethoxyphen-l) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid methyl esters, be white solid.
1H NMR (DMSO-d6) δ 7.6 (d, 1H, J=8 Hz), 7.55 (br s, 1H), 7.5-7.0 (m, 9H), 6.6 (d, 1H, J=8 Hz), 5.7 (s, 2H), 4.9 (s, 2H), and 3.75 (s, 3H) .IR (KBr, cm
-1) 3488,3141,1763,1674,1501,1444,1269,1215,1178,1102,772, and 714.MS (FD) m/e 472. ultimate analyses: C
24H
19N
2O
5F
3: calculated value: C, 61.02; H, 4.03; N, 5.93 measured values: C, 61.05; H, 4.17; N, the 5.81E.{9-[(3-Trifluoromethoxyphen-l) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid sodium
25 ℃ of stirrings the 9-[(3-Trifluoromethoxyphen-l) methyl]-5-formamyl-4-yl the ethoxyacetic acid methyl esters (22.4mg, 0.047mM) and the 5ml alcoholic acid suspension of 0.065ml (0.065mM) 1N NaOH 24 hours.Solvent removed in vacuo also is suspended in residue in the ethanol; collect the white precipitate that obtains by filtering; with small amount of ethanol washing, then vacuum-drying obtain 9mg (41%) the 9-[(3-Trifluoromethoxyphen-l) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid sodium, be white powder.MS(ES)m/e457，459。
Embodiment 44{9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid
A.2-methoxycarbonyl-6-nitro-2 '-methoxyl biphenyl
With 2-chloro-3-nitrobenzoic acid methyl esters (2.16g, 10.0mM), 2-methoxyphenylboronic acid (1.64g, 10.5mM), (584mg, 0.5mM) (10.5ml, 50mlTHF solution 21.0mM) wrap in the aluminium foil and reflux and stirred 27 hours tetrakis triphenylphosphine palladium (0) with the 2M aqueous sodium carbonate.Vacuum remove THF and with residue be dissolved in the ethyl acetate, water, 1N hydrochloric acid, water, saturated sodium bicarbonate and saturated brine purging compound, use dried over mgso, filter also and concentrate.Light brown oily thing (using the toluene/ethyl acetate gradient elution) by the silica gel chromatography gained obtain 2.0g (69%) 2-methoxycarbonyl-6-nitro-2 '-methoxyl biphenyl, be the light orange solid.
1H NMR (CDCl
3) δ 8.05 (d, 1H, J=8 Hz), 7.95 (d, 1H, J=8 Hz), 7.55 (t, 1H, J=8 Hz), (7.35 t, 1H, J=8 Hz), 7.05 (d, 1H, J=8 Hz), 7.0 (t, 1H, J=8 Hz), 6.9 (d, 1H, J=8Hz), 3.7 (s, 3H), and 3.6 (s, 3H) .IR (KBr, cm
-1) 1730,1538,1499,1366,1298,1271,1130,774,765,759,752, and707.MS (ES) m/e 288. ultimate analyses: C
15H
13NO
5: calculated value: C, 62.72; H, 4.56; N, 4.88 measured values: C, 62.65; H, 4.61; N, 4.72B.9H-4-methoxyl group-5-methoxycarbonyl carbazole
In the test tube of sealing, in 150-160 ℃ of heating 2-methoxycarbonyl-6-nitro-2 '-(144mg, (2.0mM) solution is 4 hours for 339mg, 0.35ml, then room temperature 15 hours for triethyl-phosphite 0.5mM) for methoxyl biphenyl.With toluene vacuum-drying mixture, obtain 9H-4-methoxyl group-5-methoxycarbonyl carbazole of 39.0mg (30%) then by preparation TLC purifying (with 4: 1 toluene/ethyl acetate wash-outs) on silica gel, be brown solid.
1H NMR (CDCl
3) δ 8.25 (s, 1H), 7.4-7.2 (m, 4H), 7.05 (d, 1H, J=8 Hz), 6.65 (d, 1H, J=8 Hz), and 4.05 (s, 6H) .IR (CHCl
3, cm
-1) 3274 (br), 1706,1602,1583,1456,1431,1351,1333,1294,1239,1198,1175,1144,1103,781, and 724.MS (ES) m/e 256. ultimate analyses: C
15H
13NO
3: calculated value: C, 70.58; H, 5.13; N, 5.49 measured values: C, 70.85; H, 5.29; N, the 5.29C.9-[(2-xenyl) methyl]-4-methoxyl group-5-methoxycarbonyl carbazole
(727mg, 15mlDMF solution 2.85mM) are added in the mineral oil suspension (342mg, 8.56mM use twice of hexane wash) of 60%NaH with 9H-4-methoxyl group-5-methoxycarbonyl carbazole in room temperature.Gas produce stop after, (0.79ml is 4.19mM) and in stirring at room mixture 19 hours, with ethyl acetate and water diluted mixture thing to add 2-(brooethyl) biphenyl.Water, 1N hydrochloric acid, water, saturated sodium bicarbonate and saturated brine purging compound are used dried over mgso, filter and concentrate the 9-[(2-xenyl that obtains 1.2g (100%)) methyl]-4-methoxyl group-5-methoxycarbonyl carbazole, be yellow solid.
1H NMR (CDCl
3) δ 7.6-7.2 (m, 11H), 7.05 (t, 1H, J=8 Hz), 6.8 (d, 1H, J=8 Hz), 6.65 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 5.4 (s, 2H) and 4.0 (s, 6H) .IR (KBr, cm
-1) 1727.MS (ES) m/e 422. ultimate analyses: C
28H
23NO
3: calculated value: C, 79.79; H, 5.50; N, 3.32 measured values: C, 79.53; H, 5.61; N, the 3.15D.9-[(2-xenyl) methyl]-4-hydroxy-5-methyl ester group carbazole
(1.0M is in methylene dichloride with boron tribromide at-10 ℃, 1.69ml, 1.69mM) be added to the 9-[(2-xenyl lentamente) methyl]-4-methoxyl group-5-methoxycarbonyl carbazole (547mg, 1.3mM) the 5ml dichloromethane solution in, (1.31ml 32.5mM) ends mixture reaction and stirring at room 5 hours with methyl alcohol after 2 hours.With ethyl acetate diluted mixture thing.Water, 1N hydrochloric acid, water, saturated sodium bicarbonate and saturated brine purging compound are used dried over mgso, filter and concentrate.Obtain 445mg (84%) 9-[(2-xenyl by silica gel chromatography residue (using the methylene dichloride wash-out)) methyl]-4-hydroxy-5-methyl ester group carbazole, be yellow spumescence.
1H NMR (CDCl
3) δ 10.35 (s, 1H), 7.95 (d, 1H, J=8 Hz), 7.6-7.2 (m, 10fH), 7.05 (t, 1H, J=8 Hz), 6.8 (m, 2H), 6.6 (d, 1H, J=8 Hz), 5.4 (s, 2H), and 4.1 (s, 3H) .IR (KBr, cm
-1) 3200 (br), 1680,1596,1451,1439,1427,1333,1262,1217,1137,752,713,1763 and 703.MS (ES) m/e, 406,408. ultimate analyses: C
27H
21NO
3: calculated value: C, 79.59; H, 5.19; N, 3.44 measured values: C, 80.62; H, 5.73; N, the 3.44E.9-[(2-xenyl) methyl]-4-hydroxyl-5-formamyl carbazole
At 40-50 ℃ with the 9-[(2-xenyl) methyl]-(407.5mg, 1.0mM) the solution supersound process in 5mlTHF and the dense ammonium hydroxide aqueous solution of 20ml is 28.5 hours for 4-hydroxy-5-methyl ester group carbazole.Also PH is transferred to 1 with ethyl acetate diluted mixture thing with 5N HCl.With ethyl acetate extraction water layer 3 times, the organic extraction that water and saturated brine washing merge use dried over mgso, filters also concentrated.Obtain 165mg (42%) 9-[(2-xenyl by silica gel chromatography residue (using the dichloromethane/ethyl acetate gradient elution)) methyl]-4-hydroxyl-5-formamyl carbazole, be yellow solid.
1H NMR (DMSO-d6) δ 10.45 (s, 1H), 8.8 (br s, 1H), 8.4 (br s, 1H), 7.6-7.2 (m, 11H), (7.05 t, 1H, J=8 Hz), 6.75 (d, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), 6.35 (d, 1H, J=8 Hz), and 5.55 (s, 2H) .IR (KBr, cm
-1) 3451,3331, and 1639.MS (ES) m/e 391,393. ultimate analyses: C
26H
20N
2O
2: calculated value: C, 79.57; H, 5.14; N, 7.14 measured values: C, 79.60; H, 5.37; N, the 6.90F.{9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tertiary butyl ester
Under the room temperature 40% methyl alcohol closed Triton B (0.2ml; 0.44mM) be added to the 9-[(2-xenyl) methyl]-4-hydroxyl-5-formamyl carbazole (141mg; 0.36mM) 5mlDMF solution in; (107mg is 0.54mM) and in the mixture of stirring at room gained 6.5 hours to wherein adding tert-butylbromo acetate after 5 minutes.With ethyl acetate diluted mixture thing, water, 1N HCl, water, dried over mgso is used in saturated sodium bicarbonate and saturated brine washing, filters and concentrates.By silica gel chromatography residue (using the dichloromethane/ethyl acetate gradient elution) obtain 140mg (76%) the 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid tertiary butyl ester, be white foam.
1H NMR (CDCl
3) δ 7.6-7.2 (m, 13H), 7.05 (t, 1H, J=8 Hz), 6.85 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), 5.4 (s, 2H), 4.8 (s, 2H), and 1.45 (s, 9H) .IR. (CHCl
3, cm
-1) 1753and 1674.MS (ES) m/e 507. ultimate analyses: C
32H
30N
2O
4: calculated value: C, 75.87; H, 5.97; N, 5.53 measured values: C, 76.10; H, 6.12; N, the 5.37G.{9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid
Stirring at room the 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid tertiary butyl ester (116mg, 3ml trifluoroacetic acid solution 0.23mM) 2 hours, solvent removed in vacuo.Develop residue with ethyl acetate/hexane, then vacuum-drying obtain 103mg (100%) the 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid, be white powder.
1H NMR (DMSO-d6) δ 12.95 (br s, 1H), 7.75 (s, 1H), 7.65 (d, 2H, J=8 Hz), 7.55 (t, 2H, J=8 Hz), 7.4 (s, 1H), 7.35-7.2 (m, 6H), 7.05 (m, 2H), 6.9 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.4 (d, 1H, J=8 Hz), 5.55 (s, 2H), and4.8 (s, 2H) .IR (KBr, cm
-1) 3400,3200,1736,1636,1618,1583,1499,1455,1433,1329,1249,1155,753, and 713.MS (ES) m/e 449,451. ultimate analyses: C
28H
22N
2O
4: calculated value: C, 74.65; H, 4.92; N, 6.22 measured values: C, 75.47; H, 4.77; N, 6.24
Embodiment 45 will the 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid esterification be the 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid methyl esters
At room temperature stir the 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl } and ethoxyacetic acid (35mg, 0.08mM), methyl iodide (12mg, 0.09mM) and salt of wormwood (13mg, the suspension of 2mlDMF 0.09mM) 4.5 hours.With ethyl acetate diluted mixture thing.Water, saturated sodium bicarbonate, water and saturated brine purging compound are used dried over mgso, filter and concentrate obtain 36mg (100%) the 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid methyl esters, be white solid.
1H NMR (CDCl
3) δ 7.6-7.2 (m, 11H), 7.1 (t, 1H, J=8 Hz), 6.85 (d, 1H, J=8 Hz), 6.6 (d, 1H, J=8 Hz), 6.55 (d, 1H, J=8 Hz), 5.8 (br s, 2H), 5.4 (s, 2H), 4.8 (s, 2H), and 3.75 (s, 3H) .IR (KBr, cm
-1) 1750 and 1666.MS (ES) m/e, 465. ultimate analyses: C
29H
24N
2O
4: calculated value: C, 74.98; H, 5.21; N, 6.03 measured values: C, 75.09; H, 5.57; N, 5.63
Embodiment 46[9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] preparation of acetate
A.9-benzyl-4-carboxyl-5-methoxyl group-1,2,3,4-tetrahydro carbazole ethyl ester
Handle 1.50g (4.02mmol) 9-benzyl-4-carboxyl-8-chloro-5-methoxyl group-1 with 0.24g5%Pd-C, 2,3, the 25ml ethanolic soln of 4-tetrahydro carbazole ethyl ester and 0.45g (4.40mmol) triethylamine, and under 60 pounds of/square inch pressure the mixture 16 hours of hydrogenation gained, filter reaction mixture and vacuum concentration obtain the 1.40g brown solid.
1H NMR (CDCl
3) δ 7.30-7.19 (m, 3H), 7.03-6.95 (m3H), 6.80 (d, 1H, J=8.1 Hz), 6.44 (d, 1H, J=7.7 Hz), (5.22 d, 2H, J=5.9 Hz), 4.22-4.11 (m, 3H), 3.82 (s, 3H), 2.75-2.64 (m, 1H), and 2.59-2.48 (m, 1H), 2.11-1.64 (m, 4H), and 1.25 (t, 3H, J=7.0 Hz) .IR (CHCl
3) 2959,1725,1499,1453,1260,1178,1128cm
-1Ultimate analysis: C
23H
25NO
3: calculated value: 363.1836 measured values: 363.1834B.9-benzyl-4-formamyl-5-hydroxyl-1,2,3,4-tetrahydro carbazole
Use 22.40ml BBr down for 0 ℃
3(22.40mmol; The dichloromethane solution of 1M) handles 1.00g (2.80mmol) 9-benzyl-4-carboxyl-5-methoxyl group-1,2,3, the 15ml dichloromethane solution of 4-tetrahydro carbazole ethyl ester.Remove cooling bath and stirred reaction mixture and show starting raw material total overall reaction (1.5 hours) up to tlc analysis (10% ethyl acetate/hexane).Reaction is cooled to 0 ℃ also to be ended with 5.0ml methyl alcohol.Stir the mixture 18 hours and the vacuum concentration of gained under the room temperature.Be dissolved in the dark oil thing of gained in the 200ml methylene dichloride and water (100ml) and saturated sodium bicarbonate aqueous solution (100ml) wash the solution that obtains.Solvent removed in vacuo obtains the oily matter of 700mg black.Obtain 400mg 9-benzyl-4-carboxyl-5-hydroxyl-1,2,3 by circular chromatography purifying (10% ethyl acetate/hexane), 4-tetrahydro carbazole ethyl ester is directly used in next procedure with it.
Phenol is dissolved in the solution of also handling gained among the 40ml THF with 10ml ammonium hydroxide.Add a cover and stir tempestuously the mixture 13 days of gained to reaction vessel.Incline reaction mixture in water and usefulness ethyl acetate (3x150ml) extraction mixture.The dry organic layer (sodium sulfate) that merges filters and vacuum concentration obtains the brown foam of 300mg.By obtaining initial phenol of 50mg and 80mg (0.03mmol behind circular chromatography (3% ethanol/methylene) purifying; 22%) 9-benzyl-4-formamyl-5-hydroxyl-1,2,3, the 4-tetrahydro carbazole
1H NMR (CDCl
3) δ 7.33-7.24 (m, 3H), 7.06-6.97 (m, 3H), 6.81 (d, 1H, J=8.1 Hz), 6.56 (d, 1H, J=7.5 Hz), (5.22 d, 2H, J=2.2 Hz), and 4.20-4.15 (m, 1H), 2.78-2.67 (m, 1H), 2.63-2.51 (m, 1H), 2.35-2.27 (m, 1H), (m 3H), does not find phenol proton IR (CHCl3) 3007,1667 to and2.09-1.91,1586,1567,1496,1266cm-1; Ultimate analysis: C
20H
21N
2O
2: calculated value: 321.1603 measured values: 321.1607C.[9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] the ethoxyacetic acid methyl esters
With 61mg (0.30mmol) Cs
2CO
3, then handle 80mg (0.25mmol) 9-benzyl-4-formamyl-5-hydroxyl-1,2,3, the 2.5mlDMF solution of 4-tetrahydro carbazole with 26mg (0.30mmol) methyl bromoacetate.At room temperature stir the mixture and show that up to tlc all starting raw materials react finish (2 hours).Water (10ml) diluted reaction mixture also uses ethyl acetate (3x10ml) to extract, and the organic extraction that water (3x20ml) washing merges is used dried over sodium sulfate, filters also vacuum concentration.By circular chromatography purifying residue (SiO)
22.5% ethanol/methylene) obtains 50mg (0.13mmol, 51%) [9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid methyl esters, be oily matter.
1H NMR (CDCl
3) δ 7.33-7.21 (m, 3H), 7.05-6.98 (m, 3H), 6.98 (d, 1H, J=7.4Hz), 6.46 (br s, 1H), 6.37 (d, 1H, J=7.7 Hz), 5.52 (br s, 1H), 5.23 (d, 1H, J=4.9 Hz) 4.79-4.70 (m, 2H), 4.20-4.15 (m, 1H), 3.81 (s, 3H), 2.79-2.69 (m, 1H), 2.63-2.49 (m, 1H), 2.43-2.35 (m, 1H), and 2.25-2.09 (m, 1H), and 1.99-1.78 (m, 2H) .IR (CHCl
3, cm
-1) 1759,1670,1497,1453,1440, and 1132.MS (ES) m/e 393 (M+1). ultimate analysis: C
23H
24N
2O
4: calculated value: C, 70.39; H, 6.16; N, 7.14 measured values: C, 70.29; H, 6.31; N, 7.08D.[9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid
Handle 30mg (0.076mmol) [9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] the 1.0ml THF of ethoxyacetic acid methyl esters and the solution of 1.0ml methyl alcohol with the 0.2ml 1N LiOH aqueous solution (0.2mmol), stirred the mixture 18 hours.Add the other 0.2ml 1N LiOH aqueous solution (0.2mmol) and continue and stir.1 hour final vacuum enriched mixture.Residue is dissolved in the solution of also using 0.2N aqueous hydrochloric acid acidifying gained in the 2.0ml water.Cross filter solid and drying and obtain 25mg[9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid, be white solid.
1H NMR (DMSO-d6) δ 7.36-7.12 (m, 5H), 7.05-6.83 (m, 5H), 6.71 (br s, 1H), 6.35 (d, 1H, J=7.6 Hz), 5.27 (s, 2H), 4.64 (s, 2H), and 3.93-3.84 (m, 2H), 2.75-2.64 (m, 1H), 2.16-1.95 (m, 2H), and 1.81-1.64 (m, 2H) and a proton peak that between 2.58-2.40, is covered by the water peak
IR (KBr, cm
-1) 3435,2936,1722,1644,1586,1566,1495,1451,1354,1227,1134,730,716, and 698.MS (ES) m/e 377 (M-1) and 379 (M+1). ultimate analysis: C
22H
22N
2O
4: calculated value: C, 69.83; H, 5.86; N, 7.40 measured values: C, 70.11; H, 5.76; N, 7.12
Embodiment 47{9-[(2-pyridyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid
A.9-[(2-methyl pyridyl)]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
At 0 ℃ with 2-pyrmethyl chloride hydrochloride (1.10g, 6.70mmol) processing 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (1.50g, 6.17mmol), salt of wormwood (2.60g, 18.8mmol) and the suspension of the sodium iodide (about 10mg) of catalytic amount, remove cooling bath and stirring at room 72 hours.Ethyl acetate extraction mixture 4 times will also be used in the reaction mixture impouring water (100ml).Wash the organic extraction 4 times of merging with water and, use anhydrous sodium sulfate drying, filter and concentrate with saturated brine washing 1 time.(elder generation is with 70% by flash chromatography on silica gel method purifying residue, then 80%, 85% ethyl acetate/hexane wash-out then) obtain 1.70g (82%) 9-[(2-pyridyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone, be oily matter, can solidify after leaving standstill.
1H NMR (CDCl
3) δ 8.52 (br s, 1H), 7.54-7.47 (m, 1H), 7.34-7.26 (m, 2H), 7.18-7.11 (m, 2H), 6.67 (d, J=7.8Hz, 1H) 5.34 (s, 2H), 3.99 (s, 3H), 2.87 (t, 2H, J=6.0 Hz), 2.50 (t, 2H, J=6.3 Hz), and 2.20-2.13 (m, 2H) .IR (CHCl
3, cm
-1) 3010,2953,1725,1654,1463,1446,1288 and 1121.MS (ES) m/e, 335 (M+1). ultimate analysis: C
20H
18N
2O
3: calculated value: C, 71.84; H, 5.43; N, 8.38 measured values: C, 71.70; H, 5.49; N, the 8.37B.9-[(2-pyridyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With sodium hydride (140mg; 3.50mmol; The dispersion liquid of 60% mineral oil) handle the 9-[(2-pyridyl) methyl]-5-methoxycarbonyl-1, and 2-dihydro carbazole-4 (3H)-ketone (500mg, 2ml dioxane solution 1.50mmol), and stir the mixture 15 minutes of gained.To wherein being added dropwise to benzene sulfinic acid methyl esters (0.32ml; 2.45mmol) and at the stirring at room reaction mixture.0.5 begin to produce gas after hour, and reaction mixture becomes dark-brown.Stirred reaction mixture shows that up to tlc all starting raw materials all react finish (1 hour), at this moment add glacial acetic acid (0.20ml; 3.50mmol).Add other 2ml diox and be beneficial to stir, and heated mixt makes its gentle reflux 1 hour.Reaction mixture is also used ethyl acetate (50ml) dilution.Separate organic layer,, use anhydrous sodium sulfate drying, filter and concentrate with saturated sodium bicarbonate aqueous solution washing 1 time with saturated brine washing 1 time.Residue is obtained 470.0mg (94%) 9-[(2-pyridyl by cyclical chromatography purifying (with 20% ethyl acetate/hexane wash-out) on silica gel) methyl]-4-hydroxy-5-methyl ester group carbazole, be solid.
1H NMR (CDCl
3) δ 10.37 (s, 1H), 8.61 (d, 1H, J=3.7Hz), (8.01 d, 1H, J=7.8 Hz), 7.63 (d, 1H, J=8.3 Hz), and 7.47-7.39 (m, 3H), 7.19-7.14 (m, 1H), (6.94 d, 1H, J=8.3 Hz), 6.84 (d, 1H, J=8.3 Hz), 6.59 (d, 1H, J=7.8 Hz), 5.66 (s, 2H), and 4.10 (s, 3H) .IR (CHCl
3, cm
-1) 3200 (br), 1686,1597,1442,1428,1332,1286, and 1268.MS (ES) m/e 333 (M+1). ultimate analysis: C
20H
16N
2O
3: calculated value: C, 72.28; H, 4.85; N, 8.43 measured values: C, 72.44; H, 4.79; N, the 8.44C.9-[(2-pyridyl) methyl]-4-hydroxyl-5-formamyl carbazole
Handle the 9-[(2-pyridyl with the ammonia air-flow) methyl]-(480mg, the solution of 10mlTHF 1.43mmol) and the dense ammonium hydroxide aqueous solution of 40ml also makes it saturated to 4-hydroxy-5-methyl ester group carbazole.Add a cover and under agitation mixture heating up to 35 ℃ is shown starting raw material reaction finish (20 hours) up to tlc to reaction vessel.Evaporation THF also uses the saturated water layer of solid sodium chloride.Extract mixture 3 times with THF.With the organic extraction that anhydrous sodium sulfate drying merges, filter and concentrate.Be dissolved in the foam of gained in the hot ethyl acetate and, adopt ethyl acetate to obtain 247mg (54%) 9-[(2-pyridyl as eluent by silica gel shoroom temperature post) methyl]-4-hydroxyl-5-formamyl carbazole, be white solid.
1H NMR (DMSO-d6) δ 10.46 (s, 1H), 8.81 (br s, 1H), 8.46 (d, 1H, J=5.8 Hz), 8.36 (br s, 1H), 7.8 (dd, 1H, J=2.9 and 6.4 Hz), 7.67-7.59 (m, 1H), 7.47-7.41 (m, 2H), and 7.30-7.20 (m, 2H), 7.05 (d, 1H, J=7.9Hz), 6.87 (d, 1H, J=8.3 Hz), 6.57 (d, 1H, J=7.8 Hz), and5.73 (s, 2H) .IR (KBr, cm
-1) 3404,3051,1652,1618,1595,1582,1567,1559,1450,1436,1334,1266,1226,776,763 and 647.MS (ES) m/e 318 (M+1). ultimate analysis: C
19H
15N
3O
2: calculated value: C, 71.91; H, 4.76; N, 13.24 measured values: C, 72.11; H, 4.70; N, the 12.95D.{9-[(2-pyridyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
With methyl bromoacetate (0.08ml; 0.85mmol) handle the 9-[(2-pyridyl) methyl]-4-hydroxyl-5-formamyl carbazole (216mg, 0.68mmol) and Cs
2CO
3(stirred reaction mixture shows that up to tlc starting raw material reacts finish (2 hours) for 550mg, 1.69mmol) the 5ml DMF solution of mixture.Enriched mixture and with in the residue water-soluble (50ml).Extract 5 times with the saturated water layer of solid sodium chloride and with THF.With the organic layer that anhydrous sodium sulfate drying merges, filter and concentrate.With ethyl acetate development solid obtain 205mg (77%) the 9-[(2-pyridyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid methyl esters, be gray solid.
1H NMR (DMSO-d6) δ 8.47 (d, 1H, J=4.9 Hz), and 7.66-7.57 (m, 2H), 7.48 (br s, 1H), 7.38-7.27 (m, 2H), 7.24-7.19 (m, 2H), 7.19 (br s, 1H), 7.04 (d, 1H, J=7.3 Hz), 6.87 (d, 1H, J=7.8 Hz), 6.56 (d, 1H, J=7.8 Hz), 5.71 (s, 2H), 4.89 (s, 2H), and 3.69 (s, 3H) .IR (CHCl
3, cm
-1) 3380,3140,1737,1675,1500,1457,1354,1340,1242,1158,772, and 715.MS (ES) m/e 390 (M+1). ultimate analysis: C
22H
19N
3O
4: calculated value: C, 67.86; H, 4.92; N, 10.79 measured values: C, 67.75; H, 5.08; N, the 10.66E.{9-[(2-pyridyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid hydrochloride
With the 0.4ml 1N LiOH aqueous solution (0.4mmol) handle the 9-[(2-pyridyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters (75.0mg, 1.3ml THF 0.19mmol) and the slurries of 0.4ml methyl alcohol and in stirring at room mixture 16 hours.Concentrated reaction mixture also passes through reverse-phase chromatography purifying residue (Vydac C18 post, the 0.01%HCl/ acetonitrile/0.01%HCl/ water of employing 5%-40% gradient).Freeze-drying contains the fraction of product, obtain 75mg (96%) the 9-[(2-pyridyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid hydrochloride, be white powder.
1H NMR (DMSO-d6) δ
1H NMR (DMSO-d6) δ 8.50-8.46 (m, 1H), 7.71 (br s, 1H), 7.62-7.67 (m, 1H), 7.58 (d, 1H, J=8.3 Hz), 7.38 (br s, 1H), and 7.42-7.29 (m, 3H), 7.26-7.19 (m, 2H), (7.06 d, 1H, J=7.3 Hz), 6.87 (d, 1H, J=7.8 Hz), 6.58 (d, 1H, J=8.3 Hz), 5.73 (s, 2H) (s 2H), does not measure sour proton IR (KBr, cm to and 4.80
-1) 3381,1716,1637,1593,1580,1499,1454,1430,1330,1287,1157,1093,776 and720.MS (ES) m/e, 376 (M+1). ultimate analysis: C
21H
17N
3O
4HCl: calculated value: C, 61.24; H, 4.41; N, 10.20 measured values: C, 61.11; H, 4.25; N, 10.23
Embodiment 48{9-[(3-pyridyl) methyl]-5-formamyl carbazole-4-yl } preparation of ethoxyacetic acid
A.9-[(3-methyl pyridyl)]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
(500mg 3.05mmol) handles 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone (500mg with 3-pyrmethyl chloride hydrochloride, 2.06mmol), salt of wormwood (860mg, 18.8mmol) and the suspension of the sodium iodide (about 10mg) of catalytic amount, stirring at room 19.5 hours.Ethyl acetate extraction mixture 4 times will also be used in the mixture impouring water (100ml).Wash the organic layer 4 times of merging with water and, use anhydrous sodium sulfate drying, filter and concentrate with saturated brine washing 1 time.Obtain 550mg (80%) 9-[(3-pyridyl by flash chromatography on silica gel method purifying residue (with 5% methanol/ethyl acetate wash-out)) methyl] 5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone is white solid.
1H NMR (CDCl
3) δ 8.48 (d, 1H, J=2.9 Hz), 8.43 (br s, 1H), 7.31 (d, 1H, J=7.3 Hz), 7.25-7.09 (m, 5H), 5.29 (s, 2H), 3.97 (s, 3H), 2.80 (t, 2H, J=6.1 Hz), 2.49 (t, 2H, J=6.4 Hz), and 2.20-2.12 (m, 2H) .IR (CHCl
3, cm
-1) 1726,1656,1464,1444,1434,1289 and 1119.MS (ES) m/e, 335 (M+1). ultimate analysis: C
20H
18N
2O
3: calculated value: C, 71.84:H, 5.43; N, 8.38 measured values: C, 70.97; H, 5.89; N, the 8.53B.9-[(3-pyridyl) methyl]-4-hydroxy-5-methyl ester group carbazole
With sodium hydride (128mmol; 3.20mmol; The dispersion liquid of 60% mineral oil) handle the 9-[(3-pyridyl) methyl]-5-methoxycarbonyl-1, and 2-dihydro carbazole-4 (3H)-ketone (456mg, 3ml dioxane solution 1.31mmol), and stir the mixture 15 minutes of gained.To wherein being added dropwise to benzene sulfinic acid methyl esters (0.32ml; 2.45mmol) and reaction is heated to 70 ℃ shows that up to tlc all starting raw materials all react finish (2 hours).Reaction mixture is also used ethyl acetate (50ml) dilution.Separate organic layer,, use anhydrous sodium sulfate drying, filter and concentrate with saturated sodium bicarbonate aqueous solution washing 1 time with saturated brine washing 1 time.Obtain 400mg (92%) 9-[(3-pyridyl by silica gel cyclical chromatography purifying residue (with 20%, then 30%, then 50%, 75% ethyl acetate/hexane wash-out then)) methyl]-4-hydroxy-5-methyl ester group carbazole, be yellow solid.
1H NMR (DMSO-d6) δ 10.20 (s, 1H), 8.46 (d, 1H, J=2.0 Hz), (8.39 d, 1H, J=4.9 Hz), 7.73 (d, 1H, J=8.3 Hz), 7.43-7.37 (m, 2H), 7.28-7.21 (m, 2H), 7.15-7.08 (m, 2H), (6.56 d, 1H, J=7.8 Hz), 5.67 (s, 2H), and3.80 (s, 3H) .IR (KBr, cm
-1) 1722,1585,1459,1431,1331,1321,1292,1278,1136,781 and 763.MS (ES) m/e, 333 (M+1). ultimate analysis: C
20H
16N
2O
3: calculated value: C, 72.28; H, 4.85; N, 8.43 measured values: C, 72.37; H, 4.67; N, the 8.71C.9-[(3-pyridyl) methyl]-4-hydroxyl-5-formamyl carbazole
Handle the 9-[(3-pyridyl with the ammonia air-flow) methyl]-(362mg, the solution of 15mlTHF 1.09mmol) and the dense ammonium hydroxide aqueous solution of 60ml also makes it saturated to 4-hydroxy-5-methyl ester group carbazole.Add a cover and under agitation mixture heating up to 35 ℃ is shown starting raw material reaction finish (48 hours) up to tlc to reaction vessel.With the 5N aqueous hydrochloric acid mixture is neutralized to pH8, extracts mixture 2 times with the solid sodium chloride saturated mixture and with THF.Concentrate the organic layer that merges; the foam of gained is dissolved among a spot of THF and places use in advance on the ethyl acetate equilibrated silicagel column; adopt eluent ethyl acetate to obtain 255mg (74%) 9-[(3-pyridyl) methyl]-4-hydroxyl-5-formamyl carbazole, be yellow solid.
1H NMR (DMSO-d6) δ 10.46 (s, 1H), 8.79 (br s, 1H), 8.43 (d, 1H, J=1.5 Hz), 8.39 (dd, 1H, J=1.4 and 4.9 Hz), 8.35 (br s, 1H), 7.84 (d, 1H, J=7.8 Hz), and 7.48-7.22 (m, 6H), 7.13 (d, 1H, J=8.3 Hz), 6.58 (d, 1H, J=7.8 Hz), and 5.73 (s, 2H) .IR (KBr, cm
-1) 3436,3198 (br), 1629,1619,1599,1580,1564,1547,1444,1433,1329,1263, and 776.MS (ES) m/e 318 (M+1). ultimate analysis: C
19H
15N
3O
2: calculated value: C, 71.91; H, 4.76; N, 13.24 measured values: C, 72.10; H, 4.66; N, the 13.19D.{9-[(3-pyridyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters
With methyl bromoacetate (0.09ml; 0.95mmol) handle the 9-[(3-pyridyl) methyl]-4-hydroxyl-5-formamyl carbazole (225mg, 0.71mmol) and Cs
2CO
3(stirred reaction mixture shows that up to tlc starting raw material reacts finish (2 hours) for 580mg, 1.78mmol) the 5ml DMF solution of mixture.Enriched mixture and with in the residue water-soluble (50ml).Extract 5 times with the saturated water layer of solid sodium chloride and with THF.With the organic layer that anhydrous sodium sulfate drying merges, filter and concentrate.Obtain the 85mg{9-[(3-pyridyl with ethyl acetate development solid) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters, be gray solid.Adopt the mother liquor (with 0.5%, then 1%, 2% methyl alcohol/chloroform wash-out then) of silica gel circular chromatography purifying development gained to obtain 80mg product (common 165mg; 60%).
1H NMR (CDCl
3) δ 8.53 (br, 2H), 7.42-7.39 (m, 4H), 7.20 (d, 1H, J=7.8 Hz), 7.13 (br s, 1H), 6.98 (d, 1H, J=8.3Hz), 6.56 (d, 1H, J=7.9 Hz), 6.17 (br s, 1H), 5.91 (br s, 1H), 5.49 (s, 2H), 4.88 (s, 2H), and 3.79 (s, 3H) .IR (KBr, cm
-1) 3367,3161,1760,1733,1673,1577,1501,1458,1433,1418,1328,1216,1202,1180,1157,771, and 714.MS (ES) m/e 373 (M+-NH
2) and 390 (M+1) .E.{9-[(3-pyridyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid hydrochloride
With the 0.48ml 1N LiOH aqueous solution (0.48mmol) handle the 9-[(3-pyridyl) methyl]-5-formamyl carbazole-4-yl ethoxyacetic acid methyl esters (85.0mg, 1.5ml THF 0.22mmol) and the slurries of 0.48ml methyl alcohol and in stirring at room mixture 16 hours.Concentrated reaction mixture also passes through reverse-phase chromatography purifying residue (Vydac C18 post, the 0.01%HCl/ acetonitrile/0.01%HCl/ water of employing 5%-40% gradient).Freeze-drying contains the fraction of product, obtain 63mg (70%) the 9-[(3-pyridyl) methyl]-5-formamyl carbazole-4-yl the ethoxyacetic acid hydrochloride, be white powder.
1H NMR (DMSO-d6) δ 8.62-8.57 (m, 2H), 7.77-7.67 (m, 3H), 7.62-7.54 (m, 1H), 7.43-7.28 (m, 4H), 7.09 (d, 1H, J=6.3 Hz), 6.61 (d, 1H, J=7.8 Hz), 5.81 (s, 2H) and 4.80 (s, 2H), do not measure sour proton IR (KBr, cm
-1) 3424,3324,1728,1671,1655,1616,1595,1579,1500,1456,1421,1328,1203,1156, and 772.MS (ES) m/e 374 (M-1), 376 (M+1) ultimate analysis: C
22H
17N
3O
4HCl: calculated value: C, 61.24; H, 4.41; N, 10.20 measured values: C, 61.28; H, 4.25; N, 10.28
Embodiment 49[9-benzyl-4-formamyl-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-5-yl] the preparation methoxyl group-8-methyl isophthalic acid A.5-of ethoxyacetic acid, 2,3, the preparation of 4-tetrahydro carbazole-4-ethyl formate
2-ethoxycarbonyl-6-bromine pimelinketone (Sheehan and Mumaw at 55 ℃ of heating 1.87g (13.65mmol) 2-methyl-5-anisidines and 3.40g (13.65mmol), JACS, 72,2127 (1950)) 10ml anhydrous dimethyl formamide solution 13 hours, reaction mixture also is poured in the salt solution and with ether extraction 2 times.Water is used salt water washing extract 2 times then, with dried over mgso and concentrated.By silica gel chromatography purifying residue, adopt 10: 1 hexane/ethyl acetate mixture wash-outs, obtain the alkylating material of N-of 2.88g (69%), be the mixture of diastereomer.The zinc chloride of this mixture with 4.69g (34.4mmol) refluxed 10 hours in 90ml benzene.Evaporating solvent also distributes residue between 80ml1N hydrochloric acid and 80ml ethyl acetate, and then with ethyl acetate extraction 1 time.Water is used salt water washing organic layer then, with anhydrous magnesium sulfate drying and the concentrated subhead compound that obtains 2.60g (95%).Fusing point 119-122 ℃.Ultimate analysis: calculated value: C, 71.06; H, 7.37; N, 4.87 measured values: C, 71.35; H, 7.25; N, 4.92B. prepare 9-benzyl-5-methoxyl group-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-ethyl formate
With 1.58g 5-methoxyl group-8-methyl isophthalic acid, 2,3, the 5ml dimethyl formamide solution of 4-tetrahydro carbazole-4-ethyl formate is added in the 5ml dimethyl formamide solution of 0.24g sodium hydride (60% in mineral oil) and at room temperature stirred 30 minutes.Adding potassiumiodide (90mg) and 0.75ml bromotoluene and stirring reaction then spends the night.Reaction mixture is poured in the 75ml saturated ammonium chloride solution, then uses the ether extraction secondary, with extract elder generation water, use the salt water washing then again, with dried over mgso and concentrated.By the silica gel chromatography residue, obtain 1.09g (53%) subhead compound with the mixture wash-out of hexane/ethyl acetate.
ESIMS m/e 378 (M
++ 1) NMR (300MHz, CDCl
3): δ 7.28-7.19 (m, 3H); 6.84 (d, J=7.4,2H); 6.67 (d, J=7.8,1H); 6.33 (d, J=7.9,1H); 5.55and 5.39 (ABq, J=7.8,2H); 4.17 (q+m, J=6.9,3H); 3.80 (s, 3H); 2.64 (dt, J=16.1,5.3,1H); 2.48 (dt, J=16.6,6.9,1H); 2.41 (s, 3H); 2.05 (m, 2H); 1.95 (m, 1H); 1.83 (m, 1H); 1.25 (3H) .C. prepares 9-benzyl-5-methoxyl group-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide for t, J=7.3
Cool off the slurries of 0.38g ammonium chloride in the 15ml dry toluene with ice bath, and handle with the toluene solution of 3.5ml 2.0M trimethyl aluminium.In the mixture of stirring at room gained 1 hour, so add the 9-benzyl-5-methoxyl group-8-methyl isophthalic acid that is dissolved in the 0.762g (2.02mmol) in 10ml toluene and the 1ml methylene dichloride, 2,3,4-tetrahydro carbazole-4-ethyl formate.Spend the night cooling and with 20ml 5% aqueous hydrochloric acid stopped reaction at 50 ℃ of heated mixt.The ethyl acetate extract (3x100ml) that water merges with the salt water washing then is with dried over mgso and the concentrated subhead compound that obtains 0.693g (98%).
ESIMS m/e 349 (M
++ 1) NMR (300MHz, CDCl
3): δ 7.25 (m, 3H); 6.83 (d, J=7.2,2H); 6.74 (d, J=7.8,1H); 6.40 (d, J=7.8,1H); 5.93 (br, 1H); 5.54 and5.45 (ABq, J=17.7,2H); 5.42 (br, 1H); 4.14 (br, 1H); 3.87 (s, 3H); 2.65 (dt, J=16.4,4.1,1H); 2.55-2.36 (m, 2H); 2.45 (s, 3H); 1.97-1.86 (m, 3H) .D. preparation [9-benzyl-4-formamyl-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid methyl esters
With 0.661g9-benzyl-5-methoxyl group-8-methyl isophthalic acid, 2,3, the 50ml anhydrous methylene chloride solution of 4-tetrahydro carbazole-4-methane amide is cooled to-40 ℃, and handles by being added dropwise to the clean boron tribromide of 1.8ml.Stirring reaction 2 hours and add 1N hydrochloric acid and make its termination at room temperature by being poured into ice neutralization.With dichloromethane extraction mixture 2 times, with organic layer with dried over mgso and concentrate and obtain the dimethylated compound of 0.625g.
In ice bath, cool off the solution of the 10ml dimethyl formamide of the above-mentioned intermediate of 0.55g, and handle with 1.61g cesium carbonate and 0.16ml methyl bromoacetate.After at room temperature stirring 1 hour, reaction mixture is poured in the water and with ethyl acetate extraction 2 times.Water is used salt water washing extract then, with dried over mgso and concentrated.By the silica gel chromatography residue, carry out wash-out with the 0-2% ethanol/methylene and obtain 0.46g (69%) subhead compound.209 ℃ of fusing points.Ultimate analysis: calculated value: C70.92; H6.45; N6.89 measured value: C70.85; H6.19; N6.98E. prepare [9-benzyl-4-formamyl-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid
Handle 64mg (0.157mmol) [9-benzyl-4-formamyl-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-5-yl] the 2ml tetrahydrofuran (THF) of ethoxyacetic acid methyl esters and the solution of 7ml methyl alcohol with 0.5ml 2N aqueous sodium hydroxide solution, and at room temperature stir and spend the night.Evaporating solvent also distributes residue between ethyl acetate and 1N hydrochloric acid soln.After extracting once more with ethyl acetate, with salt water washing extract, with dried over mgso and concentrate the title compound that obtains quantitative yield (62mg).
ESIMS m/e 393 (M
++ 1), 391 (M
+-1) .NMR (300MHz, d
6-DMSO): δ 12.98 (br, 1H); 7.30-7.18 (m, 3H); 6.82 (d+br, J=7.0,3H); 6.73 (br, 1H); 6.59 (d, J=7.9,1H); 6.26 (d, J=7.9,1H); 5.53 and 5.45 (ABq, J=18.1,2H); 4.62 (s, 2H); 3.96 (br, 1H); 2.63 (m, 1H); 2.43 (m, 1H); 2.34 (s, 3H); 2.04 (m, 2H); 1.78 (m, 2H). ultimate analysis calculated value: C70.39; H6.16; N7.14 measured value: C70.41; H6.44; N6.88
Embodiment 50 preparation [9-benzyl-5-formamyl-1-methyl carbazole-4-yl] ethoxyacetic acid A. prepare 5-formamyl-4-methoxyl group-1-methyl carbazole
Handle 0.805g 9-benzyl-5-methoxyl group-8-methyl isophthalic acid with 1.1g 5% palladium charcoal, 2,3, the 24ml card of 4-tetrahydro carbazole-4-methane amide is finished alcoholic solution and was refluxed 6 hours under the situation of ingress of air.After the cooling, wash this pad by the Celite pad filtering solution and with ethyl acetate.With ether dilution filtrate and wash with water 4 times, with dried over mgso and concentrate.By the silica gel chromatography residue, carry out the carbazole that wash-out obtains 0.166g (28%) debenzylation with the 0-4% ethanol/methylene.
ESIMS m/e 255 (M
++ 1), 253 (M
+-1) NMR (300MHz, CDCl
3): δ 8.13 (br, 1H); 7.51 (d, J=8.1,1H); 7.40 (t, J=7.6,1H); 7.32 (d, J=7.2,1H); 7.18 (d, J=7.8,1H); 6.60 (d, J=8.0,1H); 5.68 (br, 2H); 3.99 (s, 3H); 2.50 (s 3H) .B. prepares 9-benzyl-5-formamyl-4-methoxyl group-1-methyl carbazole
The 1.1ml dimethyl formamide solution of 0.148g 5-formamyl-4-methoxyl group-1-methyl carbazole is added in the 0.4ml dimethyl formamide solution of 0.026g sodium hydride (60% in mineral oil) and stirring at room 60 minutes.Adding bromotoluene (0.076ml) and stirring reaction then spends the night.Reaction mixture is poured in the 20ml saturated ammonium chloride solution and with ethyl acetate extraction 2 times, water is used salt water washing extract then, with dried over mgso and concentrate.With hexane rinsing residue, it is dissolved in the methylene dichloride again, filter and the concentrated 0.21g subhead compound that obtains.FDMS m/e 344 (M
+) ultimate analysis: calculated value: C76.72; H5.85; N8.13 measured value: C75.20; H6.19; N7.54C. prepare [9-benzyl-5-formamyl-1-methyl carbazole-4-yl] ethoxyacetic acid methyl esters
The 4ml dimethyl formamide solution of 0.23g 9-benzyl-5-formamyl-4-methoxyl group-1-methyl carbazole is added in the 1ml sulfur alcohol sodium solution (60% dispersion liquid and 0.22ml sulfur alcohol with the 0.116g sodium hydride in nitrogen atmosphere prepare), and 110 ℃ of heating 5 hours.Reaction mixture is also used ethyl acetate extraction 2 times in the impouring 20ml 1N hydrochloric acid.Water is used salt water washing extract then, with dried over mgso and concentrated.By silica gel chromatography purifying residue, carry out the dimethylated intermediate that wash-out obtains 0.146g (66%) with the 0-1% ethanol/methylene.The 1.5ml dimethyl formamide solution of the above-mentioned intermediate of 0.146g is added in the 0.5ml dimethyl formamide solution of 0.021g sodium hydride (60% in mineral oil).In stirring at room after 10 minutes, add the 0.054m methyl bromoacetate, at room temperature stir 5 hours after, reaction mixture is poured in the water and with ethyl acetate extraction 2 times.Water is used salt water washing extract then, with dried over mgso and concentrated.By the silica gel chromatography residue, carry out wash-out with the 0-2% ethanol/methylene and obtain 0.10g (56%) subhead compound.Fusing point 228-230 ℃ of ESIMS m/e 403 (M
++ 1) ultimate analysis: calculated value: C71.63; H5.51; N6.96 measured value: C71.34; H5.60; N6.70D. prepare [9-benzyl-5-formamyl-1-methyl carbazole-4-yl] ethoxyacetic acid
Handle 32mg (0.0795mmol) [9-benzyl-5-formamyl-1-methyl carbazole-4-yl] the 1ml tetrahydrofuran (THF) of ethoxyacetic acid methyl esters and the slurries of 3.5ml methyl alcohol with 0.3ml 2N aqueous sodium hydroxide solution, and at room temperature stir and spend the night.Evaporating solvent also distributes residue between 1: 1 ethyl acetate/tetrahydrofuran (THF) and 0.2N hydrochloric acid soln.After extracting once more with ethyl acetate/tetrahydrofuran (THF), with salt water washing extract, with dried over mgso and concentrate and obtain title compound (27mg).Fusing point 253-254 ℃ of ESIMS m/e 389 (M
++ 1), 387 (M
+-1) NMR (300MHz, d
6-DMSO): δ 12.83 (br, 1H); 7.75 (br, 1H); 7.53 (d, J=8.2,1H); 7.41-7.34 (m, 2H); 7.28-7.17 (m, 3H); 7.07 (m, 2H); 6.90 (d, J=7.2,2H); 6.49 (d, J=8.1,1H); 5.89 (s, 2H); 4.79 (s, 2H); 2.52 (s, 3H).
Embodiment 51[9-benzyl-4-formamyl-8-fluoro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid A. prepares carbonic acid (2-chloro-4-fluorophenyl)-ethyl ester
The solution of cooling 19.16g 2-chloro-4-fluorophenol in 65.4ml 2N sodium hydroxide solution in ice bath, and be added dropwise to the 16.3ml Vinyl chloroformate and handle, at room temperature stir and spend the night, then extract with 100ml water dilution two-phase reaction mixture with 1: 1 pentane/ether mixture of 300ml.Use the 0.02N sodium hydroxide solution, water is used the saline water extraction mixture 3 times then.After drying and the evaporation, obtain 27.63g (97%) subhead compound.
NMR (300MHz, CDCl
3): δ 7.23-7.18 (m, 2H); 7.00 (dt, J=8.4,2.7,1H); 4.35 (q, J=7.1,2H); 1.40 (3H) .B. prepares carbonic acid (2-chloro-4-fluoro-5-nitrophenyl)-ethyl ester for t, J=7.1
In ice bath, cool off the 60ml dichloromethane solution of 27.63g carbonic acid (2-chloro-4-fluorophenyl)-ethyl ester, and be added dropwise to 1: 2 mixture process of the 31.86g nitrosonitric acid (90%) and the vitriol oil.At room temperature stirred the mixture 2 hours, then with ice-cooled and handle with the same nitrating mixture of 4.5g again.In the stirring at room mixture overnight, be poured in 200ml ice and the water and with dichloromethane extraction 2 times, water is used salt water washing extract then, with the also concentrated subhead compound that obtains 33.01g (99%) of dried over mgso.Mp.50-51 ℃ of ultimate analysis calculated value: C41.01; H2.68; N5.31; Cl13.45 measured value: C41.03; H2.59; N5.38; Cl13.71C. prepare 2-chloro-4-fluoro-5-Nitroanisole
With the 100ml dimethyl formamide solution of 18.6g cesium carbonate, 7.1ml methyl iodide and 7ml methyl alcohol processing 15.0g carbonic acid (2-chloro-4-fluoro-5-nitrophenyl)-ethyl ester and in stirred overnight at room temperature.To also use ether extraction 2 times in the reaction mixture impouring water, water is used salt water washing extract then, with dried over mgso and the concentrated 11.4g subhead compound that obtains.Mp.69-70 ℃ of Ex, 57, C ultimate analysis calculated value: C40.90; H2.45; N6.81; The Cl17.25 measured value; C41.20; H2.48; N6.70; Cl17.44D. prepare 2-fluoro-5-anisidine
The solution 4 hours of the 90ml ethanol of hydrogenation 5.63g2-chloro-4-fluoro-5-Nitroanisole and 5ml triethylamine under 60 pounds of/square inch pressure of room temperature and 1.0g 5% palladium sketching charcoal spare, filtration catalizer and evaporating solvent.In chloroform, filter, then evaporation with residue slurrying and by silica gel plug.By silica gel chromatography purifying residue, adopt hexane/chloroform mixture wash-out to obtain the subhead compound of 2.77g (72%).mp.253-254℃。
NMR (300MHz, CDCl
3): δ 6.88 (dd, J=10.6,8.9,1H); 6.32 (dd, J=7.4,3.0,1H); 6.20 (dt, J=8.9,3.2,1H); 3.73 (s, 3H); 3.72 (br, 2H) .E. prepares N-benzyl-2-fluoro-5-anisidine
This step is to copy Tietze and the described method of Grote, sees Chem Ber.126 (12), 2733 (1993).Handle the solution of the 48ml methyl alcohol of 2.73g 2-fluoro-5-anisidine and 2.67g phenyl aldehyde with the 3.43g zinc chloride, in ice bath, cool off then.Divide in 30 minutes short run at room temperature (in small poroom temperature) add sodium cyanoborohydride (1.58g), and in stirring at room mixture 5 hours.Behind the evaporating solvent, in 40ml 1N sodium hydroxide solution,, use ether extraction then 2 times with residue slurrying.Water is used salt water washing extract then, with dried over mgso and concentrated.Obtain 2.61g with hexane recrystallization residue, and, adopt 20: 1 hexane/ether wash-outs to obtain 1.4g subhead compound (90%) by silica gel chromatography purifying mother liquor.mp.56-58℃。Ultimate analysis: calculated value: C72.71; H6.10; N6.06 measured value: C72.51; H6.06; N5.99F. prepare 9-benzyl-5-methoxyl group-8-fluoro-1,2,3,4-tetrahydro carbazole-4-ethyl formate
The 20ml anhydrous tetrahydrofuran solution of cooling 0.62g N-benzyl-2-fluoro-5-anisidine in ice bath, and with the toluene solution processing of two (trimethyl silyl) potassium amides of 11.3ml 0.5M.Stir after 30 minutes, add the 4ml tetrahydrofuran solution of 0.74g 2-ethoxycarbonyl-6-bromine pimelinketone (Sheehan and Mumaw, JACS, 72,2127 (1950)), and in 2 hours, make reaction mixture slowly be warmed up to room temperature.Make the stopping of reaction and use ether extraction 2 times with saturated ammonium chloride solution, water is used salt water washing extract then, with dried over mgso and concentrated.By silica gel chromatography purifying residue, adopt hexane/ether mixture wash-out to obtain the N-alkylation intermediate diastereomer of 0.796g (74%).This mixture refluxed in 20ml benzene with the 0.99g zinc chloride spend the night.Evaporating solvent also distributes residue between 25ml 1N hydrochloric acid and 25ml ethyl acetate, extract 1 time with ethyl acetate then again.Water is used salt water washing organic layer then, with dried over mgso and the concentrated subhead compound that obtains 0.734g (96%).ESIMS m/e 382 (M
++ 1) ultimate analysis: calculated value: C72.42; H6.34; N3.67 measured value: C72.20; H6.26; N3.70G. prepare 9-benzyl-5-methoxyl group-8-fluoro-1,2,3,4-tetrahydro carbazole-4-formyl is pressed
Handle 9-benzyl-5-methoxyl group-8-fluoro-1 by the described similar mode of embodiment 49 step C, 2,3,4-tetrahydro carbazole-4-ethyl formate (0.722g), and, obtain 0.482g (72%) subhead compound with 1% ethanol/methylene wash-out by the silica gel chromatography purifying.ESIMS m/e 353 (M
++ 1) ultimate analysis: calculated value: C 71.57; H 6.01; N 7.95 measured values: C 71.42; H 5.83; N 7.75H. prepares [9-benzyl-4-formamyl-8-fluoro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid methyl esters
Transform 9-benzyl-5-methoxyl group-8-fluoro-1 by the described similar mode of embodiment 49 step D, 2,3,4-tetrahydro carbazole-4-methane amide (0.170g), by the silica gel chromatography purifying, obtain the subhead compound of 85mg (50%) with 0-1% ethanol/methylene wash-out.Mp.183-185 ℃ of ultimate analysis: calculated value: C67.31; H5.65; N6.82 measured value: C67.58; H5.48; N6.95I. prepare [9-benzyl-4-formamyl-8-fluoro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid
Press the described similar mode hydrolysis of embodiment 50 step D [9-benzyl-4-formamyl-8-fluoro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid methyl esters (71mg) and obtain the title compound of 65mg.
ESIMS?m/e?397(M
++1)，395(M
+-1)NMR(300MHz，d
6-DMSO)：δ13.03(br，1H)；7.31-7.19(m，3H)；6.97(d，J＝7.4，2H)；6.95(br，1H)；6.70(d，J＝3.8，1H)；6.67(dd，J＝12.4，3.9，1H)；6.28(dd，J＝8.5，2.6，1H)；5.39(ABq，2H)；4.64(s，2H)；3.92(br，1H)；2.71(m，1H)；2.44(m，1H)；2.02(m，2H)；1.76(m，2H).
Embodiment 52 preparation [9-benzyl-5-formamyl-1-fluorine carbazole-4-yl] ethoxyacetic acid A. prepare 9-benzyl-5-formamyl-4-methoxyl group-1-fluorine carbazole
Under nitrogen atmosphere, use 0.59g 2,3-two chloro-5; 6-dicyano-1,4-benzoquinones are handled 0.458g 9-benzyl-5-methoxyl group-8-fluoro-1,2,3, the no Shui dioxane solution of the 13ml of 4-tetrahydro carbazole-4-methane amide, and refluxed 1 hour.Reaction mixture is also filtered and with the washing precipitation of 15ml diox, filtrate and washing lotion is poured in the saturated sodium bicarbonate solution, and with ethyl acetate extraction 3 times.Use saturated sodium bicarbonate, water and then with salt water washing extract is with dried over mgso with concentrate.By silica gel chromatography purifying residue, adopt methylene dichloride/0-2% methanol-eluted fractions to obtain 0.45g subhead compound.ESIMS m/e 349 (M
++ 1) ultimate analysis calculated value: C72.42; H4.92; N8.04 measured value: C72.35; H4.81; N7.88B. prepare [9-benzyl-5-formamyl 1-fluorine carbazole-4-yl] ethoxyacetic acid methyl esters
The 25ml dichloromethane solution of cooling 0.45g 9-benzyl-5-formamyl-4-methoxyl group-1-fluorine carbazole in ice bath, the dichloromethane solution that is added dropwise to 12ml 1.0M boron tribromide is handled.In 2 hours, make sluggish be warmed up to room temperature, by making it to end in the impouring ice, add 50ml 1N hydrochloric acid then thereupon.Extract mixture with methylene dichloride (3x200ml), and with extracting solution with dried over mgso and concentrate and obtain the dimethylated intermediate of 0.35g (78%).Carry out the subhead compound that purifying obtains 0.166g (64%) with (0.215g) alkylation of this intermediate and by the similar mode of embodiment GH1 step D.Fusing point 190-191 ℃ ultimate analysis: calculated value: C67.97; H4.71; N6.89 measured value: C67.81; H4.94; N6.96C. prepare [9-benzyl-5-formamyl-1-fluorine carbazole-4-yl] ethoxyacetic acid
By the described similar mode hydrolysis of embodiment 50 step D with separate [9-benzyl-5-formamyl-1-fluorine carbazole-4-yl] ethoxyacetic acid methyl esters (56mg) and obtain the subhead compound of 54mg.
NMR (300MHz, d
6-DMSO): δ 12.92 (br, 1H); 7.70 (m, 2H); 7.45 (t, J=7.5,1H); 7.39 (br, 1H); 7.28-7.17 (m, 4H); 7.12 (d, J=7.2,1H); 7.07 (d, J=7.0,2H); 6.51 (dd, J=8.8,2.7,1H); 5.77 (s, 2H); 4.80 (s, 2H). ultimate analysis: calculated value: C67.34; H4.37; N7.14 measured value: C66.92; H4.49; N6.77
Embodiment 53 preparation [9-benzyl-4-formamyl-8-chloro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid A. prepare 9-benzyl-5-methoxyl group-8-chloro-1,2,3,4-tetrahydro carbazole-4-ethyl formate
Prepare N-benzyl-2-chloro-5-anisidine by the described similar mode of embodiment 51 step e.Transform by the 60ml anhydrous tetrahydrofuran solution of the described similar mode of embodiment GH3 step F 2.07gN-benzyl-2-chloro-5-anisidine, and by the silica gel chromatography purifying, carry out wash-out with 15: 1 hexane/ethyl acetate, obtain the subhead compound of 1.65g (50%).Ex.59, A.ESIMS m/e 398 (M
++ 1) NMR (300MHz, CDCl
3): δ 7.29-7.19 (m, 3H); 6.92 (m, 3H); 6.36 (d, J=8.4,1H); 5.87 (d, J=17.4,1H); 5.53 (d, J=17.3,1H); 4.16 m, 3H); 3.81 (s, 3H); 2.66 (dt, J=16.3,5.4,1H); 2.49 (dt, J=16.6,6.6,1H); 2.05 (m, 2H); 1.98-1.79 (m, 2H); 1.25 (t, 3H) .B. prepares 9-benzyl-5-methoxyl group-8-chloro-1,2,3,4-tetrahydro carbazole-4-methane amide
Transform 9-benzyl-5-methoxyl group-8-chloro-1,2,3 by the described similar mode of embodiment 51 step G, 4-tetrahydro carbazole-4-ethyl formate (1.65g) obtains the subhead compound of 1.54g (100%).Ex.59,205-8 ℃ of ESIMS m/e 369 (M of B. fusing point
++ 1) C. preparation-[9-benzyl-4-formamyl-8-chloro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid methyl esters
Transform 9-benzyl-5-methoxyl group-8-chloro-1,2,3 by the described similar mode of embodiment 51 step H, 4-tetrahydro carbazole-4-methane amide (0.405g), and, carry out wash-out with methylene dichloride/0-1.5% methyl alcohol by the silica gel chromatography purifying, obtain 0.248g (53%) subhead compound.Ex.59,185-186 ℃ of C. fusing point.Ultimate analysis: calculated value: C64.71; H5.43; N6.56 measured value: C64.98; H5.39; N6.67D. prepare [9-benzyl-4-formamyl-8-chloro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid
Press the described similar mode hydrolysis of embodiment 49 step e [9-benzyl-4-formamyl-8-chloro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid methyl esters (58mg) and obtain the 54mg title compound.
Ex.59, D.ESIMSm/e 413 (M
++ 1), 411 (M
+-1) NMR (300MHz, d
6-DMSO): δ 13.05 (br, 1H); 7.30-7.18 (m, 3H); 6.90 (d+m, J=7.6,4H); 6.73 (br, 1H); 6.39 (d, J=8.3,1H); 5.77 and 5.58 (ABq, J=17.5,2H); 4.67 (s, 2H); 3.95 (br, 1H); 2.66 (m, 1H); 2.43 (m, 1H); 2.00 (m, 2H); 1.76 (m, 2H). ultimate analysis calculated value: C64.00; H5.13; N6.78; The Cl8.59 measured value; C62.82; H5.34; N6.22; Cl7.99
Embodiment 54 preparation [9-benzyl-5-formamyl-1-chlorine carbazole-4-yl] ethoxyacetic acid A. prepare 9-benzyl-5-formamyl-4-methoxyl group-1-chlorine carbazole
Press the described similar mode oxidation 1.0g9-benzyl of embodiment 51 steps A-5-methoxyl group-8-methyl isophthalic acid, 2,3,4-tetrahydrochysene-4-methane amide, and, obtain the subhead compound of 0.66g (67%) with methylene dichloride/0-1% methanol-eluted fractions by the silica gel chromatography purifying.FDMS m/e 364 (M
+) ultimate analysis calculated value: C69.14; H4.70; N7.68; The Cl9.72 measured value; C69.40; H4.64; N7.49; Cl9.98B. prepare 5-formamyl-4-hydroxyl-1-chlorine carbazole
The 40ml dichloromethane solution of cooling 0.66g 9-benzyl-5-formamyl-4-methoxyl group-1-chlorine carbazole in ice bath, the dichloromethane solution that is added dropwise to 14ml 1.0M boron tribromide is handled.In 2 hours, make sluggish be warmed up to room temperature, by making it to end in the impouring ice, add 50ml 1N hydrochloric acid then thereupon.Extract mixture with methylene dichloride (3x200ml), and with extracting solution salt water washing, again with dried over mgso and concentrated.Precipitation appears in water layer, uses ethyl acetate extraction 2 times thereupon, uses the salt water washing, with dried over mgso and the concentrated 0.287g subhead compound that obtains.The residue that obtains is for the first time passed through the silica gel chromatography purifying, obtain other 93mg subhead compound (overall yield 80%) with 0.5% ethanol/methylene wash-out.
ESIMS m/e259 (M
+-1) NMR (300MHz, d
6-DMSO): δ 11.79 (s, 1H); 10.76 (s, 1H); 8.87 (br s, 1H); 8.41 (br s, 1H); 7.77 (t, J=4.6,1H); 7.48 (d, J=4.2,2H); 7.34 (d, J=8.5,1H); 6.54 (d, J=8.5,1H) .C. preparation [5-formamyl-1-chlorine carbazole-4-yl] ethoxyacetic acid methyl esters
The 6ml tetrahydrofuran solution of 0.28g 5-formamyl-4-hydroxyl-1-chlorine carbazole is added in the 1ml tetrahydrofuran solution of 0.043g sodium hydride (60%, in mineral oil), and stirring at room 60 minutes.In reaction, add methyl bromoacetate (0.11ml) and stir and to spend the night, reaction mixture is poured in the 20ml saturated ammonium chloride solution, use ethyl acetate extraction then 2 times.Water is used salt water washing extract then, with dried over mgso and concentrated.By silica gel chromatography purifying residue, with chloroform, 2: 1 chloroform/eluent ethyl acetates obtain the subhead compound of 0.16g (45%) then.
ESIMS m/e 333 (M
++ 1), 335 (M
++ 3), 331 (M
+-1) NMR (300MHz, d
6-DMSO): δ 11.73 (s, 1H); 7.56 (d, J=8.1,1H); 7.50 (br s, 1H); 7.43-7.35 (m, 2H); 7.18 (br s, 1H); 7.06 (d, J=7.8,1H); 6.56 (d, J=8.6,1H); 4.90 (s, 2H); 3.70 (s, 3H) .D. preparation [9-benzyl-5-formamyl-1-chlorine carbazole-4-yl] ethoxyacetic acid methyl esters
With 78mg[5-formamyl-1-chlorine carbazole-4-yl] the 0.8ml anhydrous dimethyl formamide solution of ethoxyacetic acid methyl esters is added in the 0.2ml dimethyl formamide solution of 10mg sodium hydride (60%, in mineral oil), and stirring at room 15 minutes.Adding bromotoluene (0.031ml) and stirring reaction then spends the night.Reaction mixture is poured in the water and with 1ml 1N hydrochloric acid soln acidifying with ethyl acetate extraction 2 times, water (3x) is used salt water washing extract then, with dried over mgso and concentrated.By silica gel chromatography purifying residue, obtain 40mg subhead compound with 0-2% ethanol/methylene wash-out.ESIMS m/e 423 (M
++ 1) 425 (M
++ 3) NMR (300MHz, CDCl
3): δ 7.43-7.22 (m, 7H); 7.06 (d, J=7.3,2H); 6.51 (d, J=8.6,1H); 6.05 (s, 2H); 5.80 (br, 2H); 4.88 (s, 2H); 3.83 (s, 3H) .E. preparation [9-benzyl-5-formamyl-1-chlorine carbazole-4-yl] ethoxyacetic acid
Obtain the title compound of 14mg by the described similar mode hydrolysis of embodiment 50 step D [9-benzyl-5-formamyl-1-chlorine carbazole-4-yl] ethoxyacetic acid methyl esters (15mg).mp.?240-2℃?ESIMS?m/e?409(M
++1)，411(M
++3)，407(M
+-1)NMR(300MHz，d
6-DMSO)：δ12.94(br，1H)；7.70(br，1H)；7.61(d，J＝8.3，1H)；7.43(t，J＝7.8，1H)；7.36(m，2H)；7.28-7.19(m，3H)；7.13(d，J＝7.2，1H)；6.99(d，J＝7.4，2H)；6.63(d，J＝8.6，1H)；6.08(s，2H)；4.83(s，2H).
Embodiment 55 preparations [the 9-[(cyclohexyl) methyl-5-formamyl carbazole-4-yl] ethoxyacetic acid
A.9-[(methyl cyclohexyl)]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
At 0 ℃ with cyclohexyl methyl bromine (0.631ml, 4.52mmol) processing 5-methoxycarbonyl-1, and 2-dihydro-9H-carbazole-4 (3H)-ketone (1.0g, 4.11mmol), sodium iodide of catalytic amount (about 10mg) and salt of wormwood (1.1g, the suspension of 10ml DMF 8.22mmol).After stirred overnight at room temperature, add other 0.63ml cyclohexyl methyl bromine, and at the mixture 3 hours of 60 ℃ of heating gained.To extract in the mixture impouring water (30ml) and with ethyl acetate (2x25ml).The organic layer that water (4x50ml) washing merges is used anhydrous sodium sulfate drying, filters and vacuum concentration.Obtain 1.36g (4.01mmol by silica gel cyclical chromatography purifying residue (adopting 20%-40% ethyl acetate/hexane gradient elution); 97%) methyl 9-[(cyclohexyl)]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone is white foam.
IR (CHCl
3, cm
-1) 3011,2932,2857,1725,1649,1469,1446,1288 and 1120.MS (ES) m/e, 340 (M+1), 453 (M+AcO
-) .FAB HRMS m/e, C
21H
26NO
3Calculated value be 340.1913, measured value is 340.1916 (M+1) C
21H
25NO
3Results of elemental analyses: calculated value: C, 74.31; H, 7.42; N, 4.13 measured values: C, 72.65; H, 7.39; N, the 4.70B.9-[(cyclohexyl) methyl]-4-hydroxy-5-methyl ester group carbazole
At 80 ℃ of heating 9-[(cyclohexyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone (1.16g, 3.42mmol) and 2,3-two chloro-5,6-dicyano-1, (853mg, 20ml toluene solution 3.76mmol) 3 hours directly obtain 259mg (0.768mmol by silica gel chromatography (using the methylene dichloride wash-out) with reaction mixture to the 4-benzoquinones; 22%) methyl 9-[(cyclohexyl)]-4-hydroxy-5-methyl ester group carbazole, be yellow oil, it can slowly solidify.MS (ES) m/e 338 (M+1), 336 (M-1) C
21H
23NO
3Results of elemental analyses: calculated value: C, 74.75; H, 6.87; N, 4.15 measured values: C, 74.95; H, 6.99; N, the 4.42C.9-[(cyclohexyl) methyl]-4-hydroxyl-5-formamyl carbazole
Handle the 9-[(cyclohexyl with the ammonia air-flow) methyl]-4-hydroxy-5-methyl ester group carbazole (205mg, the 0.608mmol) solution in 5mlTHF and the dense ammonium hydroxide aqueous solution of 20ml, and make it saturated.Add a cover to reaction vessel, and under agitation show that up to tlc starting raw material reacts finish (20 hours) in 35 ℃ of following heated mixt.Evaporation THF also filters water layer.The green solid precipitation is dissolved among the THF also by silica gel cyclical chromatography purifying (using the methylene dichloride wash-out).Obtain the title compound of 138mg (70%) with the foam of ether development gained, be gray solid IR (KBr, cm
-1) 3418,3200,3131,1629,1600,1443,1261,778.' FAB HRMS m/e, C
20H
23N
2O
2Calculated value be 323.1760, measured value is 323.1760 (M+1) D.[9-[(cyclohexyl) methyl]-5-formamyl carbazole-4-yl] the ethoxyacetic acid methyl esters
With methyl bromoacetate (0.023ml; 0.242mmol) handle the 9-[(cyclohexyl) methyl]-4-hydroxyl-5-formamyl carbazole (60mg, 0.186mmol) and Cs
2CO
3(150mg, 0.460mmol) the 2ml DMF solution of mixture stirring at room reaction 2 hours, are used ethyl acetate and water (10ml separately) dilution then.With the saturated water layer of solid sodium chloride, and with its usefulness ethyl acetate (2x10ml) extraction; With organic layer water (2x25ml) washing that merges, use anhydrous sodium sulfate drying, filter and vacuum concentration.Obtain 45mg (0.114mmol by flash chromatography on silica gel purifying residue crude product (with 0-90% ethyl acetate/hexane gradient elution); 61%) title compound is gray solid.MS (ES) m/e 395 (M+1), 378 (M+H-NH
3), 453 (M+AcO
-) C
23H
26N
2O
40.3H
2The results of elemental analyses of O: calculated value: C, 69.08; H, 6.71; N, 7.01 measured values: C, 69.13; H, 6.71; N, the 7.09E.[9-[(cyclohexyl) methyl]-5-formamyl carbazole-4-yl] ethoxyacetic acid
Handle [9-[(cyclohexyl) methyl]-5-formamyl carbazole-4-yl with the 0.1ml 1N LiOH aqueous solution (0.1mmol)] ethoxyacetic acid methyl esters (20mg, 0.3ml THF 0.051mmol) and the slurries of 0.1ml methyl alcohol and in stirring at room mixture 2 hours.Remove organic solvent with 0.2N hydrochloric acid acidizing reaction and vacuum.Filtering white precipitate from water layer, and it is obtained 16mg (0.042mmol with ether rinse; 83%) title acid compound is white powder.MS (ES) m/e 381 (M+1), 364 (M+H-NH
3), 379 (M-1) C
22H
24N
2O
4Results of elemental analyses: calculated value: C, 69.46; H, 6.36; N, 7.36 measured values: C, 69.34; H, 6.35; N, 7.29
Embodiment 56 preparations [the 9-[(cyclopentyl) methyl-5-formamyl carbazole-4-yl] ethoxyacetic acid
A.9-[(cyclopentyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone
With cyclopentyl-methyl chlorine (JOC, 1964,29,421-423; 400mg 3.37mmol) handles 5-methoxycarbonyl-1, and 2-dihydro-9H-carbazole-4 (3H)-ketone (820g, 3.37mmol), sodium iodide (about 10mg) and salt of wormwood (930mg, the suspension of 6ml DMF 6.74mmol) of catalytic amount.After stirred overnight at room temperature, add other 800mg cyclopentyl-methyl chlorine and 1g sodium iodide, and 80 ℃ of mixture overnight that heat gained.Add other 800mg cyclopentyl-methyl chlorine and 2.2g cesium carbonate, and in 80 ℃ of reacting by heating mixtures 24 hours.Add 1.6g cyclopentyl-methyl chlorine again, and in 80 ℃ of reacting by heating mixtures 3 days.To extract in the mixture impouring water (30ml) and with ethyl acetate (3x10ml).Organic layer with anhydrous sodium sulfate drying merges filters and vacuum concentration.Obtain 775mg (2.38mmol by silica gel cyclical chromatography purifying residue (adopting 10%-40% ethyl acetate/hexane gradient elution); 71%) 9-[(cyclopentyl) methyl] 5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone is brown foam.MS (ES) m/e 326 (M+1), 384 (M+AcO
-) C
20H
23NO
3Results of elemental analyses: calculated value: C, 73.82; H, 7.12; N, 4.30 measured values: C, 74.12; H, 7.21; N, the 4.45B.9-[(cyclopentyl) methyl]-4-hydroxy-5-methyl ester group carbazole
80 ℃ of heating 9-[(cyclopentyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone (730mg, 2.24mmol) and 2,3-two chloro-5,6-dicyano-1,4-benzoquinones (560mg, 2.47mmol) 20ml toluene solution 3 hours, reaction mixture is directly obtained 140mg (0.433mmol, 19%) 9-[(cyclopentyl by silica gel chromatography (using the methylene dichloride wash-out)) methyl]-4-hydroxy-5-methyl ester group carbazole, be yellow oil, it can slowly solidify.MS (ES) m/e 324 (M+1), 322 (M-1) C
20H
21NO
30.3H
2The results of elemental analyses of O: calculated value: C, 73.06; H, 6.62; N, 4.26 measured values: C, 73.19; H, 6.44; N, the 4.40C.9-[(cyclopentyl) methyl]-4-hydroxyl-5-formamyl carbazole
Handle the 9-[(cyclopentyl with the ammonia air-flow) methyl]-(110mg, 3ml THF 0.34mmol) and the solution of the dense ammonium hydroxide aqueous solution of 20ml also make it saturated to 4-hydroxy-5-methyl ester group carbazole.Add a cover and under agitation mixture heating up to 35 ℃ is shown starting raw material reaction finish (20 hours) up to tlc to reaction vessel.Evaporation THF also filters water layer.Solid with ether development gained obtains 50mg (0.162; 48%) title compound is light green-white solid, IR (KBr, cm
-1) 3416,3199,3126,1630,1599,1442,1262,778. ' FAB HRMS m/e.C
20H
21N
2O
2Calculated value be 309.1603, measured value is 309.1607 (M+1) D.[9-[(cyclopentyl) methyl]-5-formamyl carbazole-4-yl] the ethoxyacetic acid methyl esters
With methyl bromoacetate (0.018ml; 0.19mmol) handle the 9-[(cyclopentyl) methyl]-4-hydroxyl-5-formamyl carbazole (45mg, 0.146mmol) and Cs
2CO
3(120mg, 0.365mmol) the 2ml DMF solution of mixture stirring at room reaction 2 hours, are used ethyl acetate and water (10ml separately) dilution then.Extract with the saturated water layer of solid sodium chloride and with ethyl acetate (2x10ml), the organic layer that water (2x25ml) washing merges, the organic layer with anhydrous sodium sulfate drying merges filters and vacuum concentration.By flash chromatography on silica gel purifying residue crude product (with 0-100% ethyl acetate/hexane gradient elution), then obtain 26mg (0.0683mmol with ether/ethyl acetate development; 47%) title compound is brown solid.MS (ES) m/e 381 (M+1), 364 (M+H-NH
3), 439 (M+AcO
-) C
23H
26N
2O
40.1H
2The results of elemental analyses of O: calculated value: C, 69.13; H, 6.38; N, 7.33 measured values: C, 68.99; H, 6.39; N, the 7.41E.[9-[(cyclopentyl) methyl]-5-formamyl carbazole-4-yl] ethoxyacetic acid
Handle [9-[(cyclopentyl) methyl]-5-formamyl carbazole-4-yl with the 0.1ml 1N LiOH aqueous solution (0.1mmol)] ethoxyacetic acid methyl esters (20mg, 0.3ml THF 0.065mmol) and the slurries of 0.1ml methyl alcohol and in stirring at room mixture 2 hours.Remove organism with 0.2N hydrochloric acid acidizing reaction and vacuum.Filtering white precipitate and obtain 15mg (0.0409mmol from water layer with ether rinse; 63%) title acid compound is white powder.MS (ES) m/e 367 (M+1), 350 (M+H-NH
3), 365 (M-1) C
21H
22N
2O
40.3H
2The results of elemental analyses of O: calculated value: C, 67.84; H, 6.13; N, 7.53 measured values: C, 67.73; H, 5.97; N, 7.70
Embodiment 57 preparation [5-formamyl-9-(phenyl methyl)-2-(2-thienyl) carbazole-4-yl] ethoxyacetic acids
A. prepare 3-(2-bromo-3-methoxycarbonyl phenylamino)-5-(2-thienyl) hexamethylene-2-alkene-1-ketone
Press the method preparation of embodiment 17C, productive rate 59%.
1H-NMR (CDCl
3): δ 2.63 (dd, J=16.5,118.Hz, 1H), 2.78-2.96 (m, 3H), 3.71-3.80 (m, 1H), 3.94 (s, 3H), 5.61 (s, 1H), 6.23 (br s, 1H), 6.93 (d, J=3.5 Hz, 1H), 6.97-6.99 (m, 1H), 7.21 (d, J=5.2 Hz, 1H), 7.34 (br t, J=7.8 Hz, 1H), 7.55 (2H) .B. prepares 5-methoxycarbonyl-1 for d, J=7.8 Hz, 2-dihydro-2-(2-thienyl)-9H-carbazole-4 (3H)-ketone
Press the method preparation of embodiment 17D, productive rate 85%.
1H-NMR (CDCl
3): δ 2.73 (dd, J=16.3,11.8 Hz, 1H), 2.91 (dd, J=16.4,4.0 Hz, 1H), 3.03 (dd, J=16.6,10.8 Hz, 1H), 3.24 (dd, J=16.6,4.5 Hz, 1H), 3.75-3.78 (m, 1H), 4.03 (s, 3H), 6.88 (br s, 1H), 6.93-6.96 (m, 1H), 7.17 (d, J=5.0 Hz, 1H), 7.22-7.26 (m, 1H), 7.36 (d, J=7.4 Hz, 1H), 7.40 (d, J=8.0 Hz, 1H), 9.17 (br s, 1H) .C. prepares 5-methoxycarbonyl-1,2-dihydro-9-(phenyl methyl)-2-(2-thienyl) carbazole-4 (3H)-ketone
Press the method preparation of embodiment 17E, productive rate 88%.
1H-NMR (CDCl
3): δ 2.84 (dd, J=16.5,11.6 Hz, 1H), 2.97-3.10 (m, 2H), 3.34 (dd, J=16.5,4.5 Hz, 1H), 3.89-3.96 (m, 1H), 4.06 (s, 3H), 5.38 (s, 2H), 6.89-7.00 (m, 4H), 7.18 (d, J=5.3 Hz, 1H), (m, 6H) .D. prepares 5-methoxycarbonyl-4-hydroxyl-9-(phenyl methyl)-2-(2-thienyl) carbazole to 7.25-7.41
Press the method preparation of embodiment 17F method (b), productive rate 76%.
1H-NMR (CDCl
3): δ 4.11 (s, 3H), 5.55 (s; 2H), and 7.07-7.12 (m, 3H); 7.16 (s, 2H), 7.24-7.30 (m; 4H), and 7.37-7.42 (m, 2H); 7.56 (d, J=8.1 Hz, 1H); 8.01 (1H) .E. prepares 5-formamyl-4-hydroxyl-9-(phenyl methyl)-2-(2-thienyl) carbazole for d, J=7.6 Hz
Press the method preparation of embodiment 17G, productive rate 85%.
1H-NMR (DMSO-d
6): δ 5.73 (s, 2H), 6.87 (s; 1H), and 7.08-7.26 (m, 6H); 7.41-7.56 (m, 5H), 7.76 (br t; J=4.5 Hz, 1H), 8.39 (s; 1H), 8.83 (s, 1H); 10.76 (s, 1H) .F. preparation [5-formamyl-9-(phenyl methyl)-2-(2-thienyl) carbazole-4-yl] ethoxyacetic acid methyl esters
Press the method preparation of embodiment 17H, productive rate 92%.
1H-NMR (DMSO-d
6): δ 3.70 (s, 3H), 4.99 (s; 2H), 5.71 (s, 2H); 6.85 (s, 1H), 7.04 (d; J=7.2 Hz, 1H), 7.11-7.26 (m; 7H), 7.35 (br t, J=7.7 Hz; 1H), 7.50-7.57 (m, 5H) .G. preparation [5-formamyl-9-(phenyl methyl)-2-(2-thienyl) carbazole-4-yl] ethoxyacetic acid
Press the method preparation of embodiment 17I, productive rate 98%.
1H-??NMR(DMSO-d
6)：δ4.90(s，2H)，5.72(s，2H)，6.85(s，1H)，??7.04-7.26(m，7H)，7.33-7.38(m，2H)，7.50-7.59(m，4H)，??7.71(s，1H)，12.99(br?s，1H).
Embodiment 58[5-formamyl-9-(phenyl methyl)-2-[[(propylene-3-yl)] oxygen base] methyl] carbazole-4-yl] ethoxyacetic acid
A. prepare 5-methoxycarbonyl-1,2-dihydro-9-(phenyl methyl)-2-[[(propylene-3-yl) the oxygen base] methyl] carbazole-4-(3H)-ketone
Under nitrogen atmosphere with sodium hydride (63.4mg, 1.58mmol) be added to and contain embodiment 19C compound (480mg under stirring, 1.32mmol) and allyl bromide 98 (0.172ml, 1.98mmol) dry DMF (7ml) solution in, the solution of stirring at room gained 2 hours, before vacuum concentration with 2 these mixtures of acetic acid treatment.Obtain subhead compound (395mg, 74%) by silica gel chromatography purifying residue (with 30%-70% ethyl acetate/hexane gradient elution), be white solid.
IR (KBr) 1726,1654cm
-1 1H-NMR (CDCl
3): δ 2.40 (dd, J=16.5,11.1 Hz, 1H), 2.57-2.78 (m, 3H), 3.01-3.08 (m, 1H), 3.41 (dd, J=9.2,6.9Hz, 1H), 3.49 (dd, J=9.2,4.3 Hz, 1H), 3.95 (d, J=5.4Hz, 2H ,-CH
2O-), 4.04 (s, 3H ,-OCH
3), 5.14-5.27 (m, 2H ,=CH
2), 5.32 (s, 2H ,-NCH
2-), 5.80-5.92 (m, 1H ,-CH=), and 6.97-7.02 (m, 2H), 7.20-7.39 (m, 6H); ESIMS m/e 404 (M
++ 1); C
25H
25NO
4Results of elemental analyses: calculated value: C, 74.42; H, 6.25 measured values: C, 74.59; H, 6.07B. prepare 5-methoxycarbonyl-4-hydroxyl-9-(phenyl methyl)-2-[[(propylene-3-yl) the oxygen base] methyl] carbazole
Press the method preparation of embodiment 17F (b), productive rate 78%.
IR (CHCl
3) 3200 (br), 1687cm
-1 1H-NMR (CDCl
3): δ 4.04 (d, J=5.7 Hz, 2H ,-CH
2O-), 4.11 (s, 3H ,-OCH
3), 4.63 (s, 2H ,-OCH
2-), 5.15-5.31 (m, 2H ,=CH
2), 5.55 (s, 2H ,-NCH
2-), 5.88-6.02 (m, 1H ,-CH=), 6.81 (s, 1H), 6.99 (s, 1H), 7.05-7.09 (m, 2H), 7.22-7.30 (m, 3H), 7.40 (br t, J=8.0 Hz, 1H), 7.58 (d, J=8.0 Hz, 1H), 8.00 (d, J=8.0 Hz, 1H), 10.48 (s, 1H ,-OH); ESIMS m/e 402 (M
++ 1); C
25H
23NO
4Results of elemental analyses: calculated value: C, 74.80; H, 5.77 measured values: C, 75.08; H, 5.78C. prepare 5-formamyl-4-hydroxyl-9-(phenyl methyl)-2-[[(propylene-3-yl) the oxygen base] methyl] carbazole
Press the method preparation of embodiment 17G, productive rate 75%.IR (KBr) 3420,3203 (br), 3121,1632,1601cm
-1 1H-NMR (DMSO-d
6): δ 3.95 (d, J=5.3 Hz, 2H ,-CH
2O-), 4.50 (s, 2H ,-OCH
2-), 5.08-5.25 (m, 2H ,=CH
2), 5.65 (s, 2H ,-NCH
2-), 5.83-5.93 (m, 1H ,-CH=), 6.54 (s, 1H), 7.02-7.05 (m, 3H), 7.14-7.25 (m, 3H), 7.39-7.45 (m, 2H), 7.73-7.77 (m, 1H), 8.34 (s, 1H,-NH), 8.79 (s, 1H ,-NH), 10.53 (s, 1H ,-OH); ESIMS m/e 387 (M
++ 1); C
24H
22N
2O
3Results of elemental analyses: calculated value: C, 74.59; H, 5.74 measured values: C, 74.85; H, and the 5.93D. preparation [5-formamyl-9-(phenyl methyl)-2-[[(propylene-3-yl) the oxygen base] methyl] carbazole-4-yl] the ethoxyacetic acid methyl esters
Press the method preparation of embodiment 17H, productive rate 90%.IR (KBr) 3360,3167,1758,1639cm
-1 1H-NMR (CDCl
3): δ 3.83 (s, 3H ,-OCH
3), 4.00 (d, J=5.7 Hz, 2H ,-CH
2O-), 4.62 (s, 2H ,-OCH
2-), 4.91 (s, 2H ,-OCH
2-), 5.16-5.30 (m, 2H ,=CH
2), 5.52 (s, 2H ,-NCH
2-), 5.88-6.00 (m, 1H ,-CH=), 6.05 (br s, 2H ,-NH
2), 6.59 (s, 1H), 7.05 (s, 1H), 7.06-7.10 (m, 2H), 7.22-7.41 (m, 6H); ESIMS m/e 459 (M
++ 1) .E. preparation [5-formamyl-9-(phenyl methyl)-2-[[(propylene-3-yl) the oxygen base] methyl] carbazole-4-yl] ethoxyacetic acid
Press the method preparation of embodiment 17I, productive rate 89%.IR (KBr) 3453,3421,3332,3220,2580 (br), 1740,1724,1631 cm
-1 1H-NMR (DMSO-d
6): δ 3.95 (d, J=4.7 Hz, 2H ,-CH
2O-), 4.53 (s, 2H ,-OCH
2-), 4.79 (s, 2H ,-OCH
2-), 5.10-5.26 (m, 2H ,=CH
2), 5.64 (s, 2H ,-NCH
2-), 5.80-6.00 (m, 1H ,-CH=), 6.56 (s, 1H), 7.04-7.40 (m, 9H), 7.57 (d, J=8.1 Hz, 1H), 7.70 (s, 1H ,-NH), 12.94 (br s, 1H ,-CO
2H); ESIMS m/e 445 (M
++ 1); C
26H
24N
2O
5Results of elemental analyses: calculated value: C, 70.26; H, 5.44 measured values: C, 70.00; H, 5.42
Embodiment 59[5-formamyl-9-(phenyl methyl)-2-[(propoxy-) methyl] carbazole-4-yl] ethoxyacetic acid
A. preparation [5-formamyl-9-(phenyl methyl)-2-[(propoxy-) methyl] carbazole-4-yl] the ethoxyacetic acid methyl esters
In nitrogen atmosphere, platinum oxide (30mg) is added to contains example II D compound (120mg under stirring, 0.262mmol) THF (30ml) solution in, in hydrogen atmosphere, stirred the mixture 30 minutes, after filtering and concentrating, obtain subhead compound (117mg, 97%) by silica gel chromatography purifying residue (with 0-6% ethanol/methylene gradient elution), be white solid.
IR (KBr) 3364,3166,1758,1742,1642cm
-1 1H-NMR (CDCl
3): δ 0.91 (t, J=7.4 Hz, 3H ,-CH
3), 1.57-1.65 (m, 2H), 3.40 (t, J=6.6 Hz, 2H ,-OCH
2-), 3.83 (s, 3H ,-OCH
3), 4.60 (s, 2H ,-OCH
2-), 4.91 (s, 2H ,-OCH
2-), 5.52 (s, 2H ,-NCH
2-), 5.95 (br s, 1H ,-NH), 6.06 (br s, 1H ,-NH), 6.58 (s, 1H), 7.04 (s, 1H), 7.07-7.10 (m, 2H), 7.20-7.41 (m, 6H); ESIMS m/e 461 (M
++ 1) .B. preparation [5-formamyl-9-(phenyl methyl)-2-[(propoxy-) methyl] carbazole-4-yl] ethoxyacetic acid
Press the described method preparation of embodiment 17I, productive rate 99%IR (KBr) 3458,3413,3332,3232,2500 (br), 1716,1627cm
-1 1H-NMR (DMSO-d
6): δ 0.82 (t, J=7.3 Hz, 3H ,-CH
3), 1.45-1.53 (m, 2H), 3.33 (t, J=6.3 Hz, 2H ,-OCH
2-), 4.51 (s, 2H ,-CH
2O-), 4.78 (s, 2H ,-OCH
2-), 5.64 (s, 2H ,-NCH
2-), 6.54 (s, 1H), 7.03-7.39 (m, 9H), 7.57 (d, J=8.2 Hz, 1H), 7.70 (s, 1H ,-NH), 12.93 (s, 1H ,-CO
2H); ESIMS m/e 447 (M
++ 1); C
26H
26N
2O
5Results of elemental analyses: calculated value: C, 69.94; H, 5.87 measured values; C, 70.00; H, 5.88
Embodiment 60 preparation 9-benzyl-7-methoxyl group-5-((formamido group methyl) oxygen base)-1,2,3,4-tetrahydro carbazole-4-methane amide
To 195mg (0.5mmol) 9-benzyl-7-methoxyl group-5-cyano group methoxyl group-1,2,3, add 34mg (0.1mmol) tetrabutyl ammonium sulfate in the 3ml dichloromethane solution of 4-tetrahydro carbazole-4-methane amide.After being cooled to 0 ℃, add 0.25ml 30%H
2O
2With 3ml 20% sodium hydroxide, make reaction be warmed up to room temperature and stirred 18 hours.With methylene dichloride diluted mixture thing, wash and use the salt water washing with water, use dried over sodium sulfate, and vacuum-evaporation.By silica gel chromatography purifying residue, the Virahol/dichloromethane gradient wash-out with 2-10% obtains title product (36.7mg, 19%).Use the methanol crystallization analytic sample.MS (ES+) 408C
23H
25N
3O
4Results of elemental analyses: calculated value: C67.80; H6.18; N10.31 theoretical value: C67.91; H6.17; N10.44
Embodiment 61 preparation 9-benzyl-7-methoxyl group-5-cyano group methoxyl group-carbazole-4-methane amides
9-benzyl-5-hydroxyl-7-methoxyl group carbazole-4-methane amide (0.75g under stirring, 2.17mmol) DMF (76ml) and THF (16ml) solution in add 60% sodium hydride (0.11g, 2.71mmol), add after 15 minutes bromoacetonitrile (0.20ml, 2.93mmol) and stirring reaction 4 hours.Use the ethyl acetate diluting reaction, water is used saline water extraction then, and dry (sodium sulfate) by the silica gel chromatography purifying, adopts methylene dichloride-ethyl acetate-methyl alcohol gradient elution, obtains title compound (0.52g, 63%).MS (ES+) 386C
23H
19N
3O
3Results of elemental analyses: calculated value: C71.68; H4.97; N10.90 theoretical value: C71.67; H4.72; N10.65
Embodiment 62 preparation 9-benzyl-7-methoxyl group-5-((1H-tetrazolium-5-base-methyl) oxygen base)-carbazole-4-methane amides
At 95 ℃ 0.20g (0.52mmol) 9-benzyl-7-methoxyl group-5-cyano group methoxyl group-carbazole-4-methane amide and 2.2ml tri-n-butyl tin hydride were heated 3.5 hours, reaction mixture is added in the mixture of 56ml acetonitrile, 11ml tetrahydrofuran (THF) and 21ml acetate then, and stirred 2 hours.With hexane extraction mixture 4 times and vacuum-evaporation residue.By silica gel chromatography purifying residue, adopt methylene chloride-methanol, 1% acetate/ethyl acetate gradient elution then.Obtain title compound (0.047g, 21%) with acetone and hexane crystallization.MS (ES+) 412,429C
23H
24N
6O
3Results of elemental analyses: calculated value: C64.48; H4.71; N19.61 theoretical value: C64.58; H4.67; N19.68
Embodiment the 63rd preparation 9-benzyl-7-methoxyl group-5-((formamido group methyl) oxygen base)-carbazole-4-methane amide
In the 6ml dichloromethane solution of 200mg (0.52mmol) 9-benzyl-7-methoxyl group-5-cyano group methoxyl group-carbazole-4-methane amide, add 35mg (0.1mmol) tetrabutyl ammonium sulfate.After being cooled to 0 ℃, add 0.26ml30%H
2O
2With 6ml 20% sodium hydroxide, make reaction be warmed up to room temperature and stirred 18 hours.With methylene dichloride and methyl alcohol diluted mixture thing, wash and use the salt water washing with water, use dried over sodium sulfate, and vacuum-evaporation.By silica gel chromatography purifying residue, use the dichloromethane-ethanol gradient elution, use methanol crystallization, obtain title compound (22.5mg, 11%).MS (FD) 403C
23H
21N
3O
4Results of elemental analyses: calculated value: C 68.47; H 5.25; N 10.42 theoretical values: C 68.65; H 4.99; N 10.40
Embodiment 64 preparation [9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acids
A.9-benzyl-4-carboxyl-5-methoxyl group-1,2,3,4-tetrahydro carbazole, ethyl ester
Handle 1.50g (4.02mmol) 9-benzyl-4-carboxyl-8-chloro-5-methoxyl group-1,2,3 with 0.24g 5% Pd-C, the 25ml ethanolic soln of 4-tetrahydro carbazole ethyl ester and 0.45g (4.40mmol) triethylamine, and in the mixture of 60psi hydrogenation gained 16 hours.Filtering reaction and vacuum concentration obtain the 1.40g brown solid.
1H NMR (CDCl
3) δ 7.30-7.19 (m, 3H), 7.03-6.95 (m, 3H), 6.80 (d, 1H, J=8.1 Hz), 6.44 (d, 1H, J=7.7 Hz), (5.22 d, 2H, J=5.9 Hz), 4.22-4.11 (m, 3H), 3.82 (s, 3H), 2.75-2.64 (m, 1H), and 2.59-2.48 (m, 1H), 2.11-1.64 (m, 4H) and 1.25 (t, 3H, J=7.0 Hz) .IR (CHCl
3) 2959,1725,1499,1453,1260,1178,1128cm-1; C
23H
25NO
3Results of elemental analyses: calculated value: 363.1836 measured values: 363.1834B.9-benzyl-4-formamyl-5-hydroxyl-1,2,3,4-tetrahydro carbazole
At 0 ℃ with 22.40ml (22.40mmol; The 1M dichloromethane solution) boron tribromide is handled 1.00g (2.80mmol) 9-benzyl-4-carboxyl-5-methoxyl group-1,2,3, the 15ml dichloromethane solution of 4-tetrahydro carbazole ethyl ester.Remove cooling bath and stirring reaction and show that up to tlc analysis (10% ethyl acetate/hexane) starting raw material reacts finish (1.5 hours).Reaction is cooled to 0 ℃ also with 5.0ml methyl alcohol stopped reaction, at stirring at room mixture 18 hours and vacuum concentration.The dark oil thing of gained is dissolved in the 200ml methylene dichloride, water (100ml) and saturated sodium bicarbonate aqueous solution (100ml) washing soln, vacuum evaporating solvent obtains 700mg dark oil thing.Obtain 400mg 9-benzyl-4-carboxyl-5-hydroxyl-1,2,3 by cyclical chromatography (10% ethyl acetate/hexane) purifying, 4-tetrahydro carbazole ethyl ester is directly used in next step reaction with it.
The phenol that obtains is dissolved among the 40ml THF and handles gained solution, add a cover and the mixture of vigorous stirring gained 13 days to reaction vessel with 10ml ammonium hydroxide.To extract mixture in the reaction mixture impouring water and with ethyl acetate (3x150ml).The organic layer that dry (sodium sulfate) merges filters and vacuum concentration obtains the brown foam of 300mg.Obtain 9-benzyl-4-formamyl-5-hydroxyl-1,2,3,4-tetrahydro carbazole by cyclical chromatography purifying (3% ethanol/methylene) 50mg starting phenol and 80mg (0.03mmol, 22%).
1H NMR (CDCl
3) δ 7.33-7.24 (m, 3H), 7.06-6.97 (m, 3H), 6.81 (d, 1H, J=8.1 Hz), 6.56 (d, 1H, J=7.5 Hz), (5.22 d, 2H, J=2.2 Hz), and 4.20-4.15 (m, 1H), 2.78-2.67 (m, 1H), 2.63-2.51 (m, 1H), 2.35-2.27 (m, 1H), (m 3H), does not measure phenol proton IR (CHCl3) 3007,1667 to and 2.09-1.91,1586,1567,1496,1266cm-1; C
20H
21N
2O
2Results of elemental analyses: calculated value: 321.1603 measured values: 321.1607C.[9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] the ethoxyacetic acid methyl esters
With 61mg (0.30mmol) cesium carbonate; then handle 80mg (0.25mmol) 9-benzyl-4-formamyl-5-hydroxyl-1 with the methyl bromoacetate of 26mg (0.30mmol); 2; 3; the 2.5ml DMF solution of 4-tetrahydro carbazole shows starting raw material reaction finish (2 hours) at the mixture of stirring at room gained up to tlc.Water (10ml) diluting reaction also uses ethyl acetate (3x10ml) to extract.The organic layer that water (3x20ml) washing merges is used dried over sodium sulfate, filters and vacuum concentration.By cyclical chromatography purifying residue (SiO
22.5% ethanol/methylene) obtains 50mg (0.13mmol, 51%) [9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid methyl esters, be oily matter.
1H NMR (CDCl
3) δ 7.33-7.21 (m, 3H), 7.05-6.98 (m, 3H), 6.98 (d, 1H, J=7.4 Hz), 6.46 (br s, 1H), 6.37 (d, 1H, J=7.7 Hz), 5.52 (br s, 1H), 5.23 (d, 1H, J=4.9 Hz) 4.79-4.70 (m, 2H), 4.20-4.15 (m, 1H), 3.81 (s, 3H), 2.79-2.69 (m, 1H), 2.63-2.49 (m, 1H), 2.43-2.35 (m, 1H), and 2.25-2.09 (m, 1H), and 1.99-1.78 (m, 2H) .IR (CHCl
3, cm
-1) 1759,1670,1497,1453,1440, and 1132.MS (ES) m/e 393 (M+1) .C
23H
24N
2O
4Results of elemental analyses: calculated value: C, 70.39; H, 6.16; N, 7.14 measured values; C, 70.29; H, 6.31; N, 7.08D.[9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid
Handle 30mg (0.076mmol) [9-benzyl-4-formamyl-1 with 0.2ml 1N LiOH (0.2mmol) aqueous solution; 2; 3; 4-tetrahydro carbazole-5-yl] 1.0mlTHF of ethoxyacetic acid methyl esters and the solution of 1.0ml methyl alcohol; stirred the mixture 18 hours, and added other 0.2ml 1N LiOH (0.2mmol) aqueous solution and continue and stir.1 hour final vacuum enriched mixture.Residue is dissolved in the 2.0ml water, and with 0.2N aqueous hydrochloric acid souring soln.Cross filter solid and drying and obtain 25mg[9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid, be white solid.
1H NMR (DMSO-d6) δ 7.36-7.12 (m, 5H), 7.05-6.83 (m, 5H), 6.71 (br s, 1H), 6.35 (d, 1H, J=7.6 Hz), 5.27 (s, 2H), 4.64 (s, 2H), and 3.93-3.84 (m, 2H), 2.75-2.64 (m, 1H), and 2.16-1.95 (m, 2H), 1.81-1.64 (m, 2H) and proton peak IR (KBr, a cm between 2.58-2.40, being covered by the water peak
-1) 3435,2936,1722,1644,1586,1566,1495,1451,1354,1227,1134,730,716, and 698.MS (ES) m/e 377 (M-1) and 379 (M+1) .C
22H
22N
2O
4Results of elemental analyses: calculated value: C, 69.83; H, 5.86; N, 7.40 measured values: C, 70.11; H, 5.76; N, 7.12
Compound as herein described mainly is by direct inhibition people sPLA
2Show useful therapeutic activity, rather than work, neither work as the antagonist of other promoting agent (as 5-lipoxygenase, cyclooxygenase etc.) after the arachidonic acid in the arachidonic acid cascade as arachidonic antagonist.
The present invention suppresses sPLA
2The method that the lipid acid of mediation discharges comprises: make sPLA
2Contact with formula (I) compound or its salt of treatment significant quantity.
The compounds of this invention can be used for alleviating in the methods of treatment of pathological symptoms such as septic shock, adult respiratory distress syndrome, pancreatitis, wound, bronchial asthma, allergic rhinitis and rheumatoid arthritis of Mammals (for example human), and this method comprises formula (I) compound to administration treatment significant quantity." treatment significant quantity " is meant and is enough to suppress sPLA
2Thereby the lipid acid of mediation discharges the amount that is enough to suppress or prevent arachidonic acid cascade and its deleterious product.Suppress sPLA
2The therapeutic dose of required The compounds of this invention is by sampling of bodily fluid and adopt ordinary method to analyze wherein sPLA
2Content is easy to determine.
Make a general survey of this paper, the human or animal that will treat is referred to as " Mammals ", and be to be understood that most preferred main body is the people.But it should be noted that the research to non--human animal's central nervous system rough sledding has been not only beginning, so that some this treatment tries out.Therefore, the application of The compounds of this invention in non--human animal finished.Be to be understood that dosage range to other animal is different from the dosage range to human administration certainly fully, therefore dosage described here should recomputate.For example, a doggie is 1/10 of a common human body size, certainly will be with much smaller dosage.Significant quantity to specifically non--human animal is to determine the mode of the very familiar this decision dosage of animal doctor by following same mode to the mankind.
As previously mentioned, The compounds of this invention can be used for suppressing sPLA
2The release of the lipid acid (as arachidonic acid) of mediation.Term " inhibition " is meant that The compounds of this invention can stop or treat upward obviously reduction sPLA
2The release of the lipid acid that causes." pharmaceutically acceptable " is meant that carrier, thinner or vehicle must be compatible with other composition of prescription and be harmless to the receptor.
Generally speaking, The compounds of this invention is preferably taken and can be taken by single unitary dose can produce the dosage that beneficial effect do not cause any serious side effects again usually, perhaps if desired, dosage can be divided into suitable sub-dosage, the time suitable among one day takes.
Use the concrete dosage of The compounds of this invention to depend on the concrete situation of relevant case certainly in order to obtain treatment or preventive effect, the approach that comprises for example administration, age, the body weight of individual patient and reaction, state and severity patient symptom when being treated.Typical per daily dose comprises that the non-toxic dosage level is the The compounds of this invention of about 0.01mg/kg to about 50mg/kg body weight.
Preferred drug substances is the form with unitary dose.This unit dosage form can be capsule or tablet itself, or the capsule of suitable number or tablet.The amount of activeconstituents can change in the about 1000mg scope of about 0.1-or under the more situation of consumption or adjust according to relevant specifically treatment situation in units dosage composition.Should understand according to patient's age and situation and can do conventional change dosage.Dosage also depends on the approach of taking.
The slow development of " chronic " state Shi Evilization state and long-term continuing.Like this, begin treatment and in the whole course of disease, will carry out continued treatment when this disease is diagnosed." acute " state is meant that disease enters remission stage subsequently in the short-term fast development.Under acute situations, be when symptom occurring, to take compound and behind transference cure, cut out.
Shock, bronchial asthma, allergic rhinitis and rheumatoid arthritis that pancreatitis, wound cause can be acute or chronic outbreak.Therefore, these treatment of diseases are comprised acute and chronic two kinds of dual modes.On the other hand, when being diagnosed as septic shock and adult respiratory distress syndrome, by the acute situations treatment.
Compound can be used by number of ways, comprise oral, smoke substance, rectum, transdermal, subcutaneous, vein, intramuscular and intranasal administration.
Pharmaceutical preparation of the present invention can combine (for example mixing) preparation by the The compounds of this invention that will treat significant quantity with medicine acceptable carrier or thinner.Can prepare pharmaceutical preparation of the present invention with batching that be easy to get by known method employing is that know.
When preparation composition of the present invention, usually activeconstituents is mixed with carrier, or dilute activeconstituents, or activeconstituents is included in the carrier (form of carrier can be capsule, sachet, paper or other container) with carrier.When carrier during as thinner, it can be solid, semisolid or liquid substance as carrier; And when carrier during as vehicle, it can be tablet, pill, pulvis, lozenge, elixir, suspension, emulsion, solution, syrup, smoke substance (for solid or in liquid medium) or ointment; For example wherein contain the active compound of 10% weight at the most.Preferably before using, The compounds of this invention is made dosage form.
Can adopt any suitable carriers useful in preparing drug formulations known in the art.In such preparation, carrier can be solid, liquid or solid and mixtures of liquids.The preparation of solid form comprises pulvis, tablet or capsule.Solid carrier be can be simultaneously as one or more materials of seasonings, lubricant, solubilizing agent, suspension agent, tackiness agent, tablet disintegrant and preparation capsule raw material.
Oral tablet contains suitable vehicle (as lime carbonate, yellow soda ash, lactose, calcium phosphate) and disintegrating agent (as corn, starch or alginic acid), and/or tackiness agent (as gelatin or gum arabic), and lubricant (as Magnesium Stearate, stearic acid or talcum powder).
In pulvis, carrier is the solid finely divided with finely divided activeconstituents blended.In tablet, activeconstituents is mixed and is pressed into the form and the size of needs with the carrier with suitable bond properties with suitable ratio.Pulvis and tablet preferably contain the new compound of the present invention of about 99% weight of the 1%-that has an appointment as activeconstituents.Suitable solid carrier is magnesiumcarbonate, Magnesium Stearate, talcum, sugar, lactose, pectin, dextrin, starch, gelatin, tragakanta methylcellulose gum, Xylo-Mucine low melt point paraffin and theobroma oil.
Sterile liquid formulations comprises suspension, emulsion, syrup and elixir.
Activeconstituents is dissolved in or is suspended in pharmaceutically acceptable carrier (as sterilized water, aseptic organic solvent or the mixture of the two).Usually activeconstituents can be dissolved in the appropriate organic solvent (as aqueous solution of propylene glycol).Other composition can be prepared by finely divided activeconstituents is dispersed in starch or the sodium carboxymethyl cellulose solution or is dispersed in the suitable oil.
Following pharmaceutical preparation 1-8 be illustrative be not to limit the scope of the invention in any manner." activeconstituents " is meant formula (III) compound or pharmaceutically acceptable salt thereof, solvate or prodrug.
Preparation 1
Adopt following batching to prepare hard gelatin capsule:
Amount
(mg/ capsule) embodiment 5 compounds 250 starch, dry 200 Magnesium Stearates 10 are 460mg altogether
Preparation 2
Adopt following batching to prepare tablet:
Amount
(mg/ tablet) embodiment 10 compounds 250 Microcrystalline Celluloses 400 silicon-dioxide, smoked back 10 stearic acid 5 are 665mg altogether
The tablet that said components is mixed and is pressed into every heavy 665mg.
Preparation 3
Adopt following component to prepare smoke substance solution:
Weight embodiment 15 compounds 0.25 ethanol 25.75 propelling agents 22 (chlorodifluoromethane) 74.00 totally 100
Active compound is mixed with ethanol and mixture is added in a part of propelling agent 22, be cooled to-30 ℃ and transfer in the tamping unit.Then required amount is installed in the stainless steel vessel and and dilute with remaining propelling agent.Be equipped with valve part to container then.
Preparation 4
Preparation as described below contains the tablet of 60mg active component: embodiment 25 compound 60mg starch 45mg microcrystalline cellulose 35mg PVP (being 10% aqueous solution) 4mg sodium carboxymethyl starch 4.5mg dolomol 0.5mg talcum powder 1mg 150mg altogether separately
With activeconstituents, starch and Mierocrystalline cellulose are by No.45 order U.S. sieve and thorough mixing.The powder mixes that will contain the aqueous solution and the gained of Polyvinylpyrolidone (PVP) makes mixture pass through No.14 order U.S. sieve then.At the particle of 50 ℃ of dry gained and by No.18 order U.S. sieve.Then will be in advance by the sodium starch glycolate of No.60 order U.S. sieve, Magnesium Stearate and talcum powder are added in the particle, mix to be placed on the tablet that the tabletting machine compressing tablet obtains every heavy 150mg.
Preparation 5
Every of preparation as described below contains the capsule of 80mg activeconstituents: embodiment 30 compound 80mg starch 59mg Microcrystalline Cellulose Mierocrystalline cellulose 59mg Magnesium Stearate 2mg 200mg altogether
Activeconstituents, Mierocrystalline cellulose, starch and Magnesium Stearate are sieved by No.45 order U.S., and be filled in the hard gelatin capsule with the amount of 200mg.
Preparation 6
Every of preparation as described below contains the suppository of 225mg activeconstituents: embodiment 35 compound 225mg saturated fatty acid glycerides 2, and 000mg totally 2,225mg
With activeconstituents by No.60 order U.S sieve and be suspended in advance in the saturated fatty acid glyceride with necessary minimal amount of heat thawing.Then mixture to be poured into minimum volume be in the 2g suppository mould and make it cooling.
Preparation 7
The every 5ml dosage of preparation as described below contain the 50mg activeconstituents suspension: embodiment 40 compound 50mg Xylo-Mucine 50mg syrup 1.25ml benzoic acid solution 0.10ml seasonings amount of colorant add purified water in right amount to total amount 5ml
Activeconstituents mixed uniformly by No.45 order U.S sieve and with Xylo-Mucine and syrup stuck with paste.Under agitation benzoic acid solution, seasonings and tinting material are diluted and adding with a part of water.Add enough water then and obtain required volume.
Preparation 8
Preparation intravenous formulations as described below: embodiment compound 100mg isotonic saline solution 1,000ml
The speed of pressing usually 1ml/ minute is given the solution of patient's intravenous administration said components.
Experimental example 1
Adopt people's excretory phospholipase A that following staining test method is determined and assessment is recombinated
2Inhibitor.Test described here is through improving a large amount of screenings that are adapted to adopt 96 hole microtitration flat boards.Explanation to this test can be found " Analysis of Human Synovial Fluid Phospholipase A hereinafter
2On Short ChainPhosphatidylcholine-Mixed Micelles:Development of a Spectrophotometric AssaySuitable for a Microtiterplate Reader "; by Laure J.Reynolds; Lori L.Hughs; and Edward A Dennis shows; Analytical Biochemistry; 204, pp.190-197,1992.(above-mentioned disclosure is incorporated herein as a reference) reagent: reaction buffer-
CaCl
2.2H
2O(1.47g/L)
KCl(7.455g/L)
Bovine serum albumin (FAF) (1g/L)
(Sigma A-7030, Sigma Chemical Co.st.Louis MO, the product of USA)
TRIS?HCl(3.94g/L)
PH7.5 (regulating) with sodium hydroxide.Enzyme buffer liquid-
0.05NaOAc.3H
2O，PH4.5
0.2NaCl
With acetate PH is transferred to 4.5.DTNB-5,5 '-dithio two-2-nitrobenzoic acid racemize two oenanthyl sulfo--PC
Racemize 1,2-two (oenanthyl sulfo-)-1,2-dideoxy-sn-glyceryl-3-phosphorylcholine
TRITON X-100
TM, in reaction buffer, press the 6.249mg/ml preparation, be equivalent to 10 μ M.
TRITON X-100
TM, be by Pierce Chemical Company, 3747 N.Meridian Road, Rockford, the polyoxyethylene nonionic detergent that Illinois 61101 provides.Reaction mixture-
With the volumetric racemize that in chloroform, provides two oenanthyl sulfo--PC (concentration is 100mg/ml) drying, and be dissolved in 10mmol TRITON X-100 again
TMIn the nonionic detergent aqueous solution.In solution, add reaction buffer, add DTNB then and obtain reaction mixture.
The reaction mixture that obtains like this contains 1mM two oenanthyl sulfo--PC substrate, 0.29mm TRITON X-100 in the PH7.5 aqueous buffer solution
TMWashing composition and 0.12mm DTNB.Experimental technique:
1. in all holes, add the 0.2ml reaction mixture;
2. in suitable hole, add 10 μ l test compounds (or only being the solvent blank group), mixed 20 seconds;
3. in suitable hole, add 50 nanogram sPLA
2(10 μ l);
4. 40 ℃ of culture plates 30 minutes;
5. measure the optical density of 405 nanometers by automatic plate reader.
All compounds are tested in triplicate.Usually compound is tested with ultimate density 5 μ g/ml.When 405 nanometers are measured, when with the control reaction (group) that does not have to suppress when comparing when compound exhibits 40% or higher inhibiting rate, think that compound is active.Inhibition taken place in the 405 nanometers proof that do not develop the color.If the activated compound of preliminary discovery is tested once more to determine their activity and active sufficiently high words, is measured its IC
50Value.Common IC
50Value (stating table 1 as follows) is to make the reaction ultimate density measure under the situation of 45 μ g/ml to 0.35 μ g/ml 2 times of test compound serial dilutions.Most of effective inhibitors need the dilution of more multiples.In all cases, all contain the percent inhibition of the enzyme reaction of inhibitor with respect to the control reaction that does not have to suppress in 405 nanometers mensuration.The triplicate every duplicate samples of titration, and with average back mapping of the end value of gained and calculating IC
50Value.Can calculate IC by drawing logarithm concentration to the inhibiting rate in the 10-90% scope
50Value.
In experimental example 1, test The compounds of this invention, find that it is effective that this compound is lower than 100 μ M in concentration.
Experimental example 2 methods:
To kill male Hartley be cavy (500-700g) and take out complete heart and lung by neck dislocation method, places inflation (95% oxygen: Kreb damping fluid 5% carbonic acid gas).(separate back pleura bar (4 * 1 * 25cm) 8 * 4 * 25cm) otch from the complete parenchyma part parallel with the lower lobe outer ledge.Two that obtain from the single lobe of the lung at each terminal tighten and represented single tissue sample adjacent back pleura bars, and be respectively fixed on the metallic support rod.One rod is connected Grass force-displacement transverter (model FTO3C is Grass Medical Instrument Co., Quincy, MA, the product of USA).Show the variation of isometric tension by monitor and heat registering instrument (Modular Instrument, Malvem, the product of PA).Place the 10ml that maintains 37 ℃ to add the tissue bath of cover in all tissues.This tissue bath is continued to inflate and is wherein contained the improved Kreb solution (mmol) that comprises following component: NaCl, 118.2; KCl, 4.6; CaCl
2.2H
2O, 2.5; MgSO
4.7H
2O, 1.2; NaHCO
3, 24.8; KH
2PO
4, 1.0 and glucose, 1.0.The pleura bar that obtains from the opposite lobe of the lung is used for pair test.The original date that obtains from tension force/response curve proves that the resting tension of 800mg is an ideal.Owing to bathe the fluid periodical change, should make structural equation 45 minutes.Cumulative concentration-response curve:
Stimulate original structure 3 vigor and acquisition homogeneous responses with KCl (40mM) with test organization.After the maximum reaction of record to KCl, the washing tissue also makes it to get back to baseline before stimulating next time.Cumulative concentration-response curve is obtained by the pleura bar, is by increasing agonist (sPLA in the tissue bath with half-log10 increment
2) concentration, (Ref.1 supra) obtains the concentration that keeps the front simultaneously in order to contact with tissue.After reaching the contraction platform that is caused by front concentration, the concentration of agonist increases.Organize from each and all to obtain a concentration-response curve.Minimum in order to drop to from the difference between the tissue of different animals acquisitions, contractile response is to stimulate the percentage ratio of the maximum reaction that obtains to represent with last KCl.When studying multiple medicine to sPLA
2During the influencing of contractive effect, at beginning sPLA
2Preceding 30 minutes of concentration-response curve is added compound and their carriers separately.Statistical analysis:
Compile the data of different tests and (percentage ratio of mean value ± S.E.) is represented with maximum KCl reaction.In order to estimate drug-induced moving to right, adopt and Waud (1976) in the concentration-response curve, Equation 26, p.163, (Ref.2) described similar statistics non--the linear model method analyzes curve.This model comprises 4 parameters: the maximum tissue reaction, suppose for each curve it should is identical; The ED of control curve
50, i.e. slope of a curve; And PA
2Need to increase by 2 times of antagonist concentration of agonist with the acquisition equivalent responses.Adopt and Waud (1976), Equation 26, p.164, (Ref.2) described similar statistics non--the linear model method is decided to be 1 with the Schild gradient.The Schild gradient is that 1 this model of expression is consistent with the competitive antagonist of supposition; Therefore, PA
2Can be interpreted as K
B, i.e. the dissociation constant of inhibitor.
In order to assess the inhibition to the maximum reaction of medicine-initiation, under the situation that does not have medicine and have medicine to exist, measure sPLA
2Reaction (10 μ g/ml), and calculate and respectively organize right inhibition per-cent.In following table 2, provided and suppressed active representational embodiment.
Ref.1-Van, J.M.: integral dose-response curve II.. obtains to separate the technology of organ dose-response curve and to the assessment of drug parameters.Arch.Int.Pharmacodyn.Ther.，143：299-330，1963。
Ref.2-Waud, D.: to the analysis of dose-response relationship.See Advances in general and CellularPharmacology eds Narahashi, Bianchi 1:145-178,1976.
In experimental example 2, measure The compounds of this invention, find that they are lower than 20 μ M in concentration is effective.
Experimental example 3
SPLA
2Transgenic mice test raw material and method
In these trials the mouse of Cai Yonging be grow up, the age 6-8 month, stimulate with zinc sulfate, subsystem 2608 narrows
aTransgenic mice (Fox etc., 1996).This transgenic mice that is is expressed human sPLA in liver and other tissue
2, and when carrying out maximal stimulation (Fox etc., 1996), in its circulation, can reach human sPLA usually with zinc sulfate
2Level is about 173 ± 10ng/ml.The mouse of under the condition of fixed humidity and temperature and free pickuping food and water, raising in cages.The illumination of Animal House keeps illumination/12 hour dark circulation in 12 hours, and all tests all are to be to carry out in photostage in morning in the same time.
To vein test, compound or carrier with IV medicine group by the tail vein by volume 0.15ml use.Carrier is made up of 1-5% methyl-sulphoxide soluble in water, 1-5% ethanol and 10-30% Liquid Macrogol.These component concentrations are adjusted according to the solubleness of compound.Before taking medicine or carrier and take after 30 minutes, 2 hours and 4 hours with bloodletting behind the mouse socket of the eye.Each dosage uses 3 to 6 mouse down.Adopt 3mM Sodium desoxycholate and 1mM 1-palmitoyl-2-oleoyl-sn-glyceryl-3-phosphorylcholine to measure sPLA in the serum by improved phosphatidyl choline/deoxidation choline mixed molecules group test (Fox, etc., 1996, Schadlich etc., 1987)
2Catalytic activity.
To oral test, compound is dissolved in the aqueous solution of 1-5% ethanol/10-30% Liquid Macrogol or is suspended in the aqueous solution of 5% dextrose and passes through oral gavage.Prepare serum and measure sPLA as mentioned above by blood behind the socket of the eye
2Catalytic activity.Reference
Fox, N., M.Song, J.Schrementi, J.D.Sharp, D.L.White, D.W.Snyder, L.W.Hartley, D.G.Carlson, N.J.Bach, R.D.Dillard, S.E.Draheim, J.L.Bobbitt, L.Fisher and E.D.Mihelich.1996
Eur.J.Pharmacol.308:195.Schadlich, H.R., M.Buchler, and H.G.Beger, 1987, J.Clin.Chem.Clin
Biochem.25，505。
Measure The compounds of this invention in experimental example 3, discovery is effective.
Here just by some concrete example explanation the present invention, be not (protection) scope with the appended claims of the present invention in these specific embodiment restriction back.
Claims (44)
1. formula (I) compound or its pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or salt:
Wherein: Z is a cyclohexenyl, or phenyl, R
20Be selected from group (a), (b) and (c), wherein:
(a) be-(C
5-C
20) alkyl ,-(C
5-C
20) alkenyl ,-(C
5-C
20) alkynyl group, carbocylic radical, or heterocyclic radical, or
(b) be by group among one or more independent (a) that substituting group replaced of not interfering with each other that select; Or
(c) be group-(L)-R
80Wherein, (L)-for containing 1-12 divalent linker that is selected from carbon, hydrogen, oxygen, nitrogen and sulphur atom; Wherein-(L)-and the combination of middle atom is selected from (i) and has only carbon and hydrogen, (ii) has only a sulphur, (iii) has only an oxygen, (iv) has only one or two nitrogen and hydrogen, and (v) have only carbon, hydrogen and a sulphur and (vi) have only carbon, hydrogen and oxygen; And R wherein
80For being selected from (a) or group (b); R
21Be the substituting group that does not interfere with each other, wherein f is 1-3; R
1For-NHNH
2,-NH
2, or-CONH
2R
2 'Be selected from group-OH and-O (CH
2)
tR
5 ', wherein
R
5 'Be H ,-CN ,-NH
2,-CONH
2,-CONR
9R
10,-NHSO
2R
15-CONHSO
2R
15, R wherein
15For-(C
1-C
6) alkyl or-CF
3Phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that replaces of alkyl; With-(L
a)-(acidic-group), wherein-(L
a)-for the acid with the basic length of 1-7 acid connection connects base, and t is 1-5; R
3 'Be selected from the substituting group that does not interfere with each other, carbocylic radical, the carbocylic radical that substituting group replaced that is not interfered with each other, heterocyclic radical and the heterocyclic radical that substituting group replaced that is not interfered with each other.
2. formula (II) compound or its pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or salt:
Wherein: Z is a cyclohexenyl, or phenyl, R
21Be the substituting group that does not interfere with each other; R
1For-NHNH
2Or-NH
2R
2Be selected from group-OH and-O (CH
2)
mR
5, wherein
R
5Be H ,-CO
2H ,-CONH
2,-CO
2(C
1-C
4Alkyl);
R wherein
6And R
7Be independently of one another-OH or-O (C
1-C
4) alkyl;-SO
3H ,-SO
3(C1-C4 alkyl), tetrazyl ,-CN ,-NH
2,-NHSO
2R
15-CONHSO
2R
15, R wherein
15For-(C
1-C
6) alkyl or-CF
3Phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that alkyl replaces, wherein m is 1-3; R
3Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-CONH
2,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be independently-(C
1-C
4) alkyl, or-phenyl (C
1-C
4) alkyl, and n is 1-8; And R
4Be H ,-(C
5-C
14) alkyl ,-(C
3-C
14) cycloalkyl, pyridyl, phenyl or selected :-(C from the following phenyl that substituting group replaced
1-C
6) alkyl, halogen ,-CF
3,-OCF
3,-(C
1-C
4) alkoxyl group ,-CN ,-(C
1-C
4) alkylthio, phenyl (C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, phenyl, phenoxy group or naphthyl.
3. the formula of claim 2 (II) compound, wherein
R
1For-NH
2With
Z is a phenyl.
4. each compound, wherein R in the claim 2 or 3
5Be H, NH
2,-CONH
2,-SO
3H ,-SO
3(C
1-C
4) alkyl, tetrazyl ,-CN ,-NH
2,-NHSO
2R
15-CONHSO
2R
15R wherein
15Be (C
1-C
6) alkyl ,-CF
3, phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that replaces of alkyl.
5. each described formula (II) compound, wherein R among the claim 2-4
3Be halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
4) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl or-(C
1-C
6) hydroxyalkyl.
6. each described formula (II) compound, wherein R among the claim 2-5
4Be pyridyl, by (C
5-C
6) alkyl ,-CF
3,-OCF
3,-CN ,-(C
1-C
4) alkyl phenyl, the phenyl of phenoxy group or naphthyl substituted.
7. each described formula (II) compound, wherein R among the claim 2-6
21Be selected from hydrogen, halogen ,-(C
1-C
3) alkyl ,-(C
3-C
4) cycloalkyl ,-(C
3-C
4) cycloalkenyl group ,-O (C
1-C
2) alkyl and-S (C
1-C
2) alkyl.
8. each described formula (II) compound, wherein R among the claim 2-7
4Be hydrogen.
9. each described formula (II) compound, wherein R among the claim 2-8
1For-NH
2, and R
2For-O (CH
2)
mR
5, R wherein
5For-H ,-CO
2H or
, R wherein
6And R
7All be-OH.
10. each described formula (II) compound, wherein R among the claim 2-8
2For-O (CH
2)
mR
5, R wherein
5For-H ,-CO
2(C
1-C
4Alkyl), phenyl or quilt-CO
2H or-CO
2(C
1-C
4Alkyl) phenyl of Qu Daiing.
11. each described formula (II) compound, wherein R among the claim 2-8
2For-O (CH
2)
mR
5, wherein
R wherein
6And R
7For-O (C
1-C
4Alkyl) or work as R
6With R
7One of be-O (C
1-C
4Alkyl) time, another is-OH.
12. each described formula (II) compound, wherein R among the claim 2-11
3For-H ,-O (C
1-C
4Alkyl) or-(CH
2)
nR
8, wherein n=2 and R
8Be H or phenyl.
13. each described formula (II) compound, wherein R among the claim 2-11
3Be H, or-O (C
1-C
4Alkyl).
14. each described formula (II) compound, wherein R among the claim 2-11
3For-(CH
2)
nR
8, R wherein
8For-NR
9R
10,
Or-CN, wherein R
9And R
10For-(C
1-C
4) alkyl.
15. each described formula (II) compound, wherein R among the claim 2-14
4Be phenyl.
16. each described formula (II) compound, wherein R among the claim 2-14
4Be quilt-(C on the 2-of phenyl ring and 6-position
1-C
4) alkyl ,-(C
1-C
4) alkoxyl group, the phenyl that halogen or phenyl replace.
17. each described formula (II) compound, wherein R among the claim 2-14
4Be quilt-(C on the 3-of phenyl ring and 5-position
1-C
4) alkyl ,-(C
1-C
4) alkoxyl group, the phenyl that halogen or phenyl replace.
18. each described formula (II) compound, wherein R among the claim 2-14
4For-(C
6-C
14) alkyl or-(C
6-C
14) cycloalkyl.
19. each described formula (II) compound, wherein R among the claim 2-18
5Be H ,-CO
2H ,-CO
2(C
1-C
4Alkyl),
-NHSO
2(C
1-C
6) alkyl ,-CONHSO
2(C
1-C
6) alkyl, tetrazyl, phenyl, or quilt-CO
2H or-CO
2(C
1-C
4Alkyl) phenyl of Qu Daiing, wherein R
6And R
7Be independently of one another-OH or-O (C
1-C
4Alkyl), and m be 1-3.
20. each described formula (II) compound, wherein R among the claim 2-19
5Be H ,-CO
2H ,-CO
2(C
1-C
4Alkyl),
Phenyl, or quilt-CO
2H or-CO
2(C
1-C
4Alkyl) phenyl of Qu Daiing, wherein R
6And R
7Be independently of one another-OH or-O (C
1-C
4Alkyl), and m be 1-3.
21. each described formula (II) compound, wherein R among the claim 2-18
5Be H ,-CO
2H ,-CO
2(C
1-C
4Alkyl);
R wherein
6And R
7Be independently of one another-OH or-O (C
1-C
4Alkyl);-SO
3H ,-SO
3(C
1-C
4Alkyl), tetrazyl ,-CN ,-NH
2,-NHSO
2R
15-CONHSO
2R
15, R wherein
15For-(C
1-C
6) alkyl or-CF
3, phenyl or quilt-CO
2H or-CO
2(C
1-C
4Alkyl) phenyl of Qu Daiing, and m is 1-3.
22. each described formula (II) compound among the claim 2-21, wherein Z is a cyclohexenyl.
23. each described formula (II) compound among the claim 2-21, wherein Z is a phenyl.
24. each compound among the claim 2-23, described compound is selected from:
9-benzyl-5,7-dimethoxy-1,2,3,4-tetrahydro carbazole-4-carboxylic hydrazides;
9-benzyl-5,7-dimethoxy-1,2,3,4-tetrahydro carbazole-4-methane amide;
[9-benzyl-4-formamyl-7-methoxyl group 1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid sodium salt;
[9-benzyl-4-formamyl-7-methoxyl group carbazole-5-yl] ethoxyacetic acid;
Methyl [9-benzyl-4-formamyl-7-methoxyl group carbazole-5-yl] ethoxyacetic acid;
9-benzyl-7-methoxyl group-5-cyano group methoxyl group-1,2,3,4-tetrahydro carbazole-4-methane amide;
9-benzyl-7-methoxyl group-5-(1H-tetrazolium-5-base-methyl) oxygen base)-1,2,3,4-tetrahydro carbazole-4-methane amide;
The 9-[(phenyl) methyl]-5-formamyl-2-methyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-fluorophenyl) methyl]-5-formamyl-2-methyl-carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-aminomethyl phenyl) methyl]-5-formamyl-2-methyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(phenyl) methyl]-5-formamyl-2-(4-trifluoromethyl)-carbazole-4-yl } ethoxyacetic acid;
9-benzyl-5-(2-methanesulfonamido) oxyethyl group-7-methoxyl group 1,2,3,4-tetrahydro carbazole-4-methane amide;
9-benzyl-4-(2-methanesulfonamido) oxyethyl group-2-methoxyl group carbazole-5-methane amide;
9-benzyl-4-(2-fluoroform sulfonamido) oxyethyl group-2-methoxyl group carbazole-5-methane amide;
9-benzyl-5-methanesulfonamido methoxyl group-7-methoxyl group-1,2,3,4-tetrahydro carbazole-4-methane amide;
9-benzyl-4-methanesulfonamido methoxyl group-carbazole-5-methane amide;
[5-formamyl-2-amyl group-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-2-(1-methylethyl)-9-(phenmethyl) carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-9-(phenyl methyl)-2-[(three (1-methylethyl) silyl) the oxygen ylmethyl] carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-2-phenyl-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-2-(4-chloro-phenyl-)-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-2-(2-furyl)-9-(phenyl methyl) carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-9-(phenyl methyl)-2-[(three (1-methylethyl) silyl) the oxygen ylmethyl] carbazole-4-yl] the ethoxyacetic acid lithium salts;
The 9-[(2-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-benzyl phenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(1-naphthyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(3,5-3,5-dimethylphenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-iodophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2,3-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2,6-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2,6-dichlorophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
[9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid;
The 9-[(2-pyridyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-pyridyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
[9-benzyl-4-formamyl-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid;
[9-benzyl-5-formamyl-1-methyl carbazole-4-yl] ethoxyacetic acid;
[9-benzyl-4-formamyl-8-fluoro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid;
[9-benzyl-4-formamyl-8-chloro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid;
5-formamyl-9-(phenyl methyl)-2-[[(propylene-3-yl) oxygen base] methyl] carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-9-(phenmethyl) 2-[(propoxy-) methyl] carbazole-4-yl] ethoxyacetic acid;
9-benzyl-7-methoxyl group-5-((formamido group methyl) oxygen base)-1,2,3,4-tetrahydro carbazole-4-methane amide;
9-benzyl-7-methoxyl group-5-cyano group methoxyl group carbazole-4-methane amide;
9-benzyl-7-methoxyl group-5-((1H-tetrazolium-5-base-methyl) oxygen base) carbazole-4-methane amide;
9-benzyl-7-methoxyl group-5-((formamido group methyl) oxygen base) carbazole-4-methane amide; With
[9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid or their pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or salt.
25. each compound among the claim 2-23, described compound is selected from;
9-(phenyl) methyl]-5-formamyl-2-methyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-fluorophenyl) methyl]-5-formamyl-2-methyl-carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-aminomethyl phenyl) methyl]-5-formamyl-2-methyl-carbazole-4-yl } ethoxyacetic acid;
The 9-[(phenyl) methyl]-5-formamyl-2-(4-trifluoromethyl)-carbazole-4-yl } ethoxyacetic acid;
9-benzyl-5-(2-methanesulfonamido) oxyethyl group-7-methoxyl group-1,2,3,4-tetrahydro carbazole-4-methane amide;
9-benzyl-4-(2-methanesulfonamido) oxyethyl group-2-methoxyl group carbazole-5-methane amide;
9-benzyl-4-(2-fluoroform sulfonamido) oxyethyl group-2-methoxyl group carbazole-5-methane amide;
9-benzyl-5-methanesulfonamido methoxyl group-7-methoxyl group-1,2,3,4-tetrahydro carbazole-4-methane amide;
9-benzyl-4-methanesulfonamido methoxyl group-carbazole-5-methane amide;
[5-formamyl-2-amyl group-9-(phenmethyl) carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-2-(1-methylethyl)-9-(phenmethyl) carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-9-(phenmethyl)-2-[(three-(1-methylethyl) silyl) the oxygen ylmethyl] carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-2-phenyl-9-(phenmethyl) carbazole-4-yl] ethoxyacetic acid [5-formamyl-2-(4-chloro-phenyl-)-9-(phenmethyl) carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-2-(2-furyl)-9-(phenmethyl) carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-9-(phenmethyl)-2-[(three-(1-methylethyl) silyl) the oxygen ylmethyl] carbazole-4-yl] the ethoxyacetic acid lithium salts;
The 9-[(phenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
(9-[(3-Phenoxyphenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-benzyl phenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(1-naphthyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(3,5-3,5-dimethylphenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-iodophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2,3-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2,6-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
9-[(2,6-dichlorophenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-Trifluoromethoxyphen-l) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(2-xenyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
[9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid;
The 9-[(2-pyridyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
The 9-[(3-pyridyl) methyl]-5-formamyl carbazole-4-yl } ethoxyacetic acid;
[9-benzyl-4-formamyl-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid;
[9-benzyl-5-formamyl-1-methyl carbazole-4-yl] ethoxyacetic acid;
[9-benzyl-4-formamyl-8-fluoro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid;
[9-benzyl-5-formamyl-1-fluorine carbazole-4-yl] ethoxyacetic acid;
[9-benzyl-4-formamyl-8-chloro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid;
[9-benzyl-5-formamyl-1-chlorine carbazole-4-yl] ethoxyacetic acid;
[the 9-[(cyclohexyl) methyl]-5-formamyl carbazole-4-yl] ethoxyacetic acid;
[the 9-[(cyclopentyl) methyl]-5-formamyl carbazole-4-yl] ethoxyacetic acid;
5-formamyl-9-(phenmethyl)-2-[[(propylene-3-yl) oxygen base] methyl] carbazole-4-yl] ethoxyacetic acid;
[5-formamyl-9-(phenmethyl)-2-[(propoxy-) methyl] carbazole-4-yl] ethoxyacetic acid;
9-benzyl-7-methoxyl group-5-((formamido group methyl) oxygen base)-1,2,3,4-tetrahydro carbazole-4-methane amide;
9-benzyl-7-methoxyl group-5-cyano group methoxyl group-carbazole-4-methane amide;
9-benzyl-7-methoxyl group-5-((1H-tetrazolium-5-base-methyl) oxygen base)-carbazole-4-methane amide;
9-benzyl-7-methoxyl group-5-((formamido group methyl) oxygen base)-carbazole-4-methane amide; With
[9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid or their pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or salt.
26. each described compound among the claim 1-23, wherein prodrug derivant is a methyl, ethyl, propyl group, sec.-propyl, butyl, morpholino ethyl or diethyl glycolamide ester.
27. a pharmaceutical preparation wherein contains each described formula I compound and pharmaceutically acceptable carrier or thinner among the claim 1-23.
28. one kind is suitable for treatment and suppresses sPLA
2The pharmaceutical preparation of relevant illness wherein contains each described formula I compound and pharmaceutically acceptable carrier or thinner among the claim 1-23.
29. selectivity inhibition sPLA in the Mammals that needs are so treated
2Method, this method comprises formula (I) compound or its pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or the salt to described administration treatment significant quantity:
Wherein: Z is a cyclohexenyl, or phenyl, R
20Be selected from group (a), (b) and (c), wherein:
(a) be-(C5-C20) alkyl ,-(C5-C20) alkenyl ,-(C5-C20) alkynyl group, carbocylic radical, or heterocyclic radical, or
(b) be by group among one or more independent (a) that substituting group replaced of not interfering with each other that select; Or
(c) be group-(L)-R
80Wherein, (L)-for containing 1-12 divalent linker that is selected from carbon, hydrogen, oxygen, nitrogen and sulphur atom; Wherein-(L)-and the combination of middle atom is selected from (i) and has only carbon and hydrogen, (ii) has only a sulphur, (iii) has only an oxygen, (iv) has only one or two nitrogen and hydrogen, and (v) have only carbon, hydrogen and a sulphur and (vi) have only carbon, hydrogen and oxygen; And R wherein
80For being selected from (a) or group (b); R
21Be the substituting group that does not interfere with each other, wherein f is 1-3; R
1For-NHNH
2,-NH
2, or-CONH
2R
2 'Be selected from group-OH and-O (CH
2)
tR
5 ', wherein
R
5 'Be H ,-CN ,-NH
2,-CONH
2,-CONR
9R
10,-NHSO
2R
15-CONHSO
2R
15, R wherein
15For-(C
1-C
6) alkyl or-CF
3Phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that replaces of alkyl; With-(L
a)-(acidic-group), wherein-(L
a)-for the acid with the basic length of 1-7 acid connection connects base, and t is 1-5; R
3 'Be selected from the substituting group that does not interfere with each other, carbocylic radical, the carbocylic radical that substituting group replaced that is not interfered with each other, heterocyclic radical and the heterocyclic radical that substituting group replaced that is not interfered with each other.
30. selectivity inhibition sPLA in the Mammals that needs are so treated
2Method, this method comprises formula (II) compound or its pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or the salt to described administration treatment significant quantity:
Wherein: R
1For-NHNH
2Or-NH
2R
2Be selected from group-OH and-O (CH
2)
mR
5, wherein
R
5Be H ,-CO
2H ,-CONH
2,-CO
2(C
1-C
4Alkyl);
R wherein
6And R
7Be independently of one another-OH or-O (C
1-C
4) alkyl;-SO
3H ,-SO
3(C
1-C
4Alkyl), tetrazyl ,-CN ,-NH
2,-NHSO
2R
15-CONHSO
2R
15, R wherein
15For-(C
1-C
6) alkyl or-CF
3Phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that alkyl replaces, wherein m is 1-3; R
3Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-CONH
2,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be independently-(C
1-C
4) alkyl, or-phenyl (C
1-C
4) alkyl, and n is 1-8; And R
4Be H ,-(C
5-C
14) alkyl ,-(C
3-C
14) cycloalkyl, pyridyl, phenyl or be selected from the following phenyl that substituting group replaced :-(C by 1-5
1-C
6) alkyl, halogen ,-CF
3,-OCF
3,-(C
1-C
4) alkoxyl group ,-CN ,-(C
1-C
4) alkylthio, phenyl (C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, phenyl, phenoxy group or naphthyl; Z is a cyclohexenyl, or phenyl.
31. each described method in claim 30 or 31, Mammals is wherein behaved.
32. alleviate sPLA for one kind
2The method of the pathology effect of relative disease, this method comprise that its consumption should be enough to suppress sPLA to each compound among the administration claim 1-23 of this treatment of needs
2Thereby the lipid acid of mediation discharges and suppresses or prevent the formation of arachidonic acid cascade and harmful product thereof.
33. each described compound can be alleviated sPLA in preparation among the claim 1-23
2Application in the medicine of the pathological effect of relative disease, this application comprise the administration formula I compound that needs are so treated.
34. one kind is suppressed sPLA
2Method, this method comprises makes sPLA
2Contact with each described compound among the claim 1-23.
35. the method for the following disease of treatment: Sepsis, septic shock, rheumatoid arthritis, osteoarthritis, apoplexy, apoptosis, asthma, chronic bronchitis, acute bronchitis, cystic fibrosis of the pancreas, inflammatory bowel, or pancreatitis, this method comprises formula I compound or its pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or the salt of curee's administering therapeutic significant quantity that needs are so treated:
Wherein: Z is a cyclohexenyl, or phenyl, R
20Be selected from group (a), (b) and (c), wherein:
(a) be-(C5-C20) alkyl ,-(C5-C20) alkenyl ,-(C5-C20) alkynyl group, carbocylic radical, or heterocyclic radical, or
(b) be by group among one or more independent (a) that substituting group replaced of not interfering with each other that select; Or
(c) be group-(L)-R
80Wherein, (L)-for containing 1-12 divalent linker that is selected from carbon, hydrogen, oxygen, nitrogen and sulphur atom; Wherein-(L)-and the combination of middle atom is selected from (i) and has only carbon and hydrogen, (ii) has only a sulphur, (iii) has only an oxygen, (iv) has only one or two nitrogen and hydrogen, and (v) have only carbon, hydrogen and a sulphur and (vi) have only carbon, hydrogen and oxygen; And R wherein
80For being selected from (a) or group (b); R
21Be the substituting group that does not interfere with each other, wherein f is 1-3; R
1For-NHNH
2,-NH
2, or-CONH
2R
2 'Be selected from group-OH and-O (CH
2)
tR
5 ', wherein
R
5 'Be H ,-CN ,-NH
2,-CONH
2,-CONR
9R
10,-NHSO
2R
15-CONHSO
2R
15, R wherein
15For-(C
1-C
6) alkyl or-CF
3Phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that replaces of alkyl; With-(L
a)-(acidic-group), wherein-(L
a)-for the acid with the basic length of 1-7 acid connection connects base, and t is 1-5; R
3 'Be selected from the substituting group that does not interfere with each other, carbocylic radical, the carbocylic radical that substituting group replaced that is not interfered with each other, heterocyclic radical and the heterocyclic radical that substituting group replaced that is not interfered with each other.
36. the method for the following disease of treatment: Sepsis, septic shock, rheumatoid arthritis, osteoarthritis, apoplexy, apoptosis, asthma, chronic bronchitis, acute bronchitis, cystic fibrosis of the pancreas, inflammatory bowel, or pancreatitis, this method comprises formula (II) compound or its pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or the salt of curee's administering therapeutic significant quantity that needs are so treated:
Wherein: Z is a cyclohexenyl, or phenyl, R
21Be the substituting group that does not interfere with each other; R
1For-NHNH
2Or-NH
2R
2Be selected from group-OH and-O (CH
2)
mR
5, wherein
R
5Be H ,-CO
2H ,-CONH
2,-CO
2(C
1-C
4Alkyl);
R wherein
6And R
7Be independently of one another-OH or-O (C
1-C
4) alkyl;-SO
3H ,-SO
3(C
1-C
4Alkyl), tetrazyl ,-CN ,-NH
2,-NHSO
2R
15-CONHSO
2R
15, R wherein
15For-(C
1-C
6) alkyl or-CF
3Phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that alkyl replaces, wherein m is 1-3; R
3Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl; Or-(CH
2)
n 8, R wherein
8Be H ,-CONH
2,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be independently-(C
1-C
4) alkyl, or-phenyl (C
1-C
4) alkyl, and n is 1-8; And R
4Be H ,-(C
5-C
14) alkyl ,-(C
3-C
14) cycloalkyl, pyridyl, phenyl or be selected from the following phenyl that substituting group replaced :-(C by 1-5
1-C
6) alkyl, halogen ,-CF
3,-OCF
3,-(C
1-C
4) alkoxyl group ,-CN ,-(C
1-C
4) alkylthio, phenyl (C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, phenyl, phenoxy group or naphthyl; Z is a cyclohexenyl, or phenyl.
37. the method for the pathology effect of the following disease of each described alleviation among the claim 30-31: Sepsis, septic shock, adult respiratory distress syndrome, pancreatitis, suffer a shock due to the wound, bronchial asthma, allergic rhinitis, rheumatoid arthritis, cystic fibrosis of the pancreas, apoplexy, acute bronchitis, chronic bronchitis, acute bronchiolitis, chronic bronchiolitis, osteoarthritis, gout, arthritis vertebralis, ankylosing spondylitis, Josef Reiter disease syndrome, arthropathia psoriatica, the vertebra inflammatory bowel, teenager's property joint disease, or teenager's property ankylosing spondylitis, reactive arthropathy, infective arthritis or infection posterior joint inflammation, gonococcal arthiritis, tuberculous arthritis, viral arthritis, arthritis fungosa, syphilitic arthritis, Lyme disease is with " vascular inflammatory syndromes " relevant sacroiliitis, the nodositas polyarthritis, allergic angiitis, Luegenec granulomatosis, polymyalgia rheumatica, joint cell arteritis, calcium crystallization deposition joint disease, pseudogout, nonarticular rheumatism, bursitis, tenosynovitis goes up (condyle) scorching (tennis elbow), carpal tunnel syndrome, reusability damage (typewriting), various forms of sacroiliitis, neuropathy is because of property joint disease (neurogenic arthrosis), hemarthrosis, Heng Nuohe-She Enlaiyin (Henoch-Schonlein) purpura, hpertrophic osteoarthropathy, multicentric reticulohistiocytosis, the sacroiliitis relevant with some disease, surcoilosis, hemochromatosis, reaping hook cytopathy and other hemoglobinopathy, hyperlipoproteinemia disease, hypogammaglobulinemia disease, hyperparathyroidism, acromegaly, familial Mediterranean fever, the Behat disease, systemic lupus erythematous, or relapsing polychondritis and relative disease, this method comprise the formula I compound of the administration treatment significant quantity that needs are so treated.
38. following formula: compound:
Wherein PG is sour protecting group; R
21Be the substituting group that does not interfere with each other; R
12Be H or CH
2R
4, R wherein
4Be H ,-(C
5-C
14) alkyl ,-(C
3-C
14) cycloalkyl, pyridyl, phenyl or be selected from the following phenyl that substituting group replaced :-(C by 1-5
1-C
6) alkyl, halogen ,-CF
3,-OCF
3,-(C
1-C
4) alkoxyl group ,-CN ,-(C
1-C
4) alkylthio, phenyl (C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, phenyl, phenoxy group ,-OR
9R wherein
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl base-phenyl (C
1-C
4) alkyl; Tetrazolium; Quilt-(C
1-C
4) alkyl or-(C
1-C
4) tetrazolium that replaces of alkyl phenyl; Or naphthyl; R
3 (a)Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkenyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, or-phenyl (C
1-C
4) alkyl, and n is 1-8; Z is cyclohexenyl or phenyl; With X be halogen.
39. following formula: compound:
Wherein PG is sour protecting group; R
21Be the substituting group that does not interfere with each other; And R
3 (a)Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkenyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, or-phenyl (C
1-C
4) alkyl, and n is 1-8.
40. formula (IV) compound:
Wherein, PG is sour protecting group; R
21Be the substituting group that does not interfere with each other; R
12Be H or CH
2R
4, R wherein
4Be H ,-(C
5-C
14) alkyl ,-(C
3-C
14) cycloalkyl, pyridyl, phenyl or be selected from the following phenyl that substituting group replaced :-(C by 1-5
1-C
6) alkyl, halogen ,-CF
3,-OCF
3,-(C
1-C
4) alkoxyl group ,-CN ,-(C
1-C
4) alkylthio, phenyl (C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, phenyl, phenoxy group ,-OR
9R wherein
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl-(C
1-C
4) alkyl phenyl or-phenyl (C
1-C
4) alkyl; Tetrazolium; Quilt-(C
1-C
4) alkyl or-(C
1-C
4) tetrazolium that replaces of alkyl phenyl; Or naphthyl; R
3 (a)Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkyl ,-(C
1-C
6) alkoxyl group (C
1-C
6) alkenyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be hydrogen independently ,-CF
3, phenyl ,-(C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, or-phenyl (C
1-C
4) alkyl, and n is 1-8; R
11For-OH ,=O ,-O (C
1-C
4) alkyl or-O (CH
2) R
15, R wherein
15For-CO
2R
16,-SO
3R
16, P (O) (OR
16)
2, or-P (O) (OR
16) H, wherein R
16Be sour protecting group; With A and Z be phenyl or cyclohexenyl independently of one another, its condition is that A and Z can not be phenyl simultaneously.
41. preparation formula (II) compound or its pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, the method for prodrug derivant or salt:
Wherein: Z is a cyclohexenyl, or phenyl, R
21Be the substituting group that does not interfere with each other; R
1For-NHNH
2Or-NH
2R
2Be selected from group-OH and-O (CH
2)
mR
5, wherein
R
5Be H ,-CO
2H ,-CO
2(C
1-C
4Alkyl);
R wherein
6And R
7Be independently of one another-OH or-O (C
1-C
4) alkyl;-SO
3H-,-SO
3(C
1-C
4Alkyl), tetrazyl ,-CN ,-NH
2,-NHSO
2R
15-CONHSO
2R
15, R wherein
15For-(C
1-C
6) alkyl or-CF
3Phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that alkyl replaces, wherein m is 1-3; R
3Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-CONH
2,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be independently-(C
1-C
4) alkyl or-phenyl-(C
1-C
4) alkyl, and n is 1-8; And R
4Be H ,-(C
5-C
14) alkyl ,-(C
3-C
14) cycloalkyl, pyridyl, phenyl or be selected from the following phenyl that substituting group replaced :-(C by 1-5
1-C
6) alkyl, halogen ,-CF
3,-OCF
3,-(C
1-C
4) alkoxyl group ,-CN ,-(C
1-C
4) alkylthio, phenyl (C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, phenyl, phenoxy group or naphthyl; This method comprises:
A) esterification formula XVI compound:
Wherein X is a halogen; Form formula XV compound:
Wherein PG is sour protecting group,
B) reduction-type XV compound formation formula XIV compound:
Wherein PG is sour protecting group,
C) shrinking type XIV compound and formula XIII compound:
R wherein
3 (a)Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
6) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be independently-(C
1-C
4) alkyl or-phenyl (C
1-C
4) alkyl, and n is 1-8; Form formula XII compound:
D) cyclization formula XII compound forms formula XI compound:
E) use formula XCH
2R
4Alkylating agent, wherein X is a halogen, alkylation formula XI compound forms formula X compound:
F) dehydrogenation formula X compound forms formula IX compound:
G) amination formula IX compound forms formula VIII compound:
H) use formula XCH
2R
15Alkylating agent, wherein X is a halogen, and R
15For-CO
2R
16,-SO
3R
16,-P (O) (OR
16)
2, or-P (O) (OR
16) H, wherein R
16Be sour protecting group, alkylation formula VIII compound forms formula VII compound:
I) hydrolyzing type VII compound randomly forms formula I compound, and randomly makes formula I compound salify.
42. the method for preparation formula II compound or its pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or salt:
Wherein: Z is a cyclohexenyl, or phenyl, R
21Be the substituting group that does not interfere with each other; R
1For-NHNH
2Or-NH
2R
2Be selected from group-OH and-O (CH
2)
mR
5, wherein
R
5Be H ,-CO
2H ,-CONH
2,-CO
2(C
1-C
4Alkyl);
R wherein
6And R
7Be independently of one another-OH or-O (C
1-C
4) alkyl;-SO
3H ,-SO
3(C
1-C
4Alkyl), tetrazyl ,-CN ,-NH
2,-NHSO
2R
15-CONHSO
2R
15, R wherein
15For-(C
1-C
6) alkyl or-CF
3Phenyl or quilt-CO
2H or-CO
2(C
1-C
4) phenyl that alkyl replaces, wherein m is 1-3; R
3Be H ,-O (C
1-C
4) alkyl, halogen ,-(C
1-C
6) alkyl, phenyl ,-(C
1-C
4) alkyl phenyl; Quilt-(C
1-C
6) alkyl, halogen or-CF
3The phenyl that replaces;-CH
2OSi (C
1-C
6) alkyl, furyl, thienyl ,-(C
1-C
6) hydroxyalkyl; Or-(CH
2)
nR
8, R wherein
8Be H ,-CONH
2,-NR
9R
10,-CN or phenyl, wherein R
9And R
10Be independently-(C
1-C
4) alkyl or-phenyl-(C
1-C
4) alkyl, and n is 1-8; And R
4Be H ,-(C
5-C
14) alkyl ,-(C
3-C
14) cycloalkyl, pyridyl, phenyl or be selected from the following phenyl that substituting group replaced :-(C by 1-5
1-C
6) alkyl, halogen ,-CF
3,-OCF
3,-(C
1-C
4) alkoxyl group ,-CN ,-(C
1-C
4) alkylthio, phenyl (C
1-C
4) alkyl ,-(C
1-C
4) alkyl phenyl, phenyl, phenoxy group or naphthyl; The method comprising the steps of:
A) esterification formula XVI compound:
Wherein X is a halogen, forms formula XV compound:
Wherein PG is sour protecting group;
B) shrinking type XV compound and formula XVII compound:
Form formula XVIII compound:
C) cyclisation formula XVIII compound formation formula XIX compound:
D) use formula XCH
2R
4Alkylating agent, wherein X is a halogen, alkylation formula XIX compound forms formula XX compound:
E) dealkylation formula XX compound, production IX compound:
F) amination formula IX compound forms formula VIII compound:
G) use formula XCH
2R
15Alkylating agent, wherein X is a halogen, and R
15For-CO
2R
16,-SO
3R
16, P (O) (OR
16)
2, or-P (O) (OR
16) H, wherein R
16Be sour protecting group, alkylation formula VIII compound forms formula VII compound:
H) hydrolyzing type VII compound randomly forms formula I compound, and randomly makes formula I compound salify.
43. be selected from following compound:
(3-methoxycarbonyl-2-bromobenzene amido)-5-methyl-cyclohexyl-2-alkene-1-ketone;
5-methoxycarbonyl-1,2-dihydro-2-methyl-9H-carbazole-4-(3H)-ketone;
9-benzyl-5,7-dimethoxy-1,2,3,4-tetrahydro carbazole-4-methane amide;
9-benzyl-5-hydroxyl-7-methoxyl group-1,2,3,4-tetrahydro carbazole-4-methane amide;
[9-benzyl-4-formamyl-7-methoxyl group-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid ethyl ester;
9-benzyl-4-formamyl-5,7-dimethoxy carbazole;
9-benzyl-4-formamyl-5-hydroxyl-7-methoxyl group carbazole;
[9-benzyl-4-formamyl-7-methoxyl group carbazole-5-yl] ethoxyacetic acid methyl esters;
[(2,9-dibenzyl-4-formamyl-1,2,3,4-tetrahydrochysene-β-carbazole-5-yl) oxygen base] ethyl acetate;
(3-methoxycarbonyl-2-bromobenzene amido)-5-methyl-cyclohexyl-2-alkene-1-ketone; 5-methoxycarbonyl-1,2-dihydro-2-methyl-9H-carbazole-4 (3H)-ketone; [(phenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, 2-dihydro carbazole-4 (3H)-ketone; [(phenyl) methyl]-2-methyl-4-hydroxy-5-methyl ester group carbazole; [(phenyl) methyl]-2-methyl-4-hydroxyl-5-formamyl carbazole; [(phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(3-fluorophenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, 2-dihydro carbazole-4 (3H)-ketone; [(3-fluorophenyl) methyl]-2-methyl-4-hydroxy-5-methyl ester group carbazole; [(3-fluorophenyl) methyl]-2-methyl-4-hydroxyl-5-formamyl carbazole; [(3-fluorophenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(3-aminomethyl phenyl) methyl]-5-methoxycarbonyl-2-methyl isophthalic acid, 2-dihydro carbazole-4 (3H)-ketone; [(3-aminomethyl phenyl) methyl]-2-methyl-4-hydroxy-5-methyl ester group carbazole; [(3-aminomethyl phenyl) methyl]-2-methyl-4-hydroxyl-5-formamyl carbazole; [(3-aminomethyl phenyl) methyl]-2-methyl-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; (3-methoxycarbonyl-2-bromobenzene amido)-5-(4-trifluoromethyl) hexamethylene-2-alkene-1-ketone; 5-methoxycarbonyl-1,2-dihydro-2-(4-trifluoromethyl)-9H-carbazole-4 (3H)-ketone; [(phenyl) methyl]-5-methoxycarbonyl-2-(4-trifluoromethyl)-1,2-dihydro carbazole-4 (3H)-ketone; [(phenyl) methyl]-2-(4-trifluoromethyl)-4-hydroxy-5-methyl ester group carbazole; [(phenyl) methyl]-2-(4-trifluoromethyl)-4-hydroxyl-5-formamyl carbazole; [(phenyl) methyl]-2-(4-trifluoromethyl)-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; (2-bromo-3-methoxycarbonyl anilino)-5-amyl group hexamethylene-2-alkene-1-ketone; 5-methoxycarbonyl-1,2-dihydro-2-amyl group-9H-carbazole-4 (3H)-ketone; 5-methoxycarbonyl-1,2-dihydro-2-amyl group-9-(phenyl methyl) carbazole-4-(3H)-ketone; 5-methoxycarbonyl-4-hydroxyl-2-amyl group-9-(phenmethyl) carbazole; 5-formamyl-4-hydroxyl-2-amyl group-9-(phenmethyl) carbazole; [5-formamyl-2-amyl group-9-(phenmethyl) carbazole-4-yl] ethoxyacetic acid methyl esters; (2-bromo-3-methoxycarbonyl anilino)-5-[(1-methyl) ethyl] hexamethylene-2-alkene-1-ketone; 5-methoxycarbonyl-1,2-dihydro-2-(1-methylethyl)-9H-carbazole-4 (3H)-ketone; 5-methoxycarbonyl-1,2-dihydro-2-(1-methylethyl)-9-(phenyl methyl) carbazole-4 (3H)-ketone; 5-methoxycarbonyl-4-hydroxyl-2-(1-methylethyl)-9-(phenmethyl) carbazole; 5-formamyl-4-hydroxyl-2-(1-methylethyl)-9-(phenmethyl) carbazole;
[5-formamyl-2-(1-methylethyl)-9-(phenmethyl) carbazole-4-yl] ethoxyacetic acid methyl esters;
(2-bromo-3-methoxycarbonyl anilino)-5-(methylol) hexamethylene-2-alkene-1-ketone;
5-methoxycarbonyl-1,2-dihydro-2-(2-methylol)-9H-carbazole-4 (3H)-ketone;
5-methoxycarbonyl-1,2-dihydro-2-(methylol)-9-(phenyl methyl) carbazole-4 (3H)-ketone;
[5-formamyl-9-(phenmethyl)-2-[three (1-methylethyl) silyl) the oxygen methyl] carbazole-4-yl] the ethoxyacetic acid methyl esters;
(2-bromo-3-methoxycarbonyl anilino)-5-phenyl hexamethylene-2-alkene-1-ketone;
5-methoxycarbonyl-1,2-dihydro-2-phenyl-9H-carbazole-4 (3H)-ketone;
5-methoxycarbonyl-1,2-dihydro-2-phenyl-9-(phenyl methyl) carbazole-4 (3H)-ketone;
5-methoxycarbonyl-4-hydroxyl-2-phenyl-9-(phenmethyl) carbazole;
5-formamyl-4-hydroxyl-2-phenyl-9-(phenmethyl) carbazole;
[5-formamyl-2-phenyl-9-(phenmethyl) carbazole-4-yl] ethoxyacetic acid methyl esters;
(2-bromo-3-methoxycarbonyl anilino)-5-(4-chloro-phenyl-) hexamethylene-2-alkene-1-ketone;
5-methoxycarbonyl 1,2-dihydro-2-(4-chloro-phenyl-)-9H-carbazole-4 (3H)-ketone;
5-methoxycarbonyl 1,2-dihydro-2-(4-chloro-phenyl-)-9-(phenyl methyl) carbazole-4 (3H)-ketone;
5-methoxycarbonyl-2-(4-chloro-phenyl-)-4-hydroxyl-9-(phenmethyl) carbazole;
5-formamyl-2-(4-chloro-phenyl-)-4-hydroxyl-9-(phenmethyl) carbazole;
[5-formamyl-2-(4-chloro-phenyl-)-9-(phenmethyl) carbazole-4-yl] ethoxyacetic acid methyl esters;
(2-bromo-3-methoxycarbonyl anilino)-5-(2-furyl) hexamethylene-2-alkene-1-ketone;
5-methoxycarbonyl-1,2-dihydro-2-(2-furyl)-9H-carbazole-4 (3H)-ketone;
5-methoxycarbonyl-1,2-dihydro-2-(2-furyl)-9-(phenyl methyl) carbazole-4 (3H)-ketone;
5-methoxycarbonyl-2-(2-furyl)-4-hydroxyl-9-(phenmethyl) carbazole;
5-formamyl-2-(2-furyl)-4-hydroxyl-9-(phenmethyl) carbazole;
[5-formamyl-2-(2-furyl)-9-(phenmethyl) carbazole-4-yl] ethoxyacetic acid methyl esters; 5-methoxycarbonyl-1,2-dihydro-9-(phenmethyl)-2-[(three (1-methylethyl) silyl) the oxygen ylmethyl] carbazole-4 (3H)-ketone;
5-methoxycarbonyl-4-hydroxyl-9-(phenmethyl)-2-[(three (1-methylethyl) silyl) oxygen ylmethyl] carbazole;
5-formamyl-4-hydroxyl-9-(phenmethyl)-2-[(three (1-methylethyl) silyl) oxygen ylmethyl] carbazole;
[5-hydrogen base formyl radical-9-(phenmethyl)-2-[(three (1-methylethyl) silyl) the oxygen ylmethyl] carbazole-4-yl] the ethoxyacetic acid methyl esters; (3-methoxycarbonyl-2-chloroanilino) hexamethylene-2-alkene-1-ketone; 5-methoxycarbonyl-1,2-dihydro-9H-carbazole-4 (3H)-ketone; (3-methoxycarbonyl-2-bromobenzene amido) hexamethylene-2-alkene-1-ketone; [(phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(phenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(3-fluorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(3-fluorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(3-fluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(3-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester; [(3-chloro-phenyl-) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4-(3H)-ketone; [(3-chloro-phenyl-) methyl]-4-hydroxy-5-methyl ester group carbazole; [(3-chloro-phenyl-) methyl]-4-hydroxyl-5-formamyl carbazole; [(3-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester; [(3-Phenoxyphenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(3-Phenoxyphenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(3-Phenoxyphenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(3-Phenoxyphenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester; [(2-fluorophenyl) methyl]-5-methoxycarbonyl 1,2-dihydro carbazole-4 (3H)-ketone; [(2-fluorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(2-fluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(2-fluorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(2-trifluoromethyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(2-trifluoromethyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(2-trifluoromethyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(2-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(2-benzyl phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(2-benzyl phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(2-benzyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(2-benzyl phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(3-trifluoromethyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(3-trifluoromethyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(3-trifluoromethyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(3-trifluoromethyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(1-naphthyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4-(3H)-ketone; [(1-naphthyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(1-naphthyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(1-naphthyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(2-cyano-phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(2-cyano-phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(2-cyano-phenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(2-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(3-cyano-phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(3-cyano-phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(3-cyano-phenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(3-cyano-phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester; [(2-aminomethyl phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(2-aminomethyl phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(2-aminomethyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(2-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(3-aminomethyl phenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(3-aminomethyl phenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(3-aminomethyl phenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(3-aminomethyl phenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(3, the 5-3,5-dimethylphenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(3, the 5-3,5-dimethylphenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(3, the 5-3,5-dimethylphenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(3, the 5-3,5-dimethylphenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(3-iodophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(3-iodophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(3-iodophenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(3-iodophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(2-chloro-phenyl-) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(2-chloro-phenyl-) methyl]-4-hydroxy-5-methyl ester group carbazole; [(2-chloro-phenyl-) methyl]-4-hydroxyl-5-formamyl carbazole; [(2-chloro-phenyl-) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester; [(2, the 3-difluorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(2, the 3-difluorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(2, the 3-difluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(2, the 3-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(2, the 6-difluorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(2, the 6-difluorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(2, the 6-difluorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(2, the 6-difluorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(2, the 6-dichlorophenyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(2, the 6-dichlorophenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(2, the 6-dichlorophenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(2, the 6-dichlorophenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(3-Trifluoromethoxyphen-l) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(3-Trifluoromethoxyphen-l) methyl]-4-hydroxy-5-methyl ester group carbazole; [(3-Trifluoromethoxyphen-l) methyl]-4-hydroxyl-5-formamyl carbazole; [(3-Trifluoromethoxyphen-l) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; 2-methoxycarbonyl-6-nitro-2 '-methoxyl biphenyl; 9H-4-methoxyl group-5-methoxycarbonyl carbazole; [(2-xenyl) methyl]-4-methoxyl group-5-methoxycarbonyl carbazole; [(2-xenyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(2-xenyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(2-xenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid tert-butyl ester; [(2-xenyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; 9-benzyl-4-carboxyl-5-methoxyl group-1,2,3,4-tetrahydro carbazole, ethyl ester; 9-benzyl-4-formamyl-5-hydroxyl-1,2,3, the 4-tetrahydro carbazole; 9-benzyl-4-carboxyl-5-hydroxyl-1,2,3,4-tetrahydro carbazole, ethyl ester; [9-benzyl-4-formamyl-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid methyl esters; [(2-pyridyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4-(3H)-ketone; [(2-pyridyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(2-pyridyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(2-pyridyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; [(3-pyridyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone; [(3-pyridyl) methyl]-4-hydroxy-5-methyl ester group carbazole; [(3-pyridyl) methyl]-4-hydroxyl-5-formamyl carbazole; [(3-pyridyl) methyl]-5-formamyl carbazole-4-yl } the ethoxyacetic acid methyl esters; 5-methoxyl group-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic acid, ethyl ester; 9-benzyl-5-methoxyl group-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-carboxylic acid, ethyl ester; 9-benzyl-5-methoxyl group-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide; 9-benzyl-5-hydroxyl-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-4-methane amide; [9-benzyl-4-formamyl-8-methyl isophthalic acid, 2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid methyl esters; 5-formamyl-4-methoxyl group-1-methyl carbazole; 9-benzyl-5-formamyl-4-methoxyl group-1-methyl carbazole; 9-benzyl-5-formamyl-4-hydroxyl-1-methyl carbazole; [9-benzyl-5-formamyl-1-methyl carbazole-4-yl] ethoxyacetic acid methyl esters; 9-benzyl-5-methoxyl group-8-fluoro-1,2,3,4-tetrahydro carbazole-4-carboxylic acid, ethyl ester; 9-benzyl-5-methoxyl group-8-fluoro-1,2,3,4-tetrahydro carbazole-4-methane amide; 9-benzyl-5-hydroxyl-8-fluoro-1,2,3,4-tetrahydro carbazole-4-methane amide; [9-benzyl-4-formamyl-8-fluoro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid methyl esters; 9-benzyl-5-formamyl-4-methoxyl group-1-fluorine carbazole; 9-benzyl-5-formamyl-4-hydroxyl-1-fluorine carbazole; [9-benzyl-5-formamyl-1-fluorine carbazole-4-yl] ethoxyacetic acid methyl esters; 9-benzyl-5-methoxyl group-8-chloro-1,2,3,4-tetrahydro carbazole-4-carboxylic acid, ethyl ester; 9-benzyl-5-methoxyl group-8-chloro-1,2,3,4-tetrahydro carbazole-4-methane amide;
9-benzyl 5-hydroxyl-8-chloro-1,2,3,4-tetrahydro carbazole-4-methane amide;
[9-benzyl-4-formamyl-8-chloro-1,2,3,4-tetrahydro carbazole-5-yl] ethoxyacetic acid methyl esters;
9-benzyl-5-formamyl-4-methoxyl group-1-chlorine carbazole;
5-formamyl-4-hydroxyl-1-chlorine carbazole;
[5-formamyl-1-chlorine carbazole-4-yl] ethoxyacetic acid methyl esters;
[9-benzyl-5-formamyl-1-chlorine carbazole-4-yl] ethoxyacetic acid methyl esters;
[(cyclohexyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone;
[(cyclohexyl) methyl]-4-hydroxy-5-methyl ester group carbazole;
[(cyclohexyl) methyl]-4-hydroxyl-5-formamyl carbazole;
[(cyclohexyl) methyl]-5-formamyl-4-yl] the ethoxyacetic acid methyl esters;
[(cyclopentyl) methyl]-5-methoxycarbonyl-1,2-dihydro carbazole-4 (3H)-ketone;
[(cyclopentyl) methyl]-4-hydroxyl-5-formamyl carbazole;
[(cyclopentyl) methyl]-5-formamyl carbazole-4-yl] the ethoxyacetic acid methyl esters; Or its pharmaceutically useful racemic modification, solvate, tautomer, optically active isomer, prodrug derivant or salt.
44. the application of each compound in the medicine of the following disease of preparation treatment among the claim 1-23: Sepsis, septic shock, adult respiratory distress syndrome, pancreatitis, suffer a shock due to the wound, bronchial asthma, rhinallergosis, rheumatoid arthritis, cystic fibrosis of the pancreas, apoplexy, acute bronchitis, chronic bronchitis, acute bronchiolitis, chronic bronchiolitis, osteoarthritis, gout, arthritis vertebralis, ankylosing spondylitis, urethrooculosynovial syn, arthropathia psoriatica, the vertebra inflammatory bowel, teenager's property joint disease, or teenager's property ankylosing spondylitis, reactive arthropathy, infective arthritis or infection posterior joint inflammation, gonococcal arthiritis, tuberculous arthritis, viral arthritis, arthritis fungosa, syphilitic arthritis, Lyme disease is with " vascular inflammatory syndromes " relevant sacroiliitis, the nodositas polyarthritis, allergic angiitis, Luegenec granulomatosis, polymyalgia rheumatica, joint cell arteritis, calcium crystallization deposition joint disease, pseudogout, nonarticular rheumatism, bursitis, tenosynovitis goes up (condyle) scorching (tennis elbow), carpal tunnel syndrome, reusability damage (typewriting), various forms of sacroiliitis, neuropathy is because of property joint disease (neurogenic arthrosis), hemarthrosis, Heng Nuohe-She Enlaiyin Henoch-Schonlein purpura, hpertrophic osteoarthropathy, multicentric reticulohistiocytosis, the sacroiliitis relevant with some disease, surcoilosis, hemochromatosis, reaping hook cytopathy and other hemoglobinopathy, hyperlipoproteinemia disease, hypogammaglobulinemia disease, hyperparathyroidism, acromegaly, familial Mediterranean fever, the Behat disease, systemic lupus erythematous, or relapsing polychondritis and relative disease, this purposes comprise the formula I or the formula II compound of the administration treatment significant quantity that needs are so treated.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN99107687A CN1240210A (en) | 1998-04-17 | 1999-04-16 | Substituted tricyclic compound |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US09/062,328 | 1998-04-17 | ||
| CN99107687A CN1240210A (en) | 1998-04-17 | 1999-04-16 | Substituted tricyclic compound |
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| Publication Number | Publication Date |
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| CN1240210A true CN1240210A (en) | 2000-01-05 |
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| CN99107687A Pending CN1240210A (en) | 1998-04-17 | 1999-04-16 | Substituted tricyclic compound |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100446767C (en) * | 2001-01-31 | 2008-12-31 | H.隆德贝克有限公司 | Use of GAL3 receptor antagonists for treatment of. depression and/or anxiety and compounds useful in such methods |
| CN114920699A (en) * | 2022-05-31 | 2022-08-19 | 甘肃皓天化学科技有限公司 | Method for preparing 6-chloro-2-methyl-2H-indazole-5-amine |
-
1999
- 1999-04-16 CN CN99107687A patent/CN1240210A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100446767C (en) * | 2001-01-31 | 2008-12-31 | H.隆德贝克有限公司 | Use of GAL3 receptor antagonists for treatment of. depression and/or anxiety and compounds useful in such methods |
| CN114920699A (en) * | 2022-05-31 | 2022-08-19 | 甘肃皓天化学科技有限公司 | Method for preparing 6-chloro-2-methyl-2H-indazole-5-amine |
| CN114920699B (en) * | 2022-05-31 | 2024-03-19 | 甘肃皓天科技股份有限公司 | Method for preparing 6-chloro-2-methyl-2H-indazol-5-amine |
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