AP869A - 2,3-Substituted indole compounds as anti-inflammatory and analgesic agents. - Google Patents

2,3-Substituted indole compounds as anti-inflammatory and analgesic agents. Download PDF

Info

Publication number
AP869A
AP869A APAP/P/1998/001423A AP9801423A AP869A AP 869 A AP869 A AP 869A AP 9801423 A AP9801423 A AP 9801423A AP 869 A AP869 A AP 869A
Authority
AP
ARIPO
Prior art keywords
indol
chloro
acetic acid
carbonyl
alkyl
Prior art date
Application number
APAP/P/1998/001423A
Other versions
AP9801423A0 (en
Inventor
Kazunari Nakao
Rodney William Stevens
Kiyoshi Kawamura
Chikara Uchida
Hiroki Koike
Stephane Caron
Original Assignee
Pfizer
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Pfizer filed Critical Pfizer
Publication of AP9801423A0 publication Critical patent/AP9801423A0/en
Application granted granted Critical
Publication of AP869A publication Critical patent/AP869A/en

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
    • C07D209/04—Indoles; Hydrogenated indoles
    • C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
    • C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/10—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
    • C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/06—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/10—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pain & Pain Management (AREA)
  • Rheumatology (AREA)
  • Neurosurgery (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Indole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Abstract

This invention provides a compound of the following formula: Z or the pharmaceutically acceptable salts thereof wherein Z is OH, C\^ alkoxy, -NR"RJ or heterocycle; Q is selected from the following: (a) an optionally substituted phenyl, (b) an optionally substituted 6-membered monocyciic aromatic group containing one, two, three or four nitrogen atoMs). (c) an optionally substituted 5-membered monocyciic aromatic group containing one heteroatom selected from O, S and N and optionally containing one. two or three nitrogen atom(s) in addition to said heteroatom, (d) an optionally substituted C3.7 cycloalkyl and (e) an optionally substituted benzo-fuzed heterocycle; R1 is hydrogen. CM alkyl or halo; R: and RJ are independently hydrogen, OH, CM alkoxy. CM alkyl or CM aikyl substituted with halo, OH, CM alkoxy or CN; X is independently selected from H, halo, CM aikyl, halo-substituted C,. 4 alkyl, OH, CM alkoxy, halo-substiruted CM alkoxy, CM alkylthio, NO;, NH2, di-(Ci. 4 alkyl)amino and CN; and. n is 0, 1, 2. 3 and 4. This invention also provides a pharmaceutical composition useful for the treatment of a medical condition in which prostaglandins are implicated as padiogens.

Description

2,3-SUBSTITUTED INDOLE COMPOUNDS AS ANTI-INFLAMMATORY AND ANALGESIC AGENTS
Technical Field
This invention relates to novel 2,3-substituted indoles as pharmaceutical agents.
This invention specifically relates to compounds, compositions and methods for the treatment or alleviation of pain and inflammation and other inflammation-associated disorders, such as arthritis.
Background Art
Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used in treating pain and the signs and symptoms of arthritis because of their analgesic and antiinflammatory activity. It is accepted that common NSAIDs work by blocking, the activity of cyclooxygenase (COX), also known as prostaglandin G/H synthase (PGHS), the enzyme that converts arachidonic acid into prostanoids. Prostaglandins, especially prostaglandin Eg (PGEg), which is the predominant eicosanoid detected in inflammation conditions, are mediators of pain, fever and other symptoms associated ’
I with inflammation. Inhibition of the biosynthesis of prostaglandins has been a ( therapeutic target of anti-inflammatory drug discovery. The therapeutic use of < conventional NSAIDs is, however, limited due to drug associated side effects, j including life threatening ulceration and renal toxicity. An alternative to NSAIDs is f the use of corticosteriods, however, long term therapy can also result in severe side effects.
Recently, two forms of COX were identified, a constitutive isoform (COX-1) and an inducible isoform (COX-2) of which expression is upregulated at sites of inflammation (Vane, J. R.; Mitchell, J. A.; Appleton, I.; Tomlinson, A.; Bishop-Bailey, D.; Croxtoll, J.;Willoughby, D. A. Proc. Natl. Acad. Sci. USA, 1994, 91, 2046). COX-1 is thought to play a physiological role and to be responsible for gastrointestinal and renal protection. On the other hand, COX-2 appears to play a pathological role and to be the predominant isoform present in inflammation conditions. A pathological role for prostaglandins has been implicated in a number of human disease states including rheumatoid and osteoarthritis, pyrexia, asthma, bone resorption, cardiovascular diseases, nephrotoxicity, atherosclerosis, hypotension, shock, pain, cancer, and Alzheimer disease. The NSAIDs currently on market inhibit both isoforms of COX with little variation for selectivity, explaining their beneficial (inhibition of COX-2) and deleterious effects (inhibition of COX-1). It is believed that compounds that would selectively inhibit the biosynthesis of prostaglandins by intervention of the induction phase of the inducible enzyme cvclooxygenase-2 and/or by intervention of the activity of the enzyme cyclooxygenase-2 on arachidonic acid would provide alternate therapy to the use of NSAIDs or corticosteriods in that such compounds would exert anti-inflammatory effects without the adverse side effects associated with COX-1 inhibition. A variety of indole compounds are known and are disclosed in several patent applications. The International Publication Numbers WO 95/32379 discloses N-substituted indole compounds as cGMP-PDE Inhibitors. The International Publication Numbers WO 96/37467, WO 96/37469, UK Patent Publication GB 2283745 A and US Publication Number 5510368 disclose 2-methyl-N-substituted indole compounds as cyclooxygenase-2 Inhibitors. Also, a variety of indole compounds are disclosed as agents for controlling underwater fouling organisms in European Patent Publication Number 0 556 949 A2 by Konya, Kazumi et.al. Specifically, the International Publication Numbers WO 97/09308 discloses indole compounds as neuropeptide receptor antagonists. Besides, in Sci. Pharm. 64, 577 (1996), a process for preparing a 2-ester-substituted indoline is disclosed.
Brief Disclosure of the Invention
The present invention provides a compound of the following formula:
σ) or the pharmaceutically acceptable salts thereof wherein Z is OH, Ci_6 alkoxy, -NR2RJ or a group of the formula (II) or (III):
or
(II) (III) wherein r is 1, 2, 3 or 4, Y is a direct bond, O, S or NR4, and W is OH or -NR2R3; Q is selected from the following: (a) phenyl optionally substituted with one, two or three substituents independently selected from (a-1) halo, Cu alkyl, halo-substituted Cu alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO?, NH?, di-(CM alkyl)amino, Cm alkylamino, CN, HO-(Cm) alkyl, Cm alkoxy-Ci-4 alkyl, Cm alkylsulfonyl, aminosulfonyl, -NH?S(O)?NR2R3, acetyl, * -COOH, -C(0)0-Cm alkyl, Cm alkylsulfonylamino and C3.7 cycloalkyi, (a-2) aryl or -0-(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(Cm alkyl)amino, Cm alkylamino and CN, (a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Ci-4 alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(CM alkyl)amino, Cm alkylamino and CN, (a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Ci_ 4 alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO?, NH2, di-(CM alkyl)amino, Cm alkylamino and CN, (b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently
selected from the above group (a-1), (a-2), (a-3) and (a-4), (c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4); (d) C3.7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, Cm allyl, halo and halo-substituted Cj. 4 alkyl; and (e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1); R1 is hydrogen, Cm alkyl or halo; R2 and R3 are independently H, OH, Cm alkoxy, Cm alkyl or Cm alkyl substituted with halo, OH, Cm alkoxy, NH? or CN; R4 is hydrogen or Cm alkyl; X is independently selected from halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, NO?, ΝΉ?, di-(CM alkyl)amino, Cm alkylamino, CN, HO-(Cm) alkyl, Cm alkoxy-CM alkyl, Cm alkylsuifonyl, aminosulfonyl, -NH2S(O)2NR2NR3, acetyl, -COOH, -C(O)O-CM alkyl, Cm alkylsulfonylamino and C3.7 cycloalkyl; and n is 0, 1, 2, 3 or 4.
The indole compounds of the present invention exhibit inhibition of COX activity. Preferably compounds of this invention exhibit inhibitory activity against COX-2, with more preferable compounds having COX-2 selectivity.
Accordingly, the present invention also provides a pharmaceutical composition, useful for the treatment of a medical condition in which prostaglandins are implicated as pathogens, which comprises a compound of the formula (I) and the pharmaceutically acceptable salts thereof.
Further, the present invention provides a method for the treatment of a medical condition in which prostaglandins are implicated as pathogens, in a mammalian subject. which comprises administering to said subject a therapeutically effective amount of said pharmaceutical composition.
The medical conditions in which prostaglandins are implicated as pathogens, include the relief of pain, fever and inflammation of a variety of conditions including rheumatic fever, symptoms associated with influenza or other viral infections, common cold, low back and neck pain, dysmenorrhea, headache, toothache, sprains and strains, myositis, neuralgia, synovitis, arthritis including rheumatoid arthritis, degenerative joint disease (osteoarthritis), gout, ankylosing spondylitis, systemic lumpus erythematosus and juvenile arthritis, bursitis, bums, injuries following surgical and dental procedures.
The compounds and pharmaceutical composition of this invention may inhibit cellular neoplastic transformations and metastatic tumor growth and thus may be used in the treatment and/or prevention of cancers in the colon, breast, skin, esophagus, stomach, urinary bladder, lung and liver. The compounds and pharmaceutical composition of this invention were used in the treatment and/or prevention of cyclooxygenase-mediated proliferation disorders such as which occur in diabetic retinopathy and tumor angiogenesis.
The compounds and pharmaceutical composition of this invention may inhibit prostaniod-induced smooth muscle contraction by preventing the synthesis of contractile prostanoids, and thus may be of use in the treatment of dysmenorrhea, premature labor, asthma and eosinophil related disorders and in the treatment of neurodegenerative diseases such as Alzheimer's and Parkinson’s disease, and for the treatment of bone loss (treatment of osteoarthritis), stroke, seizures, migraine, multiple sclevosis, AIDS and encephaloathy.
By virtue of the COX-2 activity and/or specificity for COX-2 over COX-1, such compounds will prove useful as an alternative to conventional NSAIDs particularly where such NSAIDs may be contra-indicated such as in patients with ulcers (such as peptic ulcers and gastric ulcers), gastritis, regional enterotis, ulcerative colitis, diverticulitis or with a recurrent history of GI lesions, GI bleeding, coagulation disorders including anemia such as hypoprothrombinemia, haemophilia and other bleeding problems; kidney disease; prior to surgery of taking of anticoagulants.
Also, the present invention provides a compound of formula 7-VI:
wherein B is a suitable protecting group; Q is selected from the following: (a) phenyl optionally substituted with one, two or three substituents independently selected from (a-1) halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, NO?, NH2, di-(CM alkyl)amino, Cm alkylamino, CN, HO-(Cm) alkyl, Cm alkoxy-Ci. 4 alkyl, Cm alkylsulfonyl, aminosulfonyl, -NH2S(O)2NR2R3, acetyl, -COOH, -C(O)O-Cm alkyl, Cm alkylsulfonylamino and C3.7 cycloalkyl, (a-2) aryl or -O-(CH?)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(Cm alkyl)amino, Cm alkylamino and CN, (a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Cr-4 alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO2, NH?, di-(CM alkyl)amino, Cm alkylamino and CN,
(a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Cj. 4 alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(CM
alkyl)amino, Cm alkylamino and CN, (b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4), (c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4); (d) C3.7 cycloalkyl optionally substituted with one or two substituents * independently selected from OH, Cm alkyl, halo and halo-substituted Cj. 4 alkyl; and (e) a benzo-fuzed heterocycle optionally substituted with one, two or three 1 substituents independently selected from the group (a-1); R2 and R3 are independently H, OH, Cm alkoxy, Cm alkyl or Cm alkyl substituted 1 with halo, OH, Cm alkoxy, NH? or CN; j X is independently selected from halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm J alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, NO?, NH?, di-(CM alkyl)amino,
Cm alkylamino, CN, HO-(Cm) alkyl, Cm alkoxy-CM alkyl, Cm alkylsuifonyl, aminosulfonyl, -NH?S(O)?NR2NR3, acetyl, -COOH, -C(O)O-CM alkyl, CM alkylsulfonylamino and C3.7 cycloalkyl; R3 is Cm alkyl; and n is 0, 1, 2, 3 or 4.
Also, the present invention provides a compound of formula 7-V:
wherein B is a suitable protecting group; Q is selected from the following: (a) phenyl optionally substituted with one, two or three substituents independently selected from (a-1) halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(CM alkyl)amino, Cm alkylamino, CN, HO-(Cm) alkyl, Cm alkoxy-Cj. 4 alkyl, Cm alkylsulfonyl, aminosulfonyl, -NH?S(O)2NR2R'\ acetyl, -COOH, -C(O)O-Cm alkyl, Cm alkylsulfonylamino and C3.7 cycloalkyi, (a-2) aryl or -O-(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, Cm alkyl, halo-substituted CH alkyl, OH, Cm alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(Cm alkyl)amino, Cm alkylamino and CN, (a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Ci-4 alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(CM alkyl)amino, Cm alkylamino and CN, (a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Ci. 4 alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO?, NH?, di-(CM alkyl)amino, Cm alkylamino and CN, (b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4), (c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4); (d) C3-7 cycloalkyl optionally substituted with one or two substituents independently selected from OH, Cm alkyl, halo and halo-substituted Ci. 4 alkyl; and (e) a benzo-fuzed heterocycle optionally substituted with one, two or three substituents independently selected from the group (a-1); R2 and R3 are independently H, OH, Cm alkoxy, Cm alkyl or Cm alkyl substituted with halo, OH, Cm alkoxy, NH? or CN; X is independently selected from halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, NO?, NH?, di-(CM alkyl)amino, Cm alkylamino, CN, HO-(Cm) alkyl, Cm alkoxy-CM alkyl, Cm alkylsulfonyl, aminosulfonyl, -NH2S(O)2NR2NRJ, acetyl, -COOH, -C(0)0-Cm alkyl, Cm alkylsulfonylamino and C3-7 cycloalkyl; R3 is Cm alkyl; and n is 0, 1,2, 3 or 4.
Detailed Disclosure of the Invention
As used herein, "halo" is fluoro, chloro, bromo or iodo.
As used herein, the term "Cm alkyl" means straight or branched chain saturated radicals of 1 to 4 carbon atoms, including, but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, ferf-butyl, and the like.
As used herein, an example of “propyl” is n-propyl and isopropyl.
As used herein, an example of “butyl” is n-butyl, isobutyl, sec-butyl and tertbutyl.
As used herein, an example of “alkoxy” is methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, isobutoxy, sec-butoxy, teri-butoxy, and the like.
As used herein, an example of "alkylthio" is methvlthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, scc-butylthio, rerf-butylthio, and the like.
As used herein, an example of "di-(CM alkyl)amino” is dimethvlamino, diethylamino, dipropylamino, N-methyl-N-ethylamino, N-methyl-N-propylamino, N-methyl-N-butylamino, N-ethyl-N-propylamino, and the like.
As used herein, an example of “Cm alkylamino” is methylamino, ethylamino, n-propylammo, isopropylamino, n-butylamino, isobutylamino, sec-butylamino, tert-butylamino, and the like.
As used herein, an example of “HO-(CM)alkyl” is hydroxymethyl, hydroxyethyl (e.g., 1- hydroxyethyl and 2-hydroxyethyl), hydroxypropyl (e.g., 1- hydroxypropyl, 2-hydroxypropyl and 3-hydroxypropyl)
As used herein, an example of “Cm alkoxy-CM alkyl” is methoxymethyl, methoxyethyl, methoxypropyl, methoxybutyl, ethoxymethyl, ethoxyethyl, ethoxypropyl, and the like.
As used herein, the term "halo-substituted alkyl" refers to an alkyl radical as described above substituted with one or more halogens included, but not limited to, chloromethyl, dichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, 2,2,2-trichloroethyl, and the like.
As used herein, an example of “halo-substituted alkoxy“ is chloromethoxy, dichloromethoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trichloroethoxy, and the like.
As used herein, the term "C3.7 cycloalkyl" means carbocyclic radicals, of 3 to 7 carbon atoms, including, but not limited to cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, and the like.
As used herein, an example of “aryl“ is phenyl and naphthyl.
As used herein, a 5-membered monocyclic aromatic group usually has one heteroatom selected from O, S and N in the ring. In addition to said heteroatom, the monocyclic aromatic group may optionally have up to three N atoms in the ring. For example, the 5-membered monocyclic aromatic group includes thienyl, furyl, thiazolyl (e.g., 1,3-thiazolyl, 1,2-thiazolyl), imidazolyl, pyrrolyl, oxazolyl (e.g., 1,3-oxazolyl, 1,2-oxazolyl, isoxazolyl), pyrazolyl, tetrazolyl, triazolyl (e.g., 1,2,3-triazolyl, 1,2,4-triazolyl), oxadiazolyl (e.g., 1,2,3-oxadiazolyl), thiadiazolyl (e.g., 1,3,4-thiadiazolyl, 1,2,3-thiadiazolyl) and the like.
As used herein, an example of a 6-membered monocyclic aromatic group includes pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, triazinyl (e.g., 1,3,5-triazinyl), tetrazinyl and the like.
As used herein, an example of a benzo-fuzed heterocycle includes quinolyl, isoquinolyl, cinnolinyl, quinoxalinyl, benzoimidazolvl, benzothiazolyl, benzoxazolyl, benzofuranyl, benzothiophenyl, indolyl, isoindolyl, ΙΗ-indazolyl, quinazolinyl, phthalazinyl and the like.
As used herein, an example of (ethyl)(ethoxy)pyridyl includes 3-ethoxy-4-ethyl-2-pyridyl, 4-ethoxy-3-ethyl-2-pyridyl and the like.
As used herein, an example of (chloro)(ethyl)pyridyl includes 3-cloro-4-ethyl-2-pyridyl, 4-cloro-3-ethyl-2-pyridyl and the like.
As used herein, an example of (fluoro)(ethyl)phenyl includes 3-fluoro-4-ethyl-2-pyridyl, 4-fluoro-3-ethyl-2-pyridyl and the like.
Preferred compounds of this invention are those of the formula (I) wherein » Z is OH, Ci-6 alkoxy, dimethylamino, methylamino, amino, N-methoxy-N-methylamino, 2-cyanoethylamino, 2-hydroxyethylamino, pyrrolidinyl, piperidino, piperazinyl, N-methyl-piperazinyl, morpholino, methoxyamino, piperazynyl, aminopyrrolidinyl or aminoethylamino.
Further preferred compounds of this invention are those of the formula (I) wherein Z is OH or Ci-6 alkoxy; and Q is selected from the following: (a) phenyl optionally substituted with one, two or three substituents independently selected from (a-1) halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO?, NH?, di-(CM alkyl)amino, Cm alkylamino, CN, HO-(Cm) alkyl, Cm alkoxy-Ci. 4 alkyl, Cm alkylsulfonyl, aminosulfonyl, -NH2S(O)?NR~RJ, acetyl, -COOH, -C(O)O-Cm alkyl. Cm alkylsulfonylamino and C3.7 cycloalkyi, (a-2) aryl or -O-(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted with one, two or three substituents independently selected from halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, N02, NH?, di-(Cm alkyl)amino, Cm alkylamino and CN, (a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Ci_ 4 alkyl, halo-substituted Cm- alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO?, NH2, di-(CM alkyl)amino, Cm alkylamino and CN, (a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Ci_ 4 alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(CM alkyl)amino, Cm alkylamino and CN, * (b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4), (c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4); (d) C3.7 cycloalkyl selected from cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, and the said cycloalkyl being optionally substituted with one substituent selected from OH, methyl, ethyl, propyl, F, Cl and CF3; and (e) a benzo-fuzed heterocycle selected from quinolyl, isoquinolyl, cinnolinyl, quinoxalinyl, benzoimidazolyl, benzothiazolyl, benzoxazolyl, benzo furanyl, benzothiophenyl and indolyl, and the benzo-fuzed heterocycle being optionally substituted with one, two, or three substituents independently selected from the group (a-1).
Further preferred compounds of this invention are those of the formula (I) wherein Q is selected from the following: (a) phenyl optionally substituted with one, two or three substituents independently selected from (a-1) halo, Cm alkyl, halo-substituted Cw alkyl, OH, Cw alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(CM alkyl)amino, Cm alkylamino, CN, HO-(Cm) alkyl, Cm alkoxy-Ci-4 alkyl, Cm alkylsulfonyl, aminosulfonyl, -NH2S(O)2NR2RJ, acetyl, -COOH, -0(0)0-0m alkyl, Cm alkylsulfonylamino and C3-7 cycloalkyl, (a-2) aryl or -O-(CH2)n-aryl, and the aryl or aryl moiety being optionally substituted “with one, two or three substituents independently selected from halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, NO?, NH?, di-(Cm alkyl)amino, Cm alkylamino and CN, (a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Cm 4 alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO?, NH2, di-(CM alkyl)amino, Cm alkylamino and CN, (a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Ci-4 alkyl, halo-substituted Cm alkyd, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO?, NH?, di-(CM alkyl)amino, Cm alkylamino and CN, (b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4), (c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4); (d) cyclopropyl, cyclobutyl and cyclohexyl; and (e) quinolyl or isoquinolyl, and said quinolyl or isoquinolyl being optionally substituted with one substituent selected from the group halo, Cm alkyl, NH?, OH, Cm alkoxy and Cm halo-substituted alkyl.
Further preferred compounds of this invention are those of the formula (I) wherein Z is OH, Ci-6 alkoxy; Q is selected from the following: * (a) phenyl optionally substituted with one, two or three substituents independently selected from (a-1) halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(CiM alkyl)amino, Cm alkylamino, CN, HO-(Cm) alkyl, Cm alkoxy-Ci. 4 alkyl, Cm alkylsulfonyl, aminosulfonyl, -NH?S(O)2NR2RJ, acetyl, -COOH, -C(O)O-Ci_4 alkyl, CM alkylsulfonylamino and C3.7 cycloalkyi, (a-2) aryl or -O-(CH2)n-aryl, and the aryl or aryj moiety being optionally substituted with one, two or three substituents independently selected from halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(Cm alkyl)amino. Cm alkylamino and CN, (a-3) 5-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Ci-4 alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO2, NH2, di-(CM alkyl)amino, Cm alkylamino and CN, (a-4) 6-membered monocyclic aromatic group optionally substitued with one, two or three substituents independently selected from halo, Ci. 4 alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halosubstituted Cm alkoxy, Cm alkylthio, NO?, NH?, di-(CM alkyl)amino, Cm alkylamino and CN, (b) a 6-membered monocyclic aromatic group containing one, two, three or four nitrogen atom(s), and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4), (c) a 5-membered monocyclic aromatic group containing one heteroatom selected from O, S and N and optionally containing one, two or three nitrogen atom(s) in addition to said heteroatom, and said monocyclic aromatic group being optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4); and (e) isoquinolyl; * R1 is hydrogen or Cm alkyl; , R2 and R3 are independently H or methyl; ' X is independently selected from halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm | alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, NO?, NH?, di-(CM alkyl)amino, 1 Cm alkylamino, CN, HO-(Cm) alkyl, Cm alkoxy-CM alkyl, Cm alkylsuifonyl, aminosulfonyl, -NH?S(O)2NR2NR3, acetyl, -COOR4, Cm alkylsulfonylamino and C3.7 cycloalkyl; and n is 0, 1, 2, or 3.
Further preferred compounds of this invention are those of the formula (I) wherein Z is OH, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxyor or tert-butoxy; Q is selected from the following: (a) phenyl optionally substituted with one or two substituents independently selected from (a-1) halo, CM alkyl, halo-substituted CM alkyl, OH, Cm alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, HO-(Cm) alkyl, Cm alkoxy-CM alkyl, -COOH, Cm alkylsulfonylamino, nitro, Cm alkylsuifonyl and cyano, (a-2) phenyl or benzyloxy, and the phenyl or phenyl moiety of benzyloxy being optionally substituted with one substituent selected from Cm alkyl, halo-substituted Cm alkyd, halo, OH, Cm alkoxy, halosubstituted Cm alkoxy and NH?, (a-3) 5-membered monocyclic aromatic group selected from imidazolyl, thiazolyl, furyl, thienyl, pyrrolyl, tetrazolyl, triazolyl, oxazolyl, isoxazolyl, thiadiazolyl and pyrazolyl, and the 5-membered monocyclic aromatic group optionally being substitued with one substituent selected from Cm alkyl, halo-substituted Cm alkyl, halo, OH, Cm alkoxy, halo-substituted Cm alkoxy andNH2, (a-4) 6-membered monocyclic aromatic group selected from pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl, and the 6-membered monocyclic aromatic group optionally being substitued with one substituent selected from Cm alkyl, halo-substituted Cm alkyl, halo, OH, Cm alkoxy, halo-substituted Cm alkoxy and NH?, (b) a 6-membered monocyclic aromatic group selected from pyridyl, pyrazinyl, pyrimidinyl and pyridazinyl, and said monocyclic armomatic group being optionally substituted with one or two substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4), (c) a 5-membered monocyclic aromatic group selected from imidazolyl, thiazolyl, furyl, thienyl, pyrrolyl, tetrazolyl, triazolyl, oxazolyl, isoxazolyl, thiadiazolyl and pyrazolyl, and said monocyclic aromatic group being optionally substituted with one or two substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4); R1 is hydrogen, methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl or tert-butyl; X is independently selected from halo, Cm alkyl, halo-substituted Cm alkyl, OH, Cm alkoxy, halo-substituted Cm alkoxy, Cm alkylthio, NO2, NH?, di-(CM alkyl)amino,
Cm alkylamino, CN, HO-(Cm) alkyl, Cm alkoxv-CiM alkyl, Cw alkylsulfonyl and aminosulfonyl; and n is 0, 1, 2, or 3.
Further preferred compounds of this invention are those of the formula (I) wherein Z is OH, methoxy, ethoxy, n-propoxy, iso-propoxy, n-butoxy, iso-butoxyor or tert-butoxy; Q is selected from the following: (a) phenyl optionally substituted with one or two substituents independently selected from (a-1) fluoro, chloro, bromo, iodo, methyl, ethyl, propyl, butyl, CH2F, CHF2, CF3, methoxy, ethoxy, n-propoxy, n-butoxy, isopropoxy, CH2F-O-, CHF2-O-, C]?3-O-, methylthio, ethylthio, hydroxymethyl, methoxymethyl, methoxyethyl, ethoxymethyl, hydroxy, nitro, methylsulfonyl, cyano, (HOffHsCfrC-, acetyl and methylsulfonylamino, (a-2) phenyl or benzyloxy, and the phenyl or phenyl moiety of benzyloxy being optionally substituted with one substituent selected from methyl, ethyl, propyl, CF3, F, Cl, OH, methoxy, ethoxy and NH2, (a-3) 5-membered monocyclic aromatic group selected from furyl, thienyl and pyrrolyl, and the 5-membered monocyclic aromatic group optionally being substitued with one substituent selected from methyl, ethyl, propyl, CF3, F, Cl, OH, methoxy, ethoxy and NH2, (a-4) pyridyl optionally substitued with one substituent selected from methyl, ethyl, propyl, CF3, F, Cl, OH, methoxy, ethoxy and NH2, (b) pyridyl optionally substituted with one, two or three substituents independently selected from the above group (a-1), (a-1), (a-2), (a-3) and (a-4), (c) imidazolyl, thiazolyl, furyl, thienyl, isoxazolyl, 1,2,3-thiadiazolyl or pyrrolyl, and said imidazolyl, thiazolyl, furyl, thienyl, isoxazolyl, 1,2,3-thiadiazolyl or pyrrolyl being optionally substituted with one or two substituents independently selected from the above group (a-1), (a-2), (a-3) and (a-4); R1 is hydrogen, methyl, ethyl, n-propyl, iso-propyl; X is independently selected from fluoro, chloro, bromo, methyl, ethyl, propyl, butyl, CH?F, CHF?, CF3, methoxy, CF3O or ethoxy; and n is 0, 1 or 2.
Further preferred compounds of this invention are those of the formula (I) wherein Z is OH, ethoxy or methoxy; Q is phenyl, chlorophenyl, fluorophenyl, bromophenyi, methylphenyl, methoxyphenyl, (furyl)phenyl, trifluoromethylphenyl, trifluoromethoxyphenyl, pyridyl, methylpyridyl, ethylpyridyl, propylpyridyl, dimethlylpyridyl, chloropyridyl, fluoropyridyl, trifluoromethylpyridyl, methoxypyridyl, (ethyl)(ethoxy)pyridyl, (chloro)(ethyl)pyridyl, thiazofyl, methylthiazolyl, furyl, methoxymethylfuryl, isoquinolyl, cyclohexyl, methoxyphenyl, (fluoro)(ethyl)pyridyl, : dimethylpyridyl or (ethoxy)(ethyl)pyridyl; R1 is hydrogen; X is fluoro, chloro, methyl, ethyl, isopropyl, tert-butyl, CF3 or methoxy; and n is 1 or 2.
Further preferred compounds of this invention are those of the formula (I) wherein ) Z is OH, ethoxy or methoxy; Q is phenyl, chlorophenyl, pyridyl, methylpyridyl, ethylpyridyl, propylpyridyl or chloropyridyl; R1 is hydrogen; X is fluoro, chloro, methyl or CF3; and n is 1 or 2.
Preferred individual compounds of this invention are: ethyl (2-benzoyl-6-chloro- lH-indol-3-yl)acetate; i (2-benzoyl-6-chloro-lH-indol-3-yl)acetic acid; (2-benzoyl-6-chloro-lH-indol-3-yl)acetlc acid, sodium salt; [6-chloro-2-(2-methylbenzoyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(3-methylbenzoyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(4-methylbenzoyl)-lH-indol-3-yl]acetic acid; ) [6-chloro-2-(3-chlorobenzoyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-chlorobenzoyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-chlorobenzoyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(3 -fluorobenzoyl)-1 H-indol-3 -yl]acetic acid; [6-chloro-2-(4-fluorobenzoyl)-lH-indol-3-yl]acetic acid; [2-(3 -bromobenzoyl)-6-chloro-1 H-indol-3 -yl] acetic acid; [2-(4-bromobenzoyl)-6-chloro-1 H-indol-3 -yl] acetic acid; [6-chloro-2-(3-trifluoromethylbenzoyl)-1 H-indol-3-yl] acetic acid; [6-chloro-2-(4-trifluoromethylbenzoyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(3,4-dichlorobenzoyl)-1 H-indol-3 -yl] acetic acid; (2-benzoyl-4-chloro-1 H-indol-3-yl)acetic acid; [5-chloro-2-(3-methylbenzoyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(4-chlorobenzoyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(3-chlorobenzoyl)-lH-indol-3-yl]acetic acid; [2-(4-chlorobenzoyl)-5-fluoro-lH-in'dol-3-yl]acetic acid; [2-(3-chlorobenzoyl)-5 -fluoro-1 H-indol-3 -yl] acetic acid; [5 -methoxy-2-(3-methylbenzoyl)-l H-indol-3 -yl] acetic acid; (2-benzoyl-7-chloro-lH-indol-3-yl)acetic acid; (2-benzoyl-4,5-dichloro-lH-indol-3-yl)acetic acid; (2-benzoyl-4,6-dichloro-lH-indol-3-yl)acetic acid; ’
(2-benzoyl-5,6-dichloro-lH-indol-3-yl)acetic acid; I
I/-2-(2-benzoyl-6-chloro-lH-mdol-3-yl)propanoic acid; J less polar antipode, 2-(2-benzoyl-6-chloro-lH-indol-3-yl)propanoic acid; more polar antipode, 2-(2-benzoyl-6-chloro-l H-indol-3 -yl)propanoic acid; [6-chloro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(5-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-chloropyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-chloropyridine-2-carbonyl)-1 H-indol-3 -yl] acetic acid; [6-chloro-2-(pyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5 -chloro-2-(6-methylpyridine-2-carbonyl)-l H-indol-3 -yl] acetate; [5-chloro-2-(6-methylpyridine-2-carbonyI)-lH-indoI-3-yl]acetic acid; [6-chloro-2-( 1 -methylimidazole-2-carbonyl)-1 H-indol-3 -yl] acetic acid; methyl [5 -chloro-2-(thiazole-2-carbonyl)-1 H-indol-3-yi]acetate; [5-chloro-2-(thiazole-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl (2-benzoyl-6-chloro-l H-indol-3-yl)acetate; (2-benzoyl-6-chloro-lH-indol-3-yl)-JV,iV-dimethylacetamide; (2-benzoyl-6-chloro-lH-indol-3-yl)-jV-methylacetamide; (2-benzoyl-6-chloro-lH-indol-3-yl)acetamide; (2-benzoyl-6-chloro-lH-indol-3-yl)-2V-methoxy-JV-methylacetamide; 2-(2-benzoyl-6-chloro-1 H-indol-3-yl)-1 -piperidino-1 -ethanone; 2-(2-benzoyl-6-chloro-1 H-indol-3 -yl)-1 -(4-methy 1-1 -piperazinyl)-1 -ethanone; (2-benzoyl-6-chloro-lH-indol-3-yl)-/V-(2-cyanoethyl)acetamide; (2-benzoyl-6-chloro-lH-indol-3-yl)-;V-(2-hydroxyethyl)acetamide; 2-(2-benzoyl-6-chloro-lH-indol-3-yl)-l-morpholino-l-ethanone; [2-(4-chlorobenzoyl)-lH-indol-3-yl]acetic acid; * [6-chloro-2-(2-ftirylcarbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(cyclohexanecarbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-methoxybenzoyl)-1 H-indol-3-yl]acetate; [6-chloro-2-(4-methoxybenzoyl)~ 1 H-indol-3 -yl] acetic acid; methyl [6-chloro-2-(4-ethylpyTidine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-ethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5 -chloro-2-(4-ethy lpyridine-2-carbonyl)-1 H-indol-3 -yl] acetate; [5-chloro-2-(4-ethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-isopropylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-isopropylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(4-isopropylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(4-isopropylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-propylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-propylpyridine-2-carbonyl)-1 H-indol-3 -yl] acetic acid; methyl [5-chloro-2-(4-propylpyridine-2-carbonyi)-lH-indol-3-yl]acetate; [5-chloro-2-(4-propylpyridine-2-carbonyl)-lH-mdol-3-yl]acetic acid; methyl [2-(4-ter/-butylpyridine-2-carbonyl)-6-chloro-lH-indol-3-yl]acetate; [2-(4-/er/-butylpyridine-2-carbonyl)-6-chloro-1 H-indol-3-yl]acetic acid; methyl [2-(4-iert-butylpyridine-2-carbonyl)-5-chloro-lH-indol-3-yl]acetate; [2-(4-terr-butylpyridine-2-carbonyl)-5-chloro-1 H-indol-3-yl] acetic acid; methyl [6-chloro-2-(3-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(3 -methylpyridine-2-carbonyl)-1 H-indol-3 -yl] acetic acid; methyl [5-chloro-2-(3-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(3-methylpyridine-2-carbonyl)-1 H-indol-3 -yl] acetic acid; methyl [6-chloro-2-(6-methylpyridine-2-carbonyl)-1 H-indol-3-yl]acetate; [6-chloro-2-(6-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(5-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(5-methylpyridine-2-carbonyl)-lH-indol-3-yljacetic acid; methyl [6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-lH-indol-3-yl]acetate; [6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-1 H-indol-3-yl]acetate; ( [5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(5-chloropyridine-2-carbonyl)-lH-indol-3-yl]acetaTe; < [5-chloro-2-(5-chloropyridine-2-carbonyl)-1 H-indol-3-yl]acetic acid; < methyl [6-chloro-2-(5-chloropyridine-2-carbonyl)-1 H-indol-3-yl]acetate; ( [6-chloro-2-(5-chloropyridine-2-carbonyl)-1 H-indol-3 -yl] acetic acid; j methyl [5-chloro-2-(4-chloropyridine-2-carbonyl)-lH-indol-3-yl]acetate; j [5-chloro-2-(4-chloropyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; 1 methyl [6-chloro-2-(pyridine-3-carbonyl)-l H-indol-3-yl]acetate; [6-chloro-2-(pyridine-3-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(pyridine-4-carbonyl)-1 H-indol-3 -yl] acetate; [6-chloro-2-(pyridine-4-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-lH-indol-3-yI]acetate; [6-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-lH-indol-3-yl]acetate; [5-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonvl]-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(3,4-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; i [5-chloro-2-(3,4-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-1 H-indol-3-yl] acetic acid; methyl [6-chloro-2-(4-methoxypyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-methoxypyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(4-methoxypyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(4-methoxypyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(3,5-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(3,5-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(3-ethoxy-4-ethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(3 -chloro-4-ethylpyridine-2-carbonyl)-1 H-indol-3 -yl] acetic acid; methyl [5-chloro-2-(3-chIoro-4-ethylpyridine-2-carbonyl)-1 H-indol-3-yl]acetate; [5-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-1 H-indol-3 -yl] acetic acid; methyl [6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5,6-dichloro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5,6-dichloro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-methyl-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-methyl-2-(4-methylpyridine-2-carbonyl)-1 H-indol-3-yl]acetic acid; methyl [5-fluoro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-fluoro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-methoxy-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-methoxy-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-methoxy-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-methoxy-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-ethyl-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-ethyl-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-ethyl-2-(4-ethylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-ethyl-2-(4-ethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-ethyl-2-(4-methylpyridine-2-carbonyl)-l H-indol-3-yl] acetate; [6-ethyl-2-(4-methylpyridine-2-carbonyl)-l H-indol-3-yl] acetic acid; methyl [5-isopropyl-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-isopropyl-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-vl]acetic acid; methyl [2-(4-methylpyridine-2-carbonyl)-6-trifluoromethyl-lH-indol-3-yl]acetate; [2-(4-methylpyridine-2-carbonyl)-6-trifluoromethyl-lH-Lndol-3-yl]acetic acid; methyl [5-iert-butyl-2-(4-methylpyridine-2-carbonyl)-lH-iri.dol-3-yl]acetate; [5-teri-butyl-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [2-(4-methyipyridine-2-carbonyl)-5-trifluoromethoxy-lH-indol-3-yl]acetate; [2-(4-methyl-2-pyridine-2-carbonyl)-5-trifluoromethoxy-1 H-indol-3-yl] acetic acid;
I methyl [2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethoxv-lH-indol-3-yl]acetate; [2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethoxy-lH-indol-3-yl]acetic acid; methyl [6-methyl-2-(4-methylpyridine-2-carbonyl)-1 H-indol-3 -yl] acetate; ’ (6-methyI-2-(4-methylpyridine-2-carbonyl)-1 H-indol-3-yl]acetic acid; methyl [2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-1 H-indol-3-yl]acetate; j [2-(4-methylpyridine-2-carbonyl)-5-trifluoromethyl-lH-indol-3-yl]acetic acid; j methyl [2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-lH-indol-3-yl]acetate; [2-(4-ethylpyridine-2-carbonyl)-5-trifluoromethyl-lH-indol-3-yl]acetic acid; methyl (2-benzoyl-1 H-indol-3-yl)acetate; (2-benzoyl-lH-indol-3-yl)acetic acid; methyl [2-(4-chlorobenzoyl)-6-methyl-lH-indol-3-yl]acetate; [2-(4-chlorobenzoyl)-6-methyl-lH-indol-3-yl]acetic acid; [2-(4-chlorobenzoyl)-5-methyl-lH-indol-3-yl]acetic acid; methyl [6-methoxy-2-(4-chlorobenzoyl)-lH-indol-3-yl] acetate; [6-methoxy-2-(4-chlorobenzoyl)-lH-indol-3-yl] acetic acid; [2-(4-chlorobenzoyl)-6-trifluoromethyl-1 H-indol-3 -yl] acetic acid; methyl [2-(4-chlorobenzoyl)-5-ethyl-lH-indol-3-yl]acetate; [2-(4-chlorobenzoyl)-5 -ethyl-1 H-indol-3 -yl] acetic acid; methyl [2-(4-chlorobenzoyl)-5-methoxy-lH-indol-3-yl]acetate; [2-(4-chlorobenzoyl)-5-methoxy-lH-indol-3-yl]acetic acid; methyl [2-(4-chlorobenzoyl)-5-isopropyl-lH-indol-3-yl]acetate; [2-(4-chlorobenzoyl)-5-isopropyl-lH-indol-3-yl]acetic acid; methyl [2-(4-chlorobenzoyl)-5-trifluoromethyl-lH-indol-3-yl]acetate; [2-(4-chlorobenzoyl)-5-trifluoromethyl-1 H-indol-3 -yl] acetic acid; methyl [2-(4-chlorobenzoyl)-5-trifluoromethoxy-lH-indol-3-yl] acetate; [2-(4-chlorobenzoyl)-5-trifluoromethoxy-1 H-indol-3 -yl]acetic acid; methyl [6-chloro-2-(2-methoxybenzoyl)-1 H-indol-3 -yl] acetate; [6-chloro-2-(2-methoxybenzoyl)-1 H-indol-3-yl] acetic acid; methyl [6-chloro-2-(3-methoxybenzoyl)-lH-indol-3-yl]acetate; [6-chloro-2-(3 -methoxybenzoyl)-1 H-indol-3 -yl] acetic acid; methyl [6-chloro-2-(3-benzyloxybenzoyl)-lH-indol-3-yl]acetate; [6-chloro-2-(3 -benzyloxybenzoyl)-1 H-indol-3 -yl] acetic acid; methyl [6-chloro-2-(3 -hydroxybenzoyl)-1 H-indol-3 -yl] acetate; [6-chloro-2-(3-hydroxybenzoyl)-1 H-indol-3-yl] acetic acid; methyl [6-chloro-2-(4-benzoxybenzyloyl)-1 H-indol-3 -yl] acetate; [6-chloro-2-(4-benzyloxybenzoyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-hydroxybenzoyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-hydroxybenzoyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-isopropoxybenzoyl)-1 H-indol-3-yl]acetate; [6-chloro-2-(4-isopropoxybenzoyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-phenylbenzoyl)-lH-indoI-3-yl]acetate; [6-chloro-2-(4-phenylbenzoyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-trifluoromethoxybenzoyl)-1 H-indol-3 -yl] acetate; [6-chloro-2-(4-trifluoromethoxybenzoyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(4-trifluoromethoxybenzoyl)-lH-indol-3-yl]acetate; [5 -chloro-2-(4-trifluoromethoxybenzoyl)-1 H-indol-3 -yl] acetic acid; methyl [5-chloro-2-(4-methoxybenzoyl)-lH-indol-3-yl]acetate; [5-chloro-2-(4-methoxybenzoyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-nitrobenzoyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-nitrobenzoyl)-1 H-indol-3 -yl] acetic acid; methyl [6-chloro-2-[(4-methylsulfonyl)benzoyl]-lH-indol-3-yl]acetate; [6-chIoro-2-[(4-methylsulfonyI)benzoyI]-lH-indol-3-yI]acetic acid; methyl [6-chloro-2- [4-(methylsulfonylamino)benzoyl] -1 H-indol-3 -yl] acetate; [6-chloro-2- [4-(methylsulfonylamino)benzoyl] -1 H-indol-3 -yl] acetic acid; [6-chloro-2-(2-chlorobenzoyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(2,4-dichlorobenzoyl)-lH-indol-3-yl]acetic acid; methyl [6-chIoro-2-(4-chloro-3-fluorobenzoyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-chloro-3 -fluorobenzoyl)-1 H-indol-3 -yl] acetic acid; methyl [6-chloro-2-(4-cyanobenzoyl)-lH-indol-3-yl]acetate; methyl [6-chloro-2-[4-bromobenzoyl]-lH-indol-3-yl]acetate; methyl [6-chloro-2- [4-(2-thienvl)benzoyl]-1 H-indol-3 -yl] acetate; h [6-chloro-2-[4-(2-thienyl)benzoyl]-lH-indol-3-yl]acetic acid; ¢. methyl [6-chloro-2-[4-(2-furyl)benzoyl]-lH-indol-3-yl]acetate; * [6-chloro-2-[4-(2-furyl)benzoyl]-l H-indol-3-yl] acetic acid; methyl [6-chloro-2-[4-(3-pyridyl)benzoyl]-lH-indol-3-yl]acetate; "
C
[6-chloro-2-[4-(3-pyridyl)benzoyl]-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-[4-(2-thiazolyl)benzoyl]-lH-indol-3-yl]acetate; ε [6-chloro-2-[4-(2-thiazolyl)benzoyl]-lH-indol-3-yl]acetic acid; £ methyl [6-chloro-2-(3-bromobenzoyl)-lH-indol-3-yl]acetate; < methyl [6-chloro-2- [3 -(2-furyl)benzoyl]-1 H-indol-3 -yl] acetate; [6-chloro-2- [3 -(2-furyl)benzoyl] -1 H-indol-3 -yl] acetic acid; methyl dl-2-[6-chloro-2-(4-chlorobenzoyl)-1 H-indol-3 -yl] propionate; dl-2-[2-(4-chlorobenzoyl)-6-chloro-1 H-indol-3 -yl]propionic acid; methyl [5-chloro-2-(isoquinoline-3-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(isoquinoline-3-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chIoro-2-(isoquinoline-3-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(isoquinoline-3 -carbonyl)-1 H-indol-3 -yl] acetic acid; methyl [5-chloro-2-(5-methylisoxazole-3-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(5-methylisoxazole-3-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(5-methylisoxazole-3 -carbonyl)-1 H-indol- 3-yl] acetate; [6-chloro-2-(5-methylisoxazole-3-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(4-methyl-l,2,3-thiadiazole-5-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(4-methyl-l,2,3-thiadiazole-5-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-methyl-l,2,3-thiadiazole-5-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-methyl-l,2,3-thiadiazole-5-carbonyl)-lH-indoI-3-yl]acetic acid; methyl [5-chloro-2-(5-methylthiazole-2-carbonyl)-l H-indol-3-yl]acetate; (5-chloro-2-(5-methylthiazole-2-carbonyl)-l H-indol-3 -yl] acetic acid; methyl [6-chloro-2-(5-methylthiazole-2-caxbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(5-methylthiazole-2-carbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(2-thienyl)carbonylindol-3-yl]acetic acid; methyl [6-chloro-2-[3-(l-hydroxy-l-methylethyl)-2-furoyl]-lH-indol-3-yl]acetate; [6-chloro-2 -(3-(1 -hydroxy-1 -methylethyl)-2-furoy 1] -1 H-indol-3 -yl] aceti c acid; methyl [6-chloro-2-[3-methoxymethyl-2-furoyl]-lH-indol-3-vl]acetate; [6-chloro-2-[3-methoxymethyl-2-furoyl]-lH-indol-3-yl]acetic acid; [6-chloro-2-(l-methylimidazole-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-( 1 -methylimidazole-2-carbonyl)-1 H-indol-3 -yl] acetate; methyl [5-chloro-2-( 1 -methylimidazole-2-carbonyl)-l H-indol-3-yl]acetate; [5-cloro-2(l-methylimidazole-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(imidazole-2-carbonyl)-lH-indol-3-yl]acetate; [5-cloro-2-(imidazole-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(imidazole-2-carbonyl)-1 H-indol-3-yl] acetate; [6-cloro-2-(imidazole-2-carbonyl)-1 H-indol-3 -yl] acetic acid; methyl [5-chloro-2-(4-methylthiazole-2-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(4-methylthiazole-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(l-methylpyrrole-2-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-( 1 -methylpyrrole-2-carbonyl)-1 H-indo 1-3-yl]aceti c acid; methyl [5-chloro-2-(2-methylimidazole-4-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(2-methylimidazole-4-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(thiazole-5-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(thiazole-5-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-methylthiazole-2-carbonyl)-1 H-indol-3 -yl] acetate; [6-chloro-2-(4-methylthiazole-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-[3-(ethoxycaronyl)isoxazole-5-carbonyl]-lH-indol-3-yl]acetate; [5-chloro-2-[3-(carboxy)isoxazole-5-carbonyl]-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-cyclopropanecarbonyl-lH-indol-3-yl]acetate; [6-chloro-2-cyclopropanecarbonyl-l H-indol-3 -yl] acetic acid; methyl [6-chloro-2-cvclobutanecarbonyl-1 H-indol-3 -yl] acetate; [6-chloro-2-cyclobutanecarbonyl-lH-indol-3-yl]acetic acid; methyl [5-(terf-butyl)-2-(4-chlorobenzoyl)-lH-indol-3-yl] acetate; [5-(tert-butyl)-2-(4-chlorobenzoyl)-l H-indol-3-yl] acetic acid; [6-chloro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]-.V,A-dimethylacetamide; [6-chloro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]-N-methylacetamide; [5-chloro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]-N-(2-hydroxy§thyl)acetamid 1 e; [5-chloro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]-N-methoxyacetamide;
I 2- [5-chloro-2-(4-methylpyridine-2-carbonyl)-1 H-indol-3 -vl] -1 -piperazinyl-1 -ethanone; [5-chloro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]-N-(2-aminoethyl)acetamide; ' 2- [5 -chloro-2-(4-methylpyridine-2-carbonyl)-1 H-indol-3-yl] -1 -(3-amino-1 -pyrrolidinyl )-1-ethanone; [6-chloro-2-(4-chlorobenzoyl)-5-fluoro-lH-indol-3-yl]acetic acid; , methyl [6-chloro-5-fluoro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-5-fluoro-2-(4-methylpyridine-2-carbonyl)-lH-indoI-3-yl]acetic acid; methyl [6-chloro-2-[4-(l-hydroxyethyl)pyridine-2-carbonvl]-lH-indol-3-yl]acetate; [6-chloro-2-[4-(l-hydroxyethyl)pyridine-2-carbonyl]-lH-indol-3-yl]acetic acid; [6-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(2-nitrobenzoyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(2,4-dimethoxybenzoyl)-1 H-indol-3 -yl] acetic acid; [6-chloro-2-(4-diftiluoromethoxybenzoyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(2,5-dimethoxybenzoyl)-lH-indol-3-yl]acetic acid; methyl [5-acetyl-2-(4-chlorobenzoyl)-1 H-indol-3 -yl] acetate; [5 -acetyl-2-(4-chlorobenzoyl)-1 H-indol-3 -yl] acetic acid; methyl [6-chloro-2-(4-chlorobenzoyl)-5-fluoro-lH-indol-3-yl]acetate; methyl [6-fluoro-2-(4-methylpridine-2-carbonyl]-l H-indol-3-yl] acetate; [6-fluoro-2-(4-methylpridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-fluoro-2-(4-chlorobenzoyl)-lH-indol-3-yl] acetate; [6-fluoro-2-(4-chlorobenzoyl) -1 H-indol-3-yl]acetic acid; [2-(4-methylpyridine-2-carbonyl)-5-methylthio-lH-indoi-3-yl]acetic acid; [2-(4-methylpyridine-2-carbony 1)-5-methylthio-1 H-indol-3-vl] acetic acid, and a salt thereof.
Preferred individual compounds of this invention are: ethyl (2-benzoyl-6-chloro-lH-indol-3-yl)acetate; (2-benzoyl-6-chloro-lH-indol-3-yl)acetic acid; (2-benzoyl-6-chloro-lH-indol-3-yl)acetic acid, sodium salt; [6-chloro-2-(2-methylbenzoyl)~ 1 H-indol-3 -yl] acetic acid; [6-chloro-2-(3-methylbenzoyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(4-methylbenzoyl)-1 H-indol-3 -yl] acetic acid; [6-chloro-2-(3-chlorobenzoyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-chlorobenzoyl)-1 H-indol-3 -yl] acetate; [6-chloro-2-(4-chlorobenzoyl)-l H-indol-3 -yl] acetic acid; [6-chloro-2-(3 -fluorobenzoyl)-1 H-indol-3 -yl] acetic acid; [6-chloro-2-(4-fluorobenzoyl)-1 H-indo 1-3 -yl] acetic acid; [2-(3 -bromobenzoyl)-6-chloro-1 H-indol-3 -yl] acetic acid; [2-(4-bromobenzoyl)-6-chloro-1 H-indol-3-yl]acetic acid; [6-chloro-2-(3-trifluoromethylbenzoyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(4-trifluoromethylbenzoyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(3,4-dichlorobenzoyl)-lH-indol-3-yl]acetic acid; (2-benzoyl-4-chloro-lH-indol-3-yl)acetic acid; [5-chloro-2-(3-methylbenzoyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(4-chlorobenzoyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(3-chlorobenzoyl)-lH-indol-3-yl]acetic acid; [2-(4-chlorobenzoyl)-5-fluoro-1 H-indol-3-yl]acetic acid; [2-(3-chlorobenzoyl)-5-fluoro-lH-indol-3-yl]acetic acid; [5-methoxy-2-(3-methylbenzoyl)-lH-indol-3-yl]acetic acid; (2-benzoyl-7-chloro-l H-indol-3-yl)acetic acid; (2-benzoyl-4,5-dichloro-lH-indol-3-yl)acetic acid; (2-benzoyl-4,6-dichloro-1 H-indol-3 -yl)acetic acid; (2-benzoyl-5,6-dichloro-lH-indol-3-yl)acetic acid; riZ-2-(2-benzoyl-6-chloro-1 H-indol-3-yl)propanoic acid; less polar antipode, 2-(2-benzoyl-6-chloro-lH-indol-3-yl)propanoic acid; more polar antipode, 2-(2-benzoyl-6-chloro-l H-indol-3-yl)propanoic acid; [6-chloro-2-(4-methylpyridine-2-carbonyl)-1 H-indol-3-yl] acetic acid; [6-chloro-2-(5-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [6-chloro-2-(4-chloropyridine-2-carbonyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-chloropyridine-2-carbonyl)-1 H-indol-3 -yl] acetic acid; [6-chloro-2-(pyridine-2-carbonyl)-l H-indol-3 -yl] acetic acid; * [5-chloro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; methyl [5-chloro-2-(6-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetate; [5-chloro-2-(6-methylpyridine-2-carbonyl)-1 H-indol-3 -yl] acetic acid; [6-chloro-2-( 1 -methylimidazole-2-carbonyl)-1 H-indol-3 -yl] acetic acid; , methyl [5-chloro-2-(thiazole-2-carbonyl)-l H-indol-3-yl] acetate; <
[5-chloro-2-(thiazole-2-carbonyl)-lH-indol-3-yl]acetic acid; I
methyl (2-benzoyl-6-chloro-lH-indol-3-yl)acetate; I
[2-(4-chlorobenzoyl)-1 H-indol-3-yl] acetic acid; [6-chloro-2-(2-furylcarbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(cyclohexanecarbonyl)-1 H-indol-3 -yl] acetic acid; methyl [6-chloro-2-(4-methoxybenzoyl)-lH-indol-3-yl]acetate; [6-chloro-2-(4-methoxybenzoyl)-1 H-indol-3 -yl] acetic acid; methyl [6-chloro-2-(4-ethylpyridine-2-carbonyl)-l H-indol-3 -yl]acetate; [6-chloro-2-(4-ethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(4-ethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(4-isopropylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(4-isopropylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(4-propylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(4-propylpyridine-2-carbonyl)-l H-indol-3-yl]acetic acid; [2-(4-feri-butylpyridine-2-carbonyl)-6-chloro-lH-indol-3-yl]acetic acid; [2-(4-terr-butylpyridine-2-carbonyi)-5-chloro-1 H-indol-3-yl] acetic acid; [6-chloro-2-(3-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(3-methylpyridine-2-carbonyl)- lH-indol-3-yl]acetic acid; [6-chloro-2-(6-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(5-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-lH-indol-3-yl]acetic acid; [5-chloro-2-[5-(trifluoromethyl)pyridine-2-carbonyl]-lH-indol-3-yl]acetic acid; ) [5-chloro-2-(5-chloropyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(5-chloropyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(4-chloropyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(pyridine-3-carbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(pyridine-4-carbonyl)-lH-indol-3-yl]acetic acid; i [6-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-lH-indol-3-yl]acetic acid; [5-chloro-2-[4-(hydroxymethyl)pyridine-2-carbonyl]-lH-indol-3-yl]acetic acid; [5-chloro-2-(3,4-dinaethylpyridine-2-carbonyl)-1 H-indol-3 -yl] acetic acid; [5-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(4,5-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; ) [6-chloro-2-(4-methoxypyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(4-methoxypyridine-2-carbonyl)-l H-indol-3-yl]acetic acid; [6-chloro-2-(3,5-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(4-ethyl-3-fluoropyridine-2-carbonyl)-l H-indol-3 -yl] acetic acid; [6-chloro-2-(3 -ethoxy-4-ethylpyridine-2 -carbonyl)-1 H-indol-3 -yl] acetic acid; > [6-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-1 H-indol-3 -yljacetic acid; [5-chloro-2-(3-chloro-4-ethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [5-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [6-chloro-2-(4,6-dimethylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; [5,6-dichloro-2-(4-methylpyridine-2-carbonyl)-lH-indol-3-yl]acetic acid; ) [5-methyl-2-(4-methylpyridine-2-carbonyl)-1 H-indol-3 -yl] acetic acid; [5-fluoro-2-(4-methylpyridine-2-carbonyl)-1 H-indol-3-yl]acetic acid;

Claims (1)

  1. Original document published without claims.
APAP/P/1998/001423A 1998-01-05 1998-12-17 2,3-Substituted indole compounds as anti-inflammatory and analgesic agents. AP869A (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
IB9800003 1998-01-05

Publications (2)

Publication Number Publication Date
AP9801423A0 AP9801423A0 (en) 1998-12-31
AP869A true AP869A (en) 2000-09-04

Family

ID=11004645

Family Applications (1)

Application Number Title Priority Date Filing Date
APAP/P/1998/001423A AP869A (en) 1998-01-05 1998-12-17 2,3-Substituted indole compounds as anti-inflammatory and analgesic agents.

Country Status (39)

Country Link
US (1) US6608070B1 (en)
EP (1) EP1045833B1 (en)
JP (1) JP3347136B2 (en)
KR (1) KR100404054B1 (en)
CN (1) CN1284064A (en)
AP (1) AP869A (en)
AR (1) AR016977A1 (en)
AT (1) ATE308519T1 (en)
AU (1) AU748107B2 (en)
BG (1) BG104643A (en)
BR (1) BR9813124A (en)
CA (1) CA2316863A1 (en)
CO (1) CO4970807A1 (en)
DE (1) DE69832200T2 (en)
DZ (1) DZ2700A1 (en)
EA (1) EA200000614A1 (en)
ES (1) ES2255190T3 (en)
GT (1) GT199800205A (en)
HN (1) HN1997000098A (en)
HR (1) HRP20000454A2 (en)
HU (1) HUP0102922A3 (en)
ID (1) ID24876A (en)
IL (1) IL136885A0 (en)
IS (1) IS5532A (en)
MA (1) MA24736A1 (en)
NO (1) NO20003451L (en)
OA (1) OA11441A (en)
PA (1) PA8466201A1 (en)
PE (1) PE20000055A1 (en)
PL (1) PL341696A1 (en)
SA (1) SA99191299A (en)
SK (1) SK9912000A3 (en)
TN (1) TNSN99001A1 (en)
TR (1) TR200001906T2 (en)
TW (1) TW436482B (en)
UY (2) UY25332A1 (en)
WO (1) WO1999035130A1 (en)
YU (1) YU41600A (en)
ZA (1) ZA9911B (en)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6555540B1 (en) * 1999-06-30 2003-04-29 Pfizer Inc Combinations of aldose reductase inhibitors and selective cyclooxygenase-2 inhibitors
MXPA00006605A (en) * 1999-07-02 2004-12-09 Pfizer Bicycliccarbonyl indole compounds as anti-inflammatory/analgesic agents.
EP1065206B1 (en) * 1999-07-02 2002-10-09 Pfizer Inc. Tetrazolylalkyl indole compounds as anti-inflammatory and analgesic agents
DE60016191T2 (en) 1999-12-08 2005-12-22 Pharmacia Corp., Chicago CYCLOOXYGENASE-2 INHIBITORY COMPOSITIONS WITH FAST ACTION INTRUSION
EP1572678A4 (en) * 2002-12-19 2008-05-07 Elan Pharm Inc Substituted n-phenyl sulfonamide bradykinin antagonists
US7223785B2 (en) 2003-01-22 2007-05-29 Boehringer Ingelheim International Gmbh Viral polymerase inhibitors
US7098231B2 (en) 2003-01-22 2006-08-29 Boehringer Ingelheim International Gmbh Viral polymerase inhibitors
EP1534305B9 (en) 2003-05-07 2007-03-07 Osteologix A/S Treating cartilage / bone conditions with water-soluble strontium salts
KR100795462B1 (en) 2006-09-27 2008-01-16 한국생명공학연구원 Indole derivatives, preparation methods thereof, and pharmaceutical compositions for the prevention and treatment of metabolic diseases containing the same as active ingredients
CN101611016B (en) 2006-10-17 2012-01-25 斯蒂菲尔实验室公司 Talarazole metabolites
US20120022121A1 (en) * 2007-11-29 2012-01-26 Dalton James T Indoles, derivatives and analogs thereof and uses therefor
US8937182B2 (en) 2010-04-19 2015-01-20 Metabolic Solutions Development Company, Llc Synthesis for thiazolidinedione compounds
WO2012006477A1 (en) 2010-07-07 2012-01-12 Ardelyx, Inc. Compounds and methods for inhibiting phosphate transport
EP2590656B1 (en) 2010-07-07 2017-11-15 Ardelyx, Inc. Compounds and methods for inhibiting phosphate transport
EP2590655B1 (en) 2010-07-07 2015-06-24 Ardelyx, Inc. Compounds and methods for inhibiting phosphate transport
EP2590965B1 (en) 2010-07-07 2016-04-20 Ardelyx, Inc. Compounds and methods for inhibiting phosphate transport
CA2807815C (en) 2010-08-10 2018-10-02 Metabolic Solutions Development Company, Llc Novel synthesis for thiazolidinedione compounds
US8933240B2 (en) 2010-08-10 2015-01-13 Metabolic Solutions Development Company, Llc Synthesis for thiazolidinedione compounds
WO2013138600A1 (en) * 2012-03-16 2013-09-19 Rosen Eliot M Radioprotector compounds
US9808443B1 (en) 2016-11-28 2017-11-07 King Saud University Cyclooxygenase inhibitors
CN111004121A (en) * 2019-12-09 2020-04-14 南京杰运医药科技有限公司 Preparation method of 4-alkoxy acetoacetic ester compound
CN112409281B (en) * 2020-08-20 2022-11-18 上海大学 Synthetic method of (E)-3-(3-chloro-2-fluoro-6-(1H-tetrazol-1-yl)phenyl)acrylic acid
WO2022195579A1 (en) 2021-03-15 2022-09-22 Saul Yedgar Hyaluronic acid-conjugated dipalmitoyl phosphatidyl ethanolamine in combination with non-steroidal anti-inflammatory drugs (nsaids) for treating or alleviating inflammatory diseases
KR20220166745A (en) * 2021-06-10 2022-12-19 주식회사 아보메드 Novel compound with pendrin inhibitory activity and medical use thereof
CN116262721A (en) * 2023-01-12 2023-06-16 浙江师范大学 A kind of preparation method and product of indoline derivative and indole derivative

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5510368A (en) * 1995-05-22 1996-04-23 Merck Frosst Canada, Inc. N-benzyl-3-indoleacetic acids as antiinflammatory drugs
WO1996037469A1 (en) * 1995-05-22 1996-11-28 Merck Frosst Canada Inc. N-benzylindol-3-yl propanic acid derivatives as cyclooxygenase-2 inhibitors

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CO5190664A1 (en) * 1999-06-30 2002-08-29 Pfizer Prod Inc COMBINATION THERAPY FOR THE TREATMENT OF MIGRANA ADMINISTRATION OF A 5HT RECEPTOR, CAFFEINE AND A CYCLLOXYGENASA-2 INHIBITOR

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5510368A (en) * 1995-05-22 1996-04-23 Merck Frosst Canada, Inc. N-benzyl-3-indoleacetic acids as antiinflammatory drugs
WO1996037469A1 (en) * 1995-05-22 1996-11-28 Merck Frosst Canada Inc. N-benzylindol-3-yl propanic acid derivatives as cyclooxygenase-2 inhibitors

Also Published As

Publication number Publication date
UY25332A1 (en) 2001-01-31
NO20003451L (en) 2000-09-01
DE69832200T2 (en) 2006-04-20
US6608070B1 (en) 2003-08-19
SK9912000A3 (en) 2001-11-06
EP1045833B1 (en) 2005-11-02
IS5532A (en) 2000-06-13
JP2002500217A (en) 2002-01-08
KR20010033859A (en) 2001-04-25
BG104643A (en) 2001-02-28
TNSN99001A1 (en) 2005-11-10
ATE308519T1 (en) 2005-11-15
EP1045833A1 (en) 2000-10-25
NO20003451D0 (en) 2000-07-04
JP3347136B2 (en) 2002-11-20
AP9801423A0 (en) 1998-12-31
OA11441A (en) 2004-04-27
UY25590A1 (en) 1999-09-27
HRP20000454A2 (en) 2001-04-30
ES2255190T3 (en) 2006-06-16
WO1999035130A1 (en) 1999-07-15
DE69832200D1 (en) 2005-12-08
AU1500599A (en) 1999-07-26
PL341696A1 (en) 2001-04-23
IL136885A0 (en) 2001-06-14
YU41600A (en) 2003-08-29
BR9813124A (en) 2000-10-10
ID24876A (en) 2000-08-31
CO4970807A1 (en) 2000-11-07
KR100404054B1 (en) 2003-11-01
HN1997000098A (en) 1998-12-28
ZA9911B (en) 2000-07-04
TW436482B (en) 2001-05-28
EA200000614A1 (en) 2001-02-26
PA8466201A1 (en) 2000-09-29
AR016977A1 (en) 2001-08-01
AU748107B2 (en) 2002-05-30
MA24736A1 (en) 1999-10-01
SA99191299A (en) 2005-12-03
TR200001906T2 (en) 2001-01-22
CA2316863A1 (en) 1999-07-15
GT199800205A (en) 2000-06-21
DZ2700A1 (en) 2003-09-01
HUP0102922A2 (en) 2001-12-28
CN1284064A (en) 2001-02-14
PE20000055A1 (en) 2000-02-08
HUP0102922A3 (en) 2003-06-30

Similar Documents

Publication Publication Date Title
AP869A (en) 2,3-Substituted indole compounds as anti-inflammatory and analgesic agents.
ZA200007076B (en) A pharmaceutical combination comprising a COX-2 inhibitor and iNOS inhibitor.
Ansari et al. Biologically active pyrazole derivatives
Baumann et al. An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals
JP3267635B2 (en) Indole compounds as COX-2 inhibitors
CA2456817A1 (en) Alkyne-aryl-naphthyridin-4 (1h)-one derivatives as type iv phosphodiesterase inhibitor
JP4786846B2 (en) 5-Aryl-1H-1,2,4-triazole compounds which are inhibitors of cyclooxygenase-2 and pharmaceutical compositions containing the same
NO20084496L (en) Pyridyl and pyrimidinyl substituted pyrrole, thiophene and furan derivatives as kinase inhibitors
CA2583217A1 (en) 1,3,4-thiadiazole compounds as protein kinase inhibitors
CZ20001272A3 (en) Novel combination
RU2011147181A (en) ASETIDINYLDIAMIDES AS MONOACYGLYCERINE LIPASE INHIBITORS
WO2001074771A1 (en) Pyrrole-2,5-dione derivatives for the treatment of diabetes
WO2002051442A1 (en) Concomitant drugs
WO2008130879A3 (en) Tetrahydroindole and tetrahydroindazole derivatives
Saini et al. Recent advances in anti-inflammatory potential of pyridazinone derivatives
JP2010540666A5 (en)
Sharma et al. A therapeutic journey of 5-pyrazolones as a versatile scaffold: a review
KR20040099400A (en) New heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in medicine
WO2003070728A3 (en) Azabicyclo-substituted benzoylamides and thioamides for treatment of cns-related disorders
CA2483162A1 (en) Use of 3-substituted amino-1h-indole-2-carboxylic acid and 3-substituted amino benzo[b]thiophene-2-carboxylic acid derivatives as il-4 inhibitors
JP2016501254A5 (en)
CA2594667A1 (en) Compositions and therapeutic methods utilizing a combination of a 5-ht1f inhibitor and an nsaid
Asif General study of pyridazine compounds against cyclooxygenase enzyme and their relation with analgesic, anti-inflammatory and anti-arthritic activities
CA2562219A1 (en) Active substance combination comprising a carbinol combined to at least an nsaid
JP2007297385A (en) Veterinary methods and compositions