CN104684906B - Nampt inhibitor - Google Patents
Nampt inhibitor Download PDFInfo
- Publication number
- CN104684906B CN104684906B CN201380036899.6A CN201380036899A CN104684906B CN 104684906 B CN104684906 B CN 104684906B CN 201380036899 A CN201380036899 A CN 201380036899A CN 104684906 B CN104684906 B CN 104684906B
- Authority
- CN
- China
- Prior art keywords
- phenyl
- azetidine
- pyridin
- formamides
- bases
- Prior art date
- Legal status (The legal status 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 status listed.)
- Expired - Fee Related
Links
- 108010064862 Nicotinamide phosphoribosyltransferase Proteins 0.000 title abstract description 28
- 102100033223 Nicotinamide phosphoribosyltransferase Human genes 0.000 title description 26
- 239000003112 inhibitor Substances 0.000 title description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 62
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 239000000203 mixture Substances 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 489
- -1 heterocyclic radical Chemical class 0.000 claims description 444
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 363
- 125000000217 alkyl group Chemical group 0.000 claims description 282
- 229910003204 NH2 Inorganic materials 0.000 claims description 272
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 270
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 264
- 150000002118 epoxides Chemical class 0.000 claims description 264
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 239
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 226
- 238000006467 substitution reaction Methods 0.000 claims description 210
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 170
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 159
- 229910052731 fluorine Inorganic materials 0.000 claims description 154
- 239000000460 chlorine Substances 0.000 claims description 143
- 229910052801 chlorine Inorganic materials 0.000 claims description 142
- PVXOUGHWLCBJOW-UHFFFAOYSA-N azetidine-1-carboxamide Chemical class NC(=O)N1CCC1 PVXOUGHWLCBJOW-UHFFFAOYSA-N 0.000 claims description 141
- 125000003118 aryl group Chemical group 0.000 claims description 137
- 229910052740 iodine Inorganic materials 0.000 claims description 136
- 125000003342 alkenyl group Chemical group 0.000 claims description 135
- 125000000304 alkynyl group Chemical group 0.000 claims description 135
- 229910052794 bromium Inorganic materials 0.000 claims description 135
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 115
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 108
- WYURNTSHIVDZCO-UHFFFAOYSA-N tetrahydrofuran Substances C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 102
- 230000037429 base substitution Effects 0.000 claims description 100
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 88
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 87
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 84
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 83
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 76
- OTXBWGUYZNKPMG-UHFFFAOYSA-N isofulminic acid Chemical compound O[N+]#[C-] OTXBWGUYZNKPMG-UHFFFAOYSA-N 0.000 claims description 74
- 150000001408 amides Chemical class 0.000 claims description 68
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 60
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 54
- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 51
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 45
- 125000003545 alkoxy group Chemical group 0.000 claims description 44
- 229910052739 hydrogen Inorganic materials 0.000 claims description 44
- 239000001257 hydrogen Substances 0.000 claims description 44
- PBMFSQRYOILNGV-UHFFFAOYSA-N pyridazine Chemical compound C1=CC=NN=C1 PBMFSQRYOILNGV-UHFFFAOYSA-N 0.000 claims description 44
- UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 39
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 38
- 229910052799 carbon Inorganic materials 0.000 claims description 34
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 33
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 30
- 125000000623 heterocyclic group Chemical group 0.000 claims description 28
- 150000002240 furans Chemical class 0.000 claims description 27
- 150000003839 salts Chemical class 0.000 claims description 26
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 25
- 125000004122 cyclic group Chemical group 0.000 claims description 21
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims description 20
- QENGPZGAWFQWCZ-UHFFFAOYSA-N 3-Methylthiophene Chemical compound CC=1C=CSC=1 QENGPZGAWFQWCZ-UHFFFAOYSA-N 0.000 claims description 18
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 16
- 239000011737 fluorine Substances 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
- 229930192474 thiophene Natural products 0.000 claims description 16
- 235000019253 formic acid Nutrition 0.000 claims description 15
- YXTROGRGRSPWKL-UHFFFAOYSA-N 1-benzoylpiperidine Chemical compound C=1C=CC=CC=1C(=O)N1CCCCC1 YXTROGRGRSPWKL-UHFFFAOYSA-N 0.000 claims description 14
- 125000001188 haloalkyl group Chemical group 0.000 claims description 13
- AYDQIZKZTQHYIY-UHFFFAOYSA-N OC(=O)C1(C)CC(C(O)=O)=CC=C1 Chemical compound OC(=O)C1(C)CC(C(O)=O)=CC=C1 AYDQIZKZTQHYIY-UHFFFAOYSA-N 0.000 claims description 12
- 150000003053 piperidines Chemical class 0.000 claims description 12
- 229910052760 oxygen Inorganic materials 0.000 claims description 11
- 239000001301 oxygen Substances 0.000 claims description 11
- KDISMIMTGUMORD-UHFFFAOYSA-N 1-acetylpiperidine Chemical compound CC(=O)N1CCCCC1 KDISMIMTGUMORD-UHFFFAOYSA-N 0.000 claims description 10
- 150000003233 pyrroles Chemical class 0.000 claims description 10
- GZXDOXSIKJNUEW-UHFFFAOYSA-N 5-methylthiophene Chemical compound CC1=C=C[CH]S1 GZXDOXSIKJNUEW-UHFFFAOYSA-N 0.000 claims description 9
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical class C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 9
- 125000002252 acyl group Chemical group 0.000 claims description 9
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- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 9
- 150000003235 pyrrolidines Chemical class 0.000 claims description 9
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 8
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 claims description 8
- 125000006639 cyclohexyl carbonyl group Chemical group 0.000 claims description 7
- 125000006638 cyclopentyl carbonyl group Chemical group 0.000 claims description 7
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 claims description 7
- MEKCGWCEPSGOQW-UHFFFAOYSA-N 1-(azetidin-1-yl)pentan-1-one Chemical compound CCCCC(=O)N1CCC1 MEKCGWCEPSGOQW-UHFFFAOYSA-N 0.000 claims description 6
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 claims description 6
- PVMNPAUTCMBOMO-UHFFFAOYSA-N 4-chloropyridine Chemical compound ClC1=CC=NC=C1 PVMNPAUTCMBOMO-UHFFFAOYSA-N 0.000 claims description 6
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 claims description 6
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 6
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 5
- AXWLKJWVMMAXBD-UHFFFAOYSA-N 1-butylpiperidine Chemical compound CCCCN1CCCCC1 AXWLKJWVMMAXBD-UHFFFAOYSA-N 0.000 claims description 4
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 claims description 4
- 125000000070 5-oxo-L-proline group Chemical group [H]N1[C@@](C(=O)[*])([H])C([H])([H])C([H])([H])C1=O 0.000 claims description 4
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
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- WKGHUAZJNBXABN-UHFFFAOYSA-N 3-bromo-2-chloro-6-methyl-5-nitropyridine Chemical compound CC1=NC(Cl)=C(Br)C=C1[N+]([O-])=O WKGHUAZJNBXABN-UHFFFAOYSA-N 0.000 claims description 3
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 claims description 3
- SIHXFQDBQGKMHX-UHFFFAOYSA-N azetidin-1-yl(phenyl)methanone Chemical compound C=1C=CC=CC=1C(=O)N1CCC1 SIHXFQDBQGKMHX-UHFFFAOYSA-N 0.000 claims description 3
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- NYEQHQXNUPNTDV-UHFFFAOYSA-N 1-(cyclohexylmethyl)azetidine Chemical compound C1CCN1CC1CCCCC1 NYEQHQXNUPNTDV-UHFFFAOYSA-N 0.000 claims description 2
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Abstract
The method for disclosing compound, the composition comprising the compound and the treatment disease of expression NAMPT during disease for suppressing NAMPT activity.
Description
This application claims the U.S.Provisional Serial No. 61/645685,2012 10 that on May 11st, 2012 submits to
The U.S. Provisional Application that the U.S.Provisional Serial No. 61/719008 and on March 13rd, 2013 that the moon 26 was submitted to are submitted to
The priority of sequence number No. 61/779702, they are incorporated as reference.
Invention field
The present invention relates to suppress active compound, the composition comprising these compounds and the treatment of NAMPT in disease
The method of the disease of period expression NAMPT.
Background of invention
NAD+ (NADH) is in much physiologically coenzyme for playing a crucial role during necessity
(Ziegkel, M. Eur. J. Biochem. 267,1550-1564, 2000).NAD is for some signal transduction paths
It is required, including the poly- ADP- ribosylation in DNA reparations, in the signal transduction that immune system and G-protein are coupled
Single-ADP- ribosylation, and deacetylase its deacetylase activity is also required to NAD (Garten, A. et al.Trends in Endocrinology and Metabolism, 20, 130-138, 2008)。
NAMPT (also referred to as PBEF (PBEF) and Visfatin) is the phosphoric acid core for being catalyzed niacinamide
Glycosylate the enzyme of (phosphoribosylation) and be rate-limiting enzyme in one of two remedial pathways of NAD.
Increasing evidence shows that NAMPT inhibitor has as the potential of anticancer.Cancer cell has NAD higher
Basis update (turnover), and energy requirement higher is also shown compared with normal cell.In addition, in colon
Increased NAMPT expression (Van Beijnum, J.R. et al. are reported in the carcinoma of the rectumInt. J. Cancer 101, 118-
, and NAMPT participates in angiogenesis (Kim, S.R. et al. 127,2002)Biochem. Biophys. Res. Commun.
357, 150-156, 2007).The micromolecular inhibitor of NAMPT has shown that causes intracellular NAD+ levels reduction and most
Whole inducing death of neoplastic cells (Hansen, CM et al.Anticancer Res20,42111-4220,2000) and press down
Tumour growth (Olese, U.H. et al. in heteroplastic transplantation model processedMol Cancer Ther. 9, 1609-1617,
2010)。
NAMPT inhibitor also has as potential (Galli, M. et al. of inflammation and the therapeutic agent of dysbolismCancer Res.70, 8-11, 2010).For example, NAMPT is the leading enzyme in T and bone-marrow-derived lymphocyte.The selectivity of NAMPT
Suppression causes the NAD+ in lymphocyte to be lost, so as to block the extension with autoimmune disease progress, and expresses other NAD
The cell type in+generation path may no longer need.Small molecule NAMPT inhibitor (FK866) has shown that selective exclusion
Breed the Apoptosis of simultaneously induced activation T cell, and in arthritis（Collagen-Induced Arthritis）Animal model in effectively
(Busso, N. et al.Plos One3, e2267, 2008).FK866 improves EAE
(EAE)（The model of the autoimmune disorders of T cell mediation）Performance (Bruzzone, S et al.Plos One 4,
e7897, 2009).NaMPT activity improves the NF-kB transcriptional activities in human vascular endothelial, causes MMP-2 and MMP-9 to live
Change, show effect (Adya, R. of the NAMPT inhibitor in the complication of the fat and diabetes B that prevention of inflammation is mediated
Et al.Diabetes Care, 31, 758-760, 2008)。
Summary of the invention
One embodiment of the invention therefore relates to compound or its pharmaceutically acceptable salt, and it can be used as NAMPT
Inhibitor, the compound has formula (IA)
Formula (IA)；
Wherein
X1It is N and X2It is CR1；Or
X1It is CR1And X2It is N；Or
X1It is CR1And X2It is CR1；
Y1For
WhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl；
R1, every time occur when, independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxy alkyl, alkoxy,
OH、NH2、CN、NO2, F, Cl, Br and I；
R2Independently selected from C4-C6- alkyl, C4-C6- alkenyl, C4-C6- alkynyl, aryl, 3-12 circle heterocycles base, cycloalkyl and
Cycloalkenyl group；Wherein R2In C4-C6- alkyl, C4-C6- alkenyl and C4-C6- alkynyl be each independently selected by one or more from as
Under substitution base substitution：R3、OR3、SR3、S(O)R3、SO2R3、C(O)R3、CO(O)R3、OC(O)R3、OC(O)OR3、NH2、NHR3、N
(R3)2、NHC(O)R3、NR3C(O)R3、NHS(O)2R3、NR3S(O)2R3、NHC(O)OR3、NR3C(O)OR3、NHC(O)NH2、NHC
(O)NHR3、NHC(O)N(R3)2、NR3C(O)NHR3、NR3C(O)N(R3)2、C(O)NH2、C(O)NHR3、C(O)N(R3)2、C(O)
NHOH、C(O)NHOR3、C(O)NHSO2R3、C(O)NR3SO2R3、SO2NH2、SO2NHR3、SO2N(R3)2、C(O)H、C(O)OH、C
(N)NH2、C(N)NHR3、C(N)N(R3)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R2In virtue
Base, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group are each optionally independently selected by one or more from following substitution base substitution：
R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、OC(O)OR4、NH2、NHR4、N(R4)2、NHC(O)R4、
NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)OR4、NHC(O)NH2、NHC(O)NHR4、NHC(O)N
(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、C(O)N(R4)2、C(O)NHOH、C(O)NHOR4、C
(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR4、C
(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R3, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl group and heterocyclic radical；
Wherein R3In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R5、
OR5、SR5、S(O)R5、SO2R5、C(O)R5、CO(O)R5、OC(O)R5、OC(O)OR5、NH2、NHR5、N(R5)2、NHC(O)R5、NR5C
(O)R5、NHS(O)2R5、NR5S(O)2R5、NHC(O)OR5、NR5C(O)OR5、NHC(O)NH2、NHC(O)NHR5、NHC(O)N
(R5)2、NR5C(O)NHR5、NR5C(O)N(R5)2、C(O)NH2、C(O)NHR5、C(O)N(R5)2、C(O)NHOH、C(O)NHOR5、C
(O)NHSO2R5、C(O)NR5SO2R5、SO2NH2、SO2NHR5、SO2N(R5)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR5、C
(N)N(R5)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R3In aryl, cycloalkyl, cycloalkenyl group
Following substitution base substitution is each optionally independently selected by one or more from heterocyclic radical：R6、OR6、SR6、S(O)R6、SO2R6、
C(O)R6、CO(O)R6、OC(O)R6、OC(O)OR6、NH2、NHR6、N(R6)2、NHC(O)R6、NR6C(O)R6、NHS(O)2R6、NR6S
(O)2R6、NHC(O)OR6、NR6C(O)OR6、NHC(O)NH2、NHC(O)NHR6、NHC(O)N(R6)2、NR6C(O)NHR6、NR6C(O)
N(R6)2、C(O)NH2、C(O)NHR6、C(O)N(R6)2、C(O)NHOH、C(O)NHOR6、C(O)NHSO2R6、C(O)NR6SO2R6、
SO2NH2、SO2NHR6、SO2N(R6)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR6、C(N)N(R6)2、CNOH、CNOCH3、OH、
CN、N3、NO2, F, Cl, Br and I；
R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R4In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R7、
OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、NHR7、N(R7)2、NHC(O)R7、NR7C
(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)NH2、NHC(O)NHR7、NHC(O)N
(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N(R7)2、C(O)NHOH、C(O)NHOR7、C
(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR7、C
(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；
R5, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R5In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R8、
OR8、SR8、S(O)R8、SO2R8、NHR8、N(R8)2、C(O)R8、C(O)NH2、C(O)NHR8、C(O)N(R8)2、NHC(O)R8、NR8C
(O)R8、NHSO2R8、NHC(O)OR8、SO2NH2、SO2NHR8、SO2N(R8)2、NHC(O)NH2、NHC(O)NHR8、OH、(O)、C(O)
OH、N3、CN、NH2, F, Cl, Br and I；
R6, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R6In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R9、
OR9、SR9、S(O)R9、SO2R9、NHR9、N(R9)2、C(O)R9、C(O)NH2、C(O)NHR9、C(O)N(R9)2、NHC(O)R9、NR9C
(O)R9、NHSO2R9、NHC(O)OR9、SO2NH2、SO2NHR9、SO2N(R9)2、NHC(O)NH2、NHC(O)NHR9、OH、(O)、C(O)
OH、N3、CN、NH2、CF3、CF2CF3, F, Cl, Br and I；
R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R8, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R9, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein by R4、R5、R6、R7、R8And R9The cyclic group of expression is independently optionally independently selected by one or more from
Following substitution base substitution：R10、OR10、SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)
R10、OC(O)OR10、NH2、NHR10、N(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)
OR10、NR10C(O)OR10、NHC(O)NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、
C(O)NH2、C(O)NHR10、C(O)N(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、
SO2NH2、SO2NHR10、SO2N(R10)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、
OH、CN、N3、NO2, F, Cl, Br and I；
R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R10In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)OR11、NH2、NHR11、N(R11)2、NHC(O)
R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C(O)OR11、NHC(O)NH2、NHC(O)
NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C(O)NHR11、C(O)N(R11)2、C(O)
NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、SO2NHR11、SO2N(R11)2、C(O)H、C(O)
OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R10
In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group be each optionally independently selected by one or more from following substitution base substitution：
R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、OC(O)OR12、NH2、NHR12、N(R12)2、
NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、NR12C(O)OR12、NHC(O)NH2、NHC
(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)NH2、C(O)NHR12、C(O)N(R12)2、C
(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、SO2NHR12、SO2N(R12)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In aryl, heterocyclic radical, ring
Alkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；With
R12, it is the alkyl of independent selection when occurring every time.
In an embodiment of formula (IA), X1It is CR1And X2It is CR1.In another embodiment of formula (IA),
R1, it is hydrogen when occurring every time.In another embodiment of formula (IA), X1It is CR1, X2It is CR1, and R1Occurring every time
When be hydrogen.In another embodiment of formula (IA), Y1ForWhereinRepresent and carbonyl
Tie point,Represent the tie point with nitrogenous heteroaryl.In another embodiment of formula (IA), Y1ForWhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl；
And R2It is phenyl；Wherein R2In phenyl each by an OR4Substitution.In another embodiment of formula (IA), Y1ForWhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl；
And R2It is phenyl；Wherein R2In phenyl each by a R4Substitution.In another embodiment of formula (IA), Y1ForWhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl；
R2It is phenyl；Wherein R2In phenyl each by an OR4Substitution, and R4It is heterocyclic radical when occurring every time.At formula (IA)
Another embodiment in, Y1ForWhereinThe tie point with carbonyl is represented,Table
Show the tie point with nitrogenous heteroaryl；R2It is phenyl；Wherein R2In phenyl each by a R4Substitution, and R4Going out every time
It is now heterocyclic radical.
Further embodiment is related to compound, and it is
N- [4- ({ 1- [(2S) -2- methylbutyryls base] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } phenyl)
Azetidine -1- formamides；
3- (5- fluorine pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } benzene
Base) azetidine -1- formamides；
N- [4- ({ 1- [(2S) -2- methylbutyryls base] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2R)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (3,3,3- trifluoros propiono) piperidin-4-yl] epoxide } phenyl) azetidin
Alkane -1- formamides；
N- (4- { [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (6- picoline -3- bases)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide }
Phenyl) azetidine -1- formamides；
N- (4- { 1- [(2S) -2- methylbutyryls base] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] -1,2,3,6- tetrahydropyridine -4- bases }
Phenyl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] -1,2,3,6- tetrahydropyridine -4- bases }
Phenyl) azetidine -1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridine -3-
Base) azetidine -1- formamides；
4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) methyl benzoate；
N- (4- cyano-phenyls) -3- (pyridin-3-yl) azetidine -1- formamides；
4- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) butyl] tertiary fourth of piperidines -1- formic acid
Ester；
N- { 4- [1- (2,2- dimethylbutanoyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) -1,2,3,6- tetrahydropyridine -4- bases] phenyl }
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) -1,2,3,6- tetrahydropyridine -4- bases] phenyl }
Azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(methylsulfanyl) acetyl group] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { 1- [3- (methylsulfanyl) propiono] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- { 4- [1- (2- methylpropionyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2R)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2S)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } epoxide)
Phenyl] azetidine -1- formamides；
N- (4- { [1- (2- hydroxy-2-methyls propiono) azetidine -3- bases] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2S)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiophene -2- bases carbonyl) piperidin-4-yl] epoxide } phenyl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiene-3-yl carbonyl) piperidin-4-yl] epoxide } phenyl) azetidine-
1- formamides；
N- [4- ({ 1- [(1- Acetylpiperidin -4- bases) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ 1- [(2- methylcyclopropyl groups) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- ({ 1- [3- (morpholine -4- bases) propiono] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ 1- [3- (4- methylpiperazine-1-yls) propiono] piperidin-4-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [3- (pyrrolidin-1-yl) propiono] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
N- (4- { [1- (Cyclopropyl-acetyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (3- methylvaleryls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (4- methylvaleryls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [(1- bytyries piperidin-4-yl) epoxide] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (Ethoxyacetyl base) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (cyclopropyl carbonyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (Methoxyacetyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [(tetrahydrofuran -3- ylmethyls) carbamoyl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2- methylpropionyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- (1- benzoyl piperidine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] tertiary fourth of pyrrolidines -1- formic acid
Ester；
(3R) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1-
T-butyl formate；
(3S) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1-
T-butyl formate；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] azetidine -1- formic acid
The tert-butyl ester；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] azetidine -1- first
Tert-butyl acrylate；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] phenyl } azepine
Cyclobutane -1- formamides；
N- { 4- [1- (2- methylpropionyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } phenyl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } phenyl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] phenyl } azetidine -
1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- benzoyl pyrrole compound alkane -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { 1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- [4- (1- bytyries pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] oxygen
Base } phenyl) azetidine -1- formamides；
N- (4- { [(3R) -1- (2- methylpropionyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3R) -1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3R) -1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- benzoyl pyrrole compound alkane -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (cyclopropyl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ (3R) -1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- bytyries pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] oxygen
Base } phenyl) azetidine -1- formamides；
N- (4- { [(3S) -1- (2- methylpropionyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3S) -1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3S) -1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3S) -1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3S) -1- benzoyl pyrrole compound alkane -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- (cyclopropyl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ (3S) -1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- bytyries pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) azetidine -3- bases] phenyl }
Azetidine -1- formamides；
N- { 4- [1- (2- methylpropionyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } phenyl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } phenyl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- (1- benzoyl azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) azetidine -3- bases] phenyl } azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { 1- [(2S) -2- methylbutyryls base] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- (1- bytyry azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
4- [4- ({ [3- (2- chloropyridine -3- bases) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester；
4- [4- ({ [3- (4- chloropyridine -3- bases) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester；
N- (4- { [1- (Cyclopropyl-acetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (furans -2- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
4- [4- ({ [3- (2- fluorine pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester；
N- { 4- [(1- valeryl azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- ({ 1- [(2- methoxy ethoxies) acetyl group] azetidine -3- bases } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { [1- (Ethoxyacetyl base) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (Methoxyacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (3- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] azetidine -3- bases } epoxide) benzene
Base] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { [1- (2,3- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (4- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(2- methylcyclopropyl groups) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (4,4,4- trifluoros bytyry) azetidine -3- bases] epoxide } phenyl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (2- methylpropionyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [(1- bytyry azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [(1- propiono azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (2,2- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (3- methylbutyryls base) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (3,3,3- trifluoros propiono) azetidine -3- bases] epoxide } phenyl) nitrogen
Azetidine -1- formamides；
N- [4- ({ 1- [(1- methylcyclopropyl groups) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [1- (2- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [(1- acetyl group azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (Cyclohexylacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (cyclohexyl-carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (cyclopropyl carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiophene -2- bases carbonyl) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- (4- { [1- (cyclopentylcarbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (morpholine -4- bases acetyl group) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazole -5- bases carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
N- [4- ({ 1- [(3,5- dimethyl -1,2- oxazole -4- bases) carbonyl] azetidine -3- bases } epoxide) phenyl] -
3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiene-3-yl carbonyl) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazole-4-yls carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [1- (1,2- oxazole -5- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ 1- [(4- methylpiperazine-1-yls) acetyl group] azetidine -3- bases } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { [1- (N, N- dimethyl-β-alanyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [1- (furans -3- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ 1- [(1- methylcyclohexyls) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [1- (Cyclopentylacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazol-2-yls carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (pyrrolidin-1-yl acetyl group) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
3- (2- fluorine pyridin-3-yl)-N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2- methyl-propyls) -1H- pyrazoles -4- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- [4- (1- propyl group -1H- pyrazoles -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(3S)-tetrahydrofuran -3- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
3- (4- chloropyridine -3- bases)-N- (4- { 1- [(3S)-tetrahydrofuran -3- bases carbonyl] piperidin-4-yl } phenyl) azepine
Cyclobutane -1- formamides；
3- (2- chloropyridine -3- bases)-N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } azacyclo-
Butane -1- formamides；
4- (pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } phenyl)
Piperazine -1- formamides；
N- [4- (1- valeryls piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] piperidin-4-yl } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (4- methylvaleryls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylvaleryls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- ethoxy-cs acyl group) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2,2- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- (1- bytyries piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylbutyryls base) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (N- acetyl group-L- leucyl-s) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclohexyl-carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Cyclohexylacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (cyclopentylcarbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (furans -3- bases carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- (1- Acetylpiperidin -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- (1- propionos piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (pyrrolidin-1-yl acetyl group) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (Cyclopentylacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- (1- valeryl azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] azetidine -3- bases } phenyl) -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- { 4- [1- (4- methylvaleryls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- methylvaleryls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- ethoxy-cs acyl group) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- Dimethylpropanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- methylbutyryls base) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (N- acetyl group-L- leucyl-s) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (cyclohexyl-carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (Cyclohexylacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) azetidine -3- bases] phenyl } azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopentylcarbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [1- (furans -3- bases carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- [4- (1- acetyl group azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- (1- propiono azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopentylacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2,3- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopentyl-methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (cyclohexyl methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- methyl amyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- methyl-propyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methyl butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- ethyl-butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2,2- dimethyl propyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- methyl butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- butyl piperidine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- propylpiperdine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- cyclopropylethyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- ylmethyls) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (2,2- dimethylbutyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclopentyl-methyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (cyclohexyl methyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3,3- dimethylbutyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Cvclopropvlmethvl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2- methyl amyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -2- ylmethyls) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2- methyl-propyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3- methyl butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2- ethyl-butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2,2- dimethyl propyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2- methyl butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- ylmethyls) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2,2- dimethylbutyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- valeryls pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methylvaleryls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
N- { 4- [1- (Cyclopentylacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (furans -3- bases carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (pyrrolidin-1-yl acetyl group) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- { 4- [1- (N, N- dimethyl-β-alanyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- (4- { 1- [(4- methylpiperazine-1-yls) acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- { 4- [1- (5- oxo-L-prolyls base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- ethoxy-cs acyl group) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (4- methylvaleryls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- acetyl-pyrrolidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Cyclohexylacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- [4- (1- propionos pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { 1- [3- (morpholine -4- bases) propiono] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- Dimethylpropanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [3- (piperidin-1-yl) propiono] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (3,3- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2,2- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2- oxos propiono) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (Methoxyacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclohexyl-carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylbutyryls base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclopentylcarbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2,3- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [(3R) -1- valeryls pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [(3R) -1- (3- methylvaleryls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [1- (two rings [2.2.1] hept- 2- bases acetyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclopentylacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(2- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (morpholine -4- bases acetyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (furans -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (pyrrolidin-1-yl acetyl group) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (5- oxo-D- prolyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (N, N- dimethyl-β-alanyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (1,3- thiazol-2-yls carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (thiene-3-yl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- ({ (3R) -1- [(3 methyl thiophene -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (4,4,4- trifluoros bytyry) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- [4- ({ (3R) -1- [(4- methylpiperazine-1-yls) acetyl group] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- (4- { [(3R) -1- (5- oxo-L-prolyls base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (3- ethoxy-cs acyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (4- methylvaleryls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methylcyclohexyls) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclohexylacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (N- acetyl group-L- leucyl-s) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- propionos pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- ({ (3R) -1- [(2- methoxy ethoxies) acetyl group] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- [4- ({ (3R) -1- [3- (morpholine -4- bases) propiono] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (2,2- Dimethylpropanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ (3R) -1- [(5- methylthiophene -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (thiophene -2- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- (4- { [(3R) -1- (furans -2- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [3- (piperidin-1-yl) propiono] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Ethoxyacetyl base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (3,3- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (2,2- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (Methoxyacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (cyclohexyl-carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [(3R) -1- (3- methylbutyryls base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (cyclopentylcarbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [(3R) -1- (2,3- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- (1- benzoyl piperidine -4- bases) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides；
N- { 4- [1- (2- fluoro benzoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine；
N- { 4- [1- (2- methyl benzoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- first
Acid amides；
N- { 4- [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1-
Formamide；
N- { 4- [1- (cyclopropyl carbonyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- [4- (1- Acetylpiperidin -4- bases) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1-
Formamide；
N- { 4- [1- (cyclobutyl carbonyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
3- (pyridazine -3- bases)-N- { 4- [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- (pyridazine -3- bases)-N- { 4- [1- (3,3,3- trifluoros propiono) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine；
N- { 4- [(1- benzoyl piperidine -4- bases) methyl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine；
N- (4- { [1- (2- fluoro benzoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidin
Alkane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidin
Alkane -1- formamides；
N- (4- { [1- (2- ethylbutanoyls base) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
3- (pyridazine -3- bases)-N- (4- { [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] methyl } phenyl) azetidin
Alkane -1- formamides；
N- (4- { [1- (2- methylpropionyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- { 4- [(1- Acetylpiperidin -4- bases) methyl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- [4- ({ 1- [(2S) -2- methylbutyryls base] piperidin-4-yl } methyl) phenyl] -3- (pyridazine -3- bases) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } methyl) phenyl] -3- (pyridazine -3- bases) azacyclo-
Butane -1- formamides；With its pharmaceutically acceptable salt.
Another embodiment is related to the composition for treating following disease：Inflammation and tissue repair obstacle；Particularly
Rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fiber
Degenerative disease；The skin injury of skin disease, including psoriasis, allergic dermatitis and induced by ultraviolet irradiation；Autoimmune disease,
Including systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, mandatory rachitis, tissue and organ rejection, A Erci
The silent disease in sea, apoplexy, atherosclerosis, ISR, diabetes, glomerulonephritis, cancer, particularly wherein described cancer choosing
From breast cancer, prostate cancer, lung cancer, colon cancer, cervix cancer, oophoroma, cutaneum carcinoma, CNS cancers, carcinoma of urinary bladder, cancer of pancreas, white blood
Disease, lymthoma or Hodgkin's disease, cachexia, the inflammation related to infection and some viral infections, including acquired immunity
Deficiency symptoms (AIDS), ARDS, and ataxia-telangiectasia, the composition include tax
Formula (IA) compound of shape agent and therapeutically effective amount or its pharmaceutically acceptable salt.
Another embodiment is related to treat the method for the following disease of patient：Inflammation and tissue repair obstacle；Particularly
Rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fiber
Degenerative disease；The skin injury of skin disease, including psoriasis, allergic dermatitis and induced by ultraviolet irradiation；Autoimmune disease,
Including systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, mandatory rachitis, tissue and organ rejection, A Erci
The silent disease in sea, apoplexy, atherosclerosis, ISR, diabetes, glomerulonephritis, cancer, particularly wherein described cancer choosing
From breast cancer, prostate cancer, lung cancer, colon cancer, cervix cancer, oophoroma, cutaneum carcinoma, CNS cancers, carcinoma of urinary bladder, cancer of pancreas, white blood
Disease, lymthoma or Hodgkin's disease, cachexia, the inflammation related to infection and some viral infections, including acquired immunity
Deficiency symptoms (AIDS), ARDS, and ataxia-telangiectasia, methods described are included to institute
State formula (IA) compound or its pharmaceutically acceptable salt that patient gives therapeutically effective amount.
Another embodiment is related to treat the method for the following disease of patient：Inflammation and tissue repair obstacle；Particularly
Rheumatoid arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fiber
Degenerative disease；The skin injury of skin disease, including psoriasis, allergic dermatitis and induced by ultraviolet irradiation；Autoimmune disease,
Including systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, mandatory rachitis, tissue and organ rejection, A Erci
The silent disease in sea, apoplexy, atherosclerosis, ISR, diabetes, glomerulonephritis, cancer, particularly wherein described cancer choosing
From breast cancer, prostate cancer, lung cancer, colon cancer, cervix cancer, oophoroma, cutaneum carcinoma, CNS cancers, carcinoma of urinary bladder, cancer of pancreas, white blood
Disease, lymthoma or Hodgkin's disease, cachexia, the inflammation related to infection and some viral infections, including acquired immunity
Deficiency symptoms (AIDS), ARDS, and ataxia-telangiectasia or spleen cancer, methods described bag
Include formula (IA) compound or its pharmaceutically acceptable salt that therapeutically effective amount is given to the patient；With the one of therapeutically effective amount
Plant additional therapeutic agent or more than one additional therapeutic agent.
Detailed description of the invention
This detailed description is meant only to make others skilled in the art understand applicant's invention, its principles and its practical application,
So that others skilled in the art can in many forms change and apply the present invention, so that they can most preferably adapt to specific
The requirement of purposes.This specification and its specific embodiment are intended only to illustrate.Therefore, the invention is not restricted in this patent application
The embodiment of description can simultaneously be changed in many aspects.
Abbreviation and definition
Unless made separate stipulations herein, the scientific and technical terms for using related to the present invention should have the common skill in this area
The implication that art personnel are generally understood that.The implication and scope of these terms should be clear, but if there is any potential ambiguity, herein
The definition of offer is prior to any dictionary or external definition.In this application, unless otherwise specified, the use of "or" refer to " and/
Or ".Additionally, term " including（including）" and other forms use, for example " including（includes）" and " including
（included）", it is not restricted.On present patent application（Including claim）In word " include（comprise）”
Or " include（comprises）" or " include（comprising）" use, applicant indicate that, unless separately required in text, this
A little words are based on that they should be facultative and nonexcludability is explained is clearly understood that and uses, it is intended that explaining this patent Shen
Please, including during following claims each in these words is so explained.On herein it is any substitution base in or
Occur the variable more than once in compound of the invention or any other formula, its everywhere definition independently of it at it
The definition of its everywhere.The combination of base is replaced only just to be may be allowed to when such combination produces stable compound.The change of stabilization
Compound is the compound that it from reactant mixture can separate with useful purity.
It is to be understood that all combinations herein keep appropriate chemical valence, the monovalence portion with more than one atom
Divide and connected by their left end, divalent moiety is drawn from left to right.
As used in the specification and the appended claims, unless made opposite regulation, following term has shown implication：
Term " alkyl "（Combined alone or with another or multiple terms）Refer to usually contain 1 to about 10 carbon original
Son；Or 1 to about 8 carbon atom in another embodiment；1 to about 6 carbon atom in another embodiment；With another
1 to about 4 straight or branched saturated hydrocarbyl substitution base of carbon atom in one embodiment.The example of such substitution base includes
Methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, sec-butyl, the tert-butyl group, amyl group, isopentyl and hexyl etc..
Term " alkenyl "（Combined alone or with another or multiple terms）Refer to containing one or more double bonds and logical
Normal 2 to about 10 carbon atoms；Or 2 to about 8 carbon atoms in another embodiment；2 to big in another embodiment
About 6 carbon atoms；2 to about 4 straight or branched hydrocarbyl substituents of carbon atom in another embodiment.It is such to take
The example of Dai Ji includes vinyl, 2- acrylic, 3- acrylic, 1,4- pentadienyls, 1,4- butadienyls, 1- cyclobutenyls, 2-
Cyclobutenyl and 3- cyclobutenyls etc..
Term " alkynyl "（Combined alone or with another or multiple terms）Refer to containing one or more three keys and logical
Normal 2 to about 10 carbon atoms；Or 2 to about 8 carbon atoms in another embodiment；2 to big in another embodiment
About 6 carbon atoms；2 to about 4 straight or branched hydrocarbyl substituents of carbon atom in another embodiment.It is such to take
The example of Dai Ji is including acetenyl, 2-propynyl, 3- propinyls, 2- butynyls and 3- butynyls etc..
Term " carbocylic radical "（Combined alone or with another or multiple terms）Refer to contain 3 to 14 carboatomic ring atoms
（" annular atom " is the atom of one or more rings to form cyclic substituents of being bonded together）Saturated cyclic（That is " cycloalkanes
Base "）, fractional saturation ring-type（That is " cycloalkenyl group "）Or it is completely undersaturated（That is " aryl "）Hydrocarbyl substituent.Carbocylic radical can be
It is monocyclic（Monocyclic）Or polycyclic ring structure.
Carbocylic radical can usually contain 3 to 8 annular atoms, more generally 3 to 6 annular atoms, then more generally 5 to 6 rings
The single ring architecture of atom.The example of such monocyclic carbocyclyl residues includes cyclopropyl（Cyclopropane base）, cyclobutyl（Cyclobutane base）, ring
Amyl group（Pentamethylene base）, cyclopentenyl, cyclopentadienyl group, cyclohexyl（Cyclohexyl）, cyclohexenyl group, cyclohexadienyl and benzene
Base.Carbocylic radical can also be polycyclic（More than one ring can be contained）.The example of polycyclic carbocylic radical includes bridging, condenses and spiral shell
Ring carbon ring group.In volution carbocylic radical, an atom is that two different rings have.The example of volution carbocylic radical is spiro cyclopentane
Base.In bridging carbocylic radical base, the total non-adjacent atoms of ring shared at least two.The example of bridging carbocylic radical base includes two rings
[2.2.1] heptane base, two rings [2.2.1] hept-2-ene" base and adamantyl.In condensed ring carbocylic radical system, two or more
Ring can be fused together, so that two rings share a public key.Two-or three-condensed ring carbocylic radical example include naphthyl, tetrahydrochysene
Change naphthyl（tetralinyl）, indenyl, indanyl（Indanyl）, anthryl, phenanthryl and decahydronaphthalene naphthyl.
Term " cycloalkyl "（Combined alone or with another or multiple terms）Refer to contain 3 to 14 carboatomic ring atoms
Saturated cyclic replaces base.Cycloalkyl can usually contain 3 to 8 carboatomic ring atoms, more generally 3 to 6 single carbons of annular atom
Ring.The example of monocyclic cycloalkyl includes cyclopropyl, cyclobutyl, cyclopenta and cyclohexyl.Cycloalkyl can also be polycyclic or contain
There is more than one ring.The example of polycyclic naphthene base includes bridging, condenses and volution carbocylic radical.
Term " aryl " (being combined alone or with another or multiple terms) refers to contain 6 to 14 carboatomic ring atoms
Aromatic carbocyclyl groups.Aryl can be monocyclic or polycyclic (can contain more than one ring).In the case of polycyclic aromatic ring, only
A ring unsaturation in polycyclic system is needed, and remaining ring can be saturation, fractional saturation or undersaturated.Aryl
Example includes phenyl, naphthyl, indenyl, indanyl, and tetrahydro naphthyl.
In some cases, hydrocarbyl substituent（Such as alkyl, alkenyl, alkynyl or cycloalkyl）In carbon number by prefix
“Cx-Cy- " indicate, wherein x is the minimal amount for replacing the carbon atom in base, and y is maximum number.Thus, for example, " C1-C6- alkane
Base " refers to contain 1 to 6 alkyl substituent of carbon atom.It is further illustrated, C3-C8- cycloalkyl refers to contain 3 to 8
The saturated hydrocarbons basic ring of carboatomic ring atom.
Term " hydrogen "（Combined alone or with another or multiple terms）Refer to hydrogen-based and-H can be described as.
Term " hydroxyl "（Combined alone or with another or multiple terms）Refer to-OH.
Term " carboxyl "（Combined alone or with another or multiple terms）Refer to-C (O)-OH.
Term " amino "（Combined alone or with another or multiple terms）Refer to-NH2。
Term " halogen " or " halo "（Combined alone or with another or multiple terms）Refer to fluorine-based（It can be described
For-F）, chloro（It can be described as-Cl）, bromo（It can be described as-Br）Or iodo（It can be described as-I）.
It is described as " substituted " if instead of base, then non-hydrogen group replaces the hydrogen-based on the carbon or nitrogen of the substitution base.Cause
This, for example, the alkyl substituent of substitution is the alkyl that the non-hydrogen group of wherein at least one replaces the hydrogen-based on the alkyl substituent
Substitution base.For example, single fluoroalkyl is that, by fluorine-based substituted alkyl, fluoroalkyl is by two fluorine-based substituted alkyl.Should recognize
Know, if there is more than one substitution on substitution base, each non-hydrogen group can be with identical or different（Unless otherwise specified）.
It is described as " optionally substituted " if instead of base, the substitution base can be unsubstituted with (1), or (2) are substituted.Such as
Fruit substitution base is described as optionally by most certain amount of non-hydrogen substituent groups, and the substitution base can be unsubstituted with (1)；Or (2)
By most certain amount of non-hydrogen groups or by the maximum quantity that the may replace position substitution on most substitution bases, which is seen
It is smaller.Thus, for example, be described as optionally by the heteroaryl of most 3 non-hydrogen substituent groups if instead of base, then with being less than
What 3 any heteroaryls that may replace position were optionally at most only had with the heteroaryl may replace position non-hydrogen as many
Substituent group.For example, tetrazole radical（Its only one of which may replace position）Optionally by most non-hydrogen substituent groups.For further
For example, if ammonia nitrogen is described as optionally by most 2 non-hydrogen substituent groups, primary amino radical nitrogen is optionally by most 2
Non-hydrogen substituent group, and secondary amino nitrogen is optionally by most only 1 non-hydrogen substituent group.It is described as optionally by one if instead of base
Individual or multiple non-hydrogen substituent groups, then the substitution base can be substituted with (1)；Or (2) are by maximum on for up to substitution base
May replace the number substitution of position.Thus, for example being described as optionally by one or more non-hydrogen substituent groups if instead of base
Heteroaryl, then optionally can be taken by the non-hydrogen group of one, two or three with 3 any heteroaryls that can be substituted position
Generation.For example, tetrazole radical（It only has one and may replace position）Can optionally by most non-hydrogen substituent groups.
This patent application is used interchangeably term " substitution base " and " group（radical）”.
Prefix " halo " refers to that the substitution base of prefix connection is replaced by one or more halogen groups for independently selecting.Example
Such as, haloalkyl refers to the alkyl substituent that wherein at least one hydrogen-based is substituted by halogen group.The example of haloalkyl includes
Chloromethyl, 1- bromoethyls, methyl fluoride, difluoromethyl, trifluoromethyl and 1,1,1- trifluoroethyls.It should be appreciated that if instead of
Base is replaced by more than one halogen group, and these halogen groups can be with identical or different（Unless otherwise specified）.
Prefix " perhalogeno " refers to that the halogen group that each hydrogen-based on the substitution base of prefix connection is independently selected is substituted,
Each hydrogen-based i.e. on the substitution base is substituted by halogen group.If all halogen groups are identical, prefix generally designates halogen group.
Thus, for example, each hydrogen-based on the substitution base that term " perfluor " refers to prefix to be connected is by fluorine-based replacement.For example, term " perfluor
Alkyl " refers to the alkyl substituent of wherein each hydrogen-based of fluorine-based replacement.
Term " carbonyl "（Combined alone or with another or multiple terms）Refer to-C (O)-.
Term " amino carbonyl "（Combined alone or with another or multiple terms）Refer to-C (O)-NH2。
Term " oxo " (being combined alone or with another or multiple terms) refers to (=O).
Term " epoxide "（Combined alone or with another or multiple terms）Refer to ether substitution base and can be described as-
O-。
Term " alkyl hydroxy " (being combined alone or with another or multiple terms) refers to-alkyl-OH.
Term " alkyl amino " (being combined alone or with another or multiple terms) refers to-alkyl-NH2。
Term " alkoxy "（Combined alone or with another or multiple terms）Refer to alkyl ether substitution base, i.e.-O- alkane
Base.The example of this substitution base includes methoxyl group（-O-CH3）, ethyoxyl, positive propoxy, isopropoxy, n-butoxy, isobutyl
Epoxide, sec-butoxy and tert-butoxy.
Term " alkyl-carbonyl "（Combined alone or with another or multiple terms）It refer to-C (O)-alkyl.
Term " aminoalkylcarbonyl "（Combined alone or with another or multiple terms）Refer to-C (O)-alkyl-NH2。
Term " alkoxy carbonyl "（Combined alone or with another or multiple terms）It refer to-C (O)-O- alkyl.
Term " carbocyclylcarbonyl "（Combined alone or with another or multiple terms）It refer to-C (O)-carbocylic radical.
Similarly, term " Heterocyclylcarbonyl "（Combined alone or with another or multiple terms）It refer to-C (O)-heterocycle
Base.
Term " carbocylic radical alkyl-carbonyl "（Combined alone or with another or multiple terms）Refer to-C (O)-alkyl-carbon
Ring group.
Similarly, term " heterocyclyl alkyl carbonyl "（Combined alone or with another or multiple terms）Refer to-C (O)-
Alkyl-heterocyclyl groups.
Term " carbocylic radical Epoxide carbonyl "（Combined alone or with another or multiple terms）Refer to-C (O)-O- carbocyclic rings
Base.
Term " carbocyclylalkoxy carbonyl "（Combined alone or with another or multiple terms）Refer to-C (O)-O- alkane
Base-carbocylic radical.
Term is " thio（thio）" or " thia（thia）”（Combined alone or with another or multiple terms）Refer to sulphur
Ether replaces base, i.e., wherein bivalent sulfur atom replaces the ether substitution base of ether oxygen atom.This substitution base can be described as-S-.This
It refers to alkyl-S-alkyl to plant such as " alkyl-thio-alkyl "（Alkyl-sulfanyl（sulfanyl）- alkyl）.
Term " mercaptan（thiol）" or " sulfydryl "（Combined alone or with another or multiple terms）It refer to sulfydryl substitution
Base simultaneously can be described as-SH.
Term " (thiocarbonyl) "（Combined alone or with another or multiple terms）Refer to that wherein oxygen atom is replaced by sulphur
The carbonyl in generation.It is this substitution base can be described as-C (S)-.
Term " sulfonyl "（Combined alone or with another or multiple terms）Refer to-S (O)2-。
Term " amino-sulfonyl "（Combined alone or with another or multiple terms）Refer to-S (O)2-NH2。
Term " sulfinyl " or " sulfoxide group "（Combined alone or with another or multiple terms）Refer to-S (O)-.
Term " heterocyclic radical "（Combined alone or with another or multiple terms）Refer to contain 3 to 14 annular atoms altogether
Saturation（That is " Heterocyclylalkyl "）, fractional saturation（That is " heterocycloalkenyl "）Or it is completely undersaturated（That is " heteroaryl "）Ring knot
Structure.At least one of annular atom is hetero atom（That is oxygen, nitrogen or sulphur）, remaining annular atom is independently selected from carbon, oxygen, nitrogen and sulphur.
Heterocyclic radical can be monocyclic（Monocyclic）Or polycyclic ring structure.
Heterocyclic radical can be monocyclic, and it usually contains 3 to 7 annular atoms, more generally 3 to 6 annular atoms, then more generally 5
To 6 annular atoms.The example of monocyclic heterocycles base includes 1,2,3,6- tetrahydropyridines, thio-morpholinyl, THP trtrahydropyranyl, furans
Base, dihydrofuran base, tetrahydrofuran base, thienyl（Thio-furan base）, dihydro-thiophene base, tetrahydro-thienyl, pyrrole radicals, pyrroles
Quinoline base, pyrrolidinyl, imidazole radicals, imidazolinyl, imidazolidinyl, pyrazolyl, pyrazolinyl, pyrazolidinyl, triazolyl, tetrazolium
Base, oxazolyl, oxazole alkyl, isoxazole alkyl, isoxazolyl, thiazolyl, isothiazolyl, thiazolinyl, isothiazoline base, thiophene
Oxazolidinyl, isothiazole alkyl, thiadiazolyl group, oxadiazolyl（Including 1,2,3- oxadiazolyls, 1,2,4- oxadiazolyls, 1,2,5-
Oxadiazolyl（Furazanyl）Or 1,3,4- oxadiazolyls）, oxatriazole bases（Including 1,2,3,4- oxatriazoles base or 1,2,3,5- Evil tri-
Oxazolyl）, bis- oxazolyls（Including 1,2,3- bis- oxazolyls, 1,2,4- bis- oxazolyls, 1,3,2- bis- oxazolyls or 1,3,4- bis- oxazoles
Base), Evil thiazolyl, oxygen thia cyclopentenyl（oxathiolyl）, oxathiolane base（oxathiolanyl）, pyranose,
Dihydro pyranyl, thiapyran base, tetrahydro thiapyran base, pyridine radicals（Azine）, piperidyl, diazine（Including pyridazinyl（1,2- diazines
Base）, pyrimidine radicals（1,3- diazines）Or pyrazinyl（1,4- diazines））, piperazinyl, pyrrolidin-2-one base (pyrrolidin-
2-only), triazine radical（Including cyanuro 1,3,5,1,2,4- triazine radicals and 1,2,3- triazine radicals）, oxazinyls（Including 1,2- Evil
Piperazine base, 1,3- oxazinyls or 1,4- oxazinyls）, Evil thiazinyls（Including 1,2,3- Evil thiazinyls, 1,2,4- Evil thiazinyls, 1,2,
5- Evil thiazinyls or 1,2,6- Evil thiazinyls）, oxadiazine bases（Including 1,2,3- oxadiazines base, 1,2,4- oxadiazines base, 1,4,2-
Oxadiazine base or 1,3,5- oxadiazine bases））, morpholinyl, azepine base（azepinyl）, oxa- base（oxepinyl）, thia
Base（thiepinyl）With diaza base（diazepinyl）.
Heterocyclic radical can also be polycyclic（More than one ring can be contained）.The example of multiring heterocyclic includes bridging, thick
Close and Spirocyclic heterocyclic base.In Spirocyclic heterocyclic base, an atom is that two different rings have.In bridged heterocyclic base, ring is common
Enjoy at least two total non-adjacent atoms.In fused ring heterocycle base, two or more rings can be fused together, so that two rings
Share a public key.The example of fused ring heterocycle base includes hexahydro-furans, and simultaneously [3,4-c] pyrroles, hexahydro-furans be simultaneously [3,4-b]
Pyrroles, octahydro-pyrrolo- [3,4-b] pyridine, octahydro-pyrrolo- [3,4-c] pyridine, (3aR, 6aR) -5- methyl-octahydros-pyrroles
And [3,4-b] pyrroles, (3aR, 6aR)-octahydro-pyrrolo- [3,4-b] pyrroles, the ring [3.2.0] of 6- methyl -2,6- diazas-two
Heptane, (3aS, 6aR) -2- methyl-octahydros-pyrrolo- [3,4-c] pyrroles, decahydro-[1,5] naphthyridines, 2,3- Dihydrobenzofuranes
Base, 2,3,4,9- tetrahydrochysene -1H- pyrido [3,4-b] indyl, thieno [3,2-c] pyridine radicals, furans simultaneously [3,2-c] pyridine
Base, (2H) -one of phthalazines -1 base, isoquinolyl, (2H) -one of isoquinolin -1 base, (2H) the -one base of 5,6,7,8- tetrahydrochysenes phthalazines -1, fluorine
(2H) -one of phthalazines -1 base, (Z) -3H- benzo [d] [1,2] (5H) -one of diaza -4 base, (trifluoromethyl) phthalazines -1 (2H) -
Ketone group, pyrrolo- [1,2-d] [1,2,4] (2H) -one of triazine -1 base, 1,2,3,4- tetrahydro isoquinolyls, 2,3- dihydrobenzos [b]
[1,4] dioxa glutinous rehmannia base, (2H) the -one base of 5,6,7,8- tetrahydrochysenes phthalazines -1,5,6,7,8- tetrahydrochysenes-[1,2,4] triazol [4,3-a]
Pyrazinyl, 5,6,7,8- imidazolidines simultaneously [1,5-a] pyrazinyl, thieno [3,2-c] pyridine radicals, furans simultaneously [3,2-c] pyridine
Base, indolizine base, pyranopyrrolyl, 4H- quinolizines base, purine radicals, naphthyridines base, pyridopyridine base（Including pyrido [3,4-
B]-pyridine radicals, pyrido [3,2-b]-pyridine radicals or pyrido [4,3-b]-pyridine radicals）And pteridyl.Fused ring heterocycle base its
Its example includes benzo-fused heterocycle base, such as benzimidazolyl, benzo [d] [1,3] dioxa cyclopentenyl, indyl, different Yin
Diindyl base（Isobenzazolyl, false isoindolyl）、indoleninyl（Pseudoindolyl）, iso indazolyl（Benzopyrazoles base）, quinoline
Quinoline base（benzazinyl）（Including quinolyl（1-benzazinyl）Or isoquinolyl（2-benzazinyl））, phthalazinyl, quinoline
Quinoline base, quinazolyl, benzodiazine base（Including cinnolines base（1,2- benzodiazine bases）Or quinazolyl（1,3- benzodiazines
Base））, benzopyranyl（Including chromanyl or isochroman base）, benzoxazinyl（Including 1,3,2- benzene
Bing oxazinyls, 1,4,2- benzoxazinyls, 2,3,1- benzoxazinyls or 3,1,4- benzoxazinyls）With Ben Bing Yi oxazinyls
（Including 1,2- Ben Bing Yi oxazinyls or 1,4- Ben Bing Yi oxazinyls）.The example of Spirocyclic heterocyclic base includes 1,4- dioxa -8- nitrogen
Miscellaneous spiral shell [4.5] decyl.
Term " 3-12 circle heterocycles base " (being combined alone or with another or multiple terms) refers to contain 3 to 12 altogether
(i.e. " Heterocyclylalkyl ") of the saturation of annular atom, (i.e. " heterocycloalkenyl ") of fractional saturation or completely undersaturated (i.e. " heteroaryl
Base ") ring structure.At least one annular atom be hetero atom (i.e. oxygen, nitrogen or sulphur), remaining annular atom independently selected from carbon, oxygen,
Nitrogen and sulphur.3-12 circle heterocycles base can be monocyclic（Monocyclic）Or polycyclic ring structure.
Term " Heterocyclylalkyl " (being combined alone or with another or multiple terms) refers to saturated heterocyclyl.
Term " heteroaryl "（Combined alone or with another or multiple terms）Refer to contain 5 to 14 virtues of annular atom
Race's heterocyclic radical.Heteroaryl can be monocyclic or 2 or 3 fused rings.The example of heteroaryl substituent includes 6 yuan of ring substituents, such as pyrrole
Piperidinyl, pyrazinyl（pyrazyl）, pyrimidine radicals, pyridazinyl and 1,3,5-, 1,2,4- or 1,2,3- triazine radical；5- units ring substituents,
Such as imidazole radicals（imidazyl）, furyl, thienyl, pyrazolyl, oxazolyl, isoxazolyls, thiazolyl, 1,2,3-, 1,2,4-,
1,2,5- or 1,3,4- oxadiazolyls and isothiazolyl；6/5- units fused ring substituents, such as benzo thio-furan base, benzoisoxazole
Base, benzoxazolyl and purine radicals；With 6/6- units condensed ring, such as benzopyranyl, quinolyl, isoquinolyl, cinnolines base, quinoline azoles
Quinoline base and benzoxazinyl.
The prefix of connection multicomponent substitution base is only applicable to the first component.For example, term " alkyl-cycloalkyl " contains two
Component：Alkyl and cycloalkyl.Therefore, C1-C6C on-alkyl-cycloalkyl1-C6- prefix refers to the alkyl component of alkyl-cycloalkyl
Contain 1 to 6 carbon atom；C1-C6- prefix does not describe cycloalkyl component.To be further illustrated, on halogenated alkoxy alkyl
Prefix " halo " refer to that the only alkoxy component of alkoxyalkyl substituent is replaced by one or more halogen groups.If taken
And instead of or additionally there is halogen substitution in alkyl component, the substitution base will be changed to be described as " the alcoxyl of halogen substitution
Base alkyl " rather than " halogenated alkoxy alkyl ".Finally, if there is halogen substitution only in alkyl component, the substitution base will change
To be described as " alkoxyhaloalkyl groups ".
Term " treatment（Treat, treating and treatment）" refer to that disease and/or its subsidiary disease is mitigated or eliminated
The method of shape.
Term " prevention（Prevent, preventing and prevention）" refer to prevent disease and/or its subsidiary symptom
The method for breaking out or preventing object from falling ill." prevention " used herein also include postponing disease and/or its subsidiary paresthesia epilepsy and
Reduce the risk of falling ill of object.
Term " therapeutically effective amount " refers to the development of one or more symptom for being enough to prevent treated illness or obstacle
Or mitigate the compound dosage of one or more symptom of treated illness or obstacle to a certain extent.
Term " modulation " refers to that compound improves or reduce the function of kinases or the ability of activity.Herein with its various shape
" modulation " that formula is used is intended to include the active antagonism related to kinases, excitement, partial agonist and/or partial agonist.Kinases
Inhibitor is for example to combine partially or completely to hinder to stimulate, reduce, prevent, postpones activation, passivation, desensitization or lower signal turn
The compound led.Kinase activation agent be for example combine to stimulate, improve, open, activate, promote, chemokine, sensitization or rise signal
The compound of transduction.
Term " composition " used herein is intended to include the product of the predetermined component comprising ormal weight and by ormal weight
Predetermined component combination directly or indirectly produce any product." pharmaceutically acceptable " refers to carrier, diluent or tax
Shape agent must be compatible with other compositions of preparation and harmless to its recipient.
" object " is defined herein as including animal, such as mammal, including but not limited to, primate（For example
People）, ox, sheep, goat, horse, dog, cat, rabbit, rat, mouse etc..In preferred embodiments, this pair as if people.
Isotope enrichment or the compound of mark
Compound of the invention can with isotope marks or exist in the form of isotope enrichment, the form contains one
Or multiple atomic weight or the atom of mass number having different from naturally occurring most abundant atomic weight or mass number.Isotope
It can be radioactive or on-radiation isotope.The isotope of atom such as hydrogen, carbon, phosphorus, sulphur, fluorine, chlorine and iodine include but not
It is limited to2H, 3H, 13C, 14C, 15N, 18O, 32P, 35S, 18F, 36Cl, and125I.Its containing these and/or other atom
His compound of isotope is within the scope of the invention.
In another embodiment, the compound of isotope marks contain deuterium (2H), tritium (3H) or14C isotopes.This hair
The compound of bright isotope marks can be prepared by conventional method well known within the skill of those ordinarily skilled.Such isotope
The compound of mark can be by carrying out the step of disclosed in embodiment disclosed herein and scheme by same with what is be readily available
The reagent that the reagent of position element mark replaces non-marked is easily prepared.In some cases, compound can use isotope
The agent treatment of mark exchanges common atom with its isotope, for example can be by deuterium acid such as D2SO4/D2Hydrogen is handed in the effect of O
Change deuterium into.In addition to that mentioned above, correlation step and intermediate are disclosed in such as Lizondo, J et al.,Drugs Fut, 21
(11), 1116 (1996)；Brickner, S J et al., J Med Chem, 39(3), 673 (1996)；Mallesham,
B et al.,Org Lett, 5(7), 963 (2003)；PCT Publication WO1997010223, WO2005099353,
WO1995007271, WO2006008754；The US patent No.s 7538189；7534814；7531685；7528131；7521421；
7514068；7511013；With US patent application publication numbers 20090137457；20090131485；20090131363；
20090118238；20090111840；20090105338；20090105307；20090105147；20090093422；
20090088416；In 20090082471, these methods are incorporated herein by reference.
The compound of isotope marks of the invention can serve as standard to determine the validity in binding tests.Containing same position
The compound of element was had been used in drug research with the mechanism of action of the parent compound by evaluating nonisotopic labels and generation
Thank to approach to study internal metabolic fate (Blake et al. of compoundJ. Pharm. Sci. 64, 3, 367-391
(1975)).Such metabolism research is important in the design of safe and effective medicine, because giving the internal of patient
Reactive compound or because by the metabolin that parent compound is produced prove it is poisonous or carcinogenic (Foster et al.,
Advances in Drug Research volumes 14, the 2-36 pages, Academic press, London, 1985；Kato
Et al., J.Labelled Comp. Radiopharmaceut., 36(10):927-932 (1995)；Kushner et al.,Can. J. Physiol. Pharmacol., 77, 79-88 (1999)。
Additionally, the medicine containing non radioactive isotope, be such as referred to as the deuterated medicine of " weight medicine ", can be used for treatment with
NAMPT activity relevant disease and illness.The amount of isotope present in compound is increased above into its natural abundance to be referred to as
Enrichment.The example of the amount of enrichment include about 0.5,1,2,3,4,5,6,7,8,9,10,12,16,21,25,29,33,37,42,46,
50th, 54,58,63,67,71,75,79,84,88,92,96 to about 100 mol %.At most about 15% is being replaced with heavy isotope just
Chang Yuanzi has been realized in mammal, including rodent and dog and has been maintained several days periods to several weeks, and is observed most
Adverse reaction (Czajka D M and Finkel A J, the Ann. N.Y. Acad. Sci. 1,960 84 of lower bound degree: 770；
Thomson J F, Ann. New York Acad. Sci 1960 84: 736；Czakja D M et al., Am. J.
Physiol. 1961 201: 357).It was found that not causing toxicity using the deuterium acute replacement up to human body fluid of 15%-23%
(Blagojevic N et al. " Dosimetry ＆ Treatment Planning for Neutron Capture
Therapy ", Zamenhof R, Solares G and Harling O compile the Advanced Medical of 1994.
The 125-134 pages of Publishing, Madison Wis.；Diabetes Metab. 23: 251 (1997)).
The cold labeling of medicine can change its physicochemical property, such as pKa and lipid solubility.If isotope
Replacement have impact on and participate in the region that ligand-receptor interacts, then these influences and change can influence the pharmacodynamics of drug molecule
Reaction.Although stabilization isotope marks molecule some physical properties be different from it is unlabelled those, chemistry and biology
Property is identical, except an important exception：Because the quality of heavy isotope increases, any heavy isotope and another of being related to
The key of atom can be more stronger than the identical key between light isotope and the atom.Therefore, isotope is in metabolism or enzymatic conversion portion
The incorporation of position can slow down the reaction, may change pharmacokinetic profile or effect relative to heterotope compound.
Compound
X in formula (I) compound is selected independently1、X2、Y1、R1And R2Proper group.Reality of the present invention can be combined
Apply scheme.It is such combination be considered and within the scope of the invention.For example, it is contemplated that any one X1、X2、Y1、R1And R2Implementation
Scheme can be with any other X1、X2、Y1、R1And R2The combination of embodiment of middle restriction.
The embodiment of formula (I)
One embodiment of the invention therefore relates to compound or its pharmaceutically acceptable salt, and it can be used as NAMPT
Inhibitor, the compound has formula (I)
Formula (I)；
Wherein
X1It is N and X2It is CR1；Or
X1It is CR1And X2It is N；Or
X1It is CR1And X2It is CR1；
Y1For
WhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl；
R1, every time occur when, independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxy alkyl, alkoxy,
OH、NH2、CN、NO2, F, Cl, Br and I；
R2Independently selected from C4-C6- alkyl, C4-C6- alkenyl, C4-C6- alkynyl, aryl, 3-12 circle heterocycles base, cycloalkyl and
Cycloalkenyl group；Wherein R2In C4-C6- alkyl, C4-C6- alkenyl and C4-C6- alkynyl be each independently selected by one or more from as
Under substitution base substitution：R3、OR3、SR3、S(O)R3、SO2R3、C(O)R3、CO(O)R3、OC(O)R3、OC(O)OR3、NH2、NHR3、N
(R3)2、NHC(O)R3、NR3C(O)R3、NHS(O)2R3、NR3S(O)2R3、NHC(O)OR3、NR3C(O)OR3、NHC(O)NH2、NHC
(O)NHR3、NHC(O)N(R3)2、NR3C(O)NHR3、NR3C(O)N(R3)2、C(O)NH2、C(O)NHR3、C(O)N(R3)2、C(O)
NHOH、C(O)NHOR3、C(O)NHSO2R3、C(O)NR3SO2R3、SO2NH2、SO2NHR3、SO2N(R3)2、C(O)H、C(O)OH、C
(N)NH2、C(N)NHR3、C(N)N(R3)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R2In virtue
Base, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group are each optionally independently selected by one or more from following substitution base substitution：
R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、OC(O)OR4、NH2、NHR4、N(R4)2、NHC(O)R4、
NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)OR4、NHC(O)NH2、NHC(O)NHR4、NHC(O)N
(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、C(O)N(R4)2、C(O)NHOH、C(O)NHOR4、C
(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR4、C
(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R3, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl group and heterocyclic radical；
Wherein R3In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R5、
OR5、SR5、S(O)R5、SO2R5、C(O)R5、CO(O)R5、OC(O)R5、OC(O)OR5、NH2、NHR5、N(R5)2、NHC(O)R5、NR5C
(O)R5、NHS(O)2R5、NR5S(O)2R5、NHC(O)OR5、NR5C(O)OR5、NHC(O)NH2、NHC(O)NHR5、NHC(O)N
(R5)2、NR5C(O)NHR5、NR5C(O)N(R5)2、C(O)NH2、C(O)NHR5、C(O)N(R5)2、C(O)NHOH、C(O)NHOR5、C
(O)NHSO2R5、C(O)NR5SO2R5、SO2NH2、SO2NHR5、SO2N(R5)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR5、C
(N)N(R5)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R3In aryl, cycloalkyl, cycloalkenyl group
Following substitution base substitution is each optionally independently selected by one or more from heterocyclic radical：R6、OR6、SR6、S(O)R6、SO2R6、
C(O)R6、CO(O)R6、OC(O)R6、OC(O)OR6、NH2、NHR6、N(R6)2、NHC(O)R6、NR6C(O)R6、NHS(O)2R6、NR6S
(O)2R6、NHC(O)OR6、NR6C(O)OR6、NHC(O)NH2、NHC(O)NHR6、NHC(O)N(R6)2、NR6C(O)NHR6、NR6C(O)
N(R6)2、C(O)NH2、C(O)NHR6、C(O)N(R6)2、C(O)NHOH、C(O)NHOR6、C(O)NHSO2R6、C(O)NR6SO2R6、
SO2NH2、SO2NHR6、SO2N(R6)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR6、C(N)N(R6)2、CNOH、CNOCH3、OH、
CN、N3、NO2, F, Cl, Br and I；
R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R4In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R7、
OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、NHR7、N(R7)2、NHC(O)R7、NR7C
(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)NH2、NHC(O)NHR7、NHC(O)N
(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N(R7)2、C(O)NHOH、C(O)NHOR7、C
(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR7、C
(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；
R5, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R5In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R8、
OR8、SR8、S(O)R8、SO2R8、NHR8、N(R8)2、C(O)R8、C(O)NH2、C(O)NHR8、C(O)N(R8)2、NHC(O)R8、NR8C
(O)R8、NHSO2R8、NHC(O)OR8、SO2NH2、SO2NHR8、SO2N(R8)2、NHC(O)NH2、NHC(O)NHR8、OH、(O)、C(O)
OH、N3、CN、NH2, F, Cl, Br and I；
R6, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R6In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R9、
OR9、SR9、S(O)R9、SO2R9、NHR9、N(R9)2、C(O)R9、C(O)NH2、C(O)NHR9、C(O)N(R9)2、NHC(O)R9、NR9C
(O)R9、NHSO2R9、NHC(O)OR9、SO2NH2、SO2NHR9、SO2N(R9)2、NHC(O)NH2、NHC(O)NHR9、OH、(O)、C(O)
OH、N3、CN、NH2、CF3、CF2CF3, F, Cl, Br and I；
R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R8, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R9, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein by R4、R5、R6、R7、R8And R9The cyclic group of expression is independently optionally independently selected by one or more from
Following substitution base substitution：R10、OR10、SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)
R10、OC(O)OR10、NH2、NHR10、N(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)
OR10、NR10C(O)OR10、NHC(O)NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、
C(O)NH2、C(O)NHR10、C(O)N(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、
SO2NH2、SO2NHR10、SO2N(R10)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、
OH、CN、N3、NO2, F, Cl, Br and I；
R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R10In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)OR11、NH2、NHR11、N(R11)2、NHC(O)
R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C(O)OR11、NHC(O)NH2、NHC(O)
NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C(O)NHR11、C(O)N(R11)2、C(O)
NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、SO2NHR11、SO2N(R11)2、C(O)H、C(O)
OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R10
In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group be each optionally independently selected by one or more from following substitution base substitution：
R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、OC(O)OR12、NH2、NHR12、N(R12)2、
NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、NR12C(O)OR12、NHC(O)NH2、NHC
(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)NH2、C(O)NHR12、C(O)N(R12)2、C
(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、SO2NHR12、SO2N(R12)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In aryl, heterocyclic radical, ring
Alkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；With
R12, it is the alkyl of independent selection when occurring every time.
In an embodiment of formula (I), X1It is N and X2It is CR1.In another embodiment of formula (I), X1For
CR1And X2It is N.In another embodiment of formula (I), X1It is CR1And X2It is CR1.In another embodiment of formula (I)
In, X1It is CR1, X2It is CR1And R1When occurring every time independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyl alkane
Base, alkoxy, OH, NH2、CN、NO2, F, Cl, Br and I.In another embodiment of formula (I), X1It is CR1, X2It is CR1And
R1When occurring every time independently selected from hydrogen, alkyl, F, Cl, Br and I.In another embodiment of formula (I), X1It is CR1,
X2It is CR1And R1It is hydrogen when occurring every time.
In an embodiment of formula (I), R1, every time occur when, independently selected from hydrogen, alkyl, alkenyl, alkynyl,
Haloalkyl, hydroxy alkyl, alkoxy, OH, NH2、CN、NO2, F, Cl, Br and I.In another embodiment of formula (I),
R1, when occurring every time, independently selected from hydrogen, alkyl, F, Cl, Br and I.In another embodiment of formula (I), R1,
When occurring every time, independently selected from hydrogen, alkyl, F and Cl.In another embodiment of formula (I), R1When occurring every time
It is hydrogen.
In an embodiment of formula (I), Y1For
WhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl.In formula (I)
In another embodiment, Y1For
WhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl.In formula (I)
In another embodiment, Y1ForWhereinThe tie point with carbonyl is represented,Represent
With the tie point of nitrogenous heteroaryl.
In an embodiment of formula (I), R2Independently selected from C4-C6- alkyl, C4-C6- alkenyl, C4-C6- alkynyl, virtue
Base, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group；Wherein R2In C4-C6- alkyl, C4-C6- alkenyl and C4-C6- alkynyl is each
It is independently selected by one or more from following substitution base substitution：R3、OR3、SR3、S(O)R3、SO2R3、C(O)R3、CO(O)R3、OC
(O)R3、OC(O)OR3、NH2、NHR3、N(R3)2、NHC(O)R3、NR3C(O)R3、NHS(O)2R3、NR3S(O)2R3、NHC(O)OR3、
NR3C(O)OR3、NHC(O)NH2、NHC(O)NHR3、NHC(O)N(R3)2、NR3C(O)NHR3、NR3C(O)N(R3)2、C(O)NH2、C
(O)NHR3、C(O)N(R3)2、C(O)NHOH、C(O)NHOR3、C(O)NHSO2R3、C(O)NR3SO2R3、SO2NH2、SO2NHR3、SO2N
(R3)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR3、C(N)N(R3)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2、F、
Cl, Br and I；Wherein R2In aryl, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group each optionally by one or more independently
Replace selected from following substitution base：R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、OC(O)OR4、NH2、
NHR4、N(R4)2、NHC(O)R4、NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)OR4、NHC(O)
NH2、NHC(O)NHR4、NHC(O)N(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、C(O)N
(R4)2、C(O)NHOH、C(O)NHOR4、C(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR4、C(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.In formula (I)
In another embodiment, R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl each by one or
It is multiple to replace independently selected from following substitution base：R3, F, Cl, Br and I；Wherein R2In aryl each optionally by one or many
It is individual to replace independently selected from following substitution base：R4、OR4、CO(O)R4、C(O)NHR4, CN, F, Cl, Br and I.In the another of formula (I)
In one embodiment, R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl is each by one or many
Individual R3Substitution；Wherein R2In aryl be each optionally independently selected by one or more from following substitution base substitution：R4、OR4、
CO(O)R4、C(O)NHR4And CN.In another embodiment of formula (I), R2It is C4-C6- alkyl；Wherein R2In C4-C6- alkane
Base is each by one or more R3Substitution.In another embodiment of formula (I), R2It is aryl；Wherein R2In aryl each
It is independently selected by one or more from following substitution base substitution：R4、OR4、CO(O)R4、C(O)NHR4And CN.In the another of formula (I)
In one embodiment, R2It is aryl；Wherein R2In aryl each by C (O) NHR4Substitution.In another reality of formula (I)
In applying scheme, R2It is phenyl；Wherein R2In phenyl each by C (O) NHR4Substitution.In another embodiment of formula (I)
In, R2It is phenyl；Wherein R2In phenyl each by an OR4Substitution.In another embodiment of formula (I), R2It is benzene
Base；Wherein R2In phenyl each by a R4Substitution.
In an embodiment of formula (I), R3, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, cycloalkyl, cycloalkenyl group and heterocyclic radical；Wherein R3In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R5、OR5、SR5、S(O)R5、SO2R5、C(O)R5、CO(O)R5、OC(O)R5、OC(O)OR5、NH2、
NHR5、N(R5)2、NHC(O)R5、NR5C(O)R5、NHS(O)2R5、NR5S(O)2R5、NHC(O)OR5、NR5C(O)OR5、NHC(O)
NH2、NHC(O)NHR5、NHC(O)N(R5)2、NR5C(O)NHR5、NR5C(O)N(R5)2、C(O)NH2、C(O)NHR5、C(O)N
(R5)2、C(O)NHOH、C(O)NHOR5、C(O)NHSO2R5、C(O)NR5SO2R5、SO2NH2、SO2NHR5、SO2N(R5)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR5、C(N)N(R5)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R3
In aryl, cycloalkyl, cycloalkenyl group and heterocyclic radical be each optionally independently selected by one or more from following substitution base substitution：
R6、OR6、SR6、S(O)R6、SO2R6、C(O)R6、CO(O)R6、OC(O)R6、OC(O)OR6、NH2、NHR6、N(R6)2、NHC(O)R6、
NR6C(O)R6、NHS(O)2R6、NR6S(O)2R6、NHC(O)OR6、NR6C(O)OR6、NHC(O)NH2、NHC(O)NHR6、NHC(O)N
(R6)2、NR6C(O)NHR6、NR6C(O)N(R6)2、C(O)NH2、C(O)NHR6、C(O)N(R6)2、C(O)NHOH、C(O)NHOR6、C
(O)NHSO2R6、C(O)NR6SO2R6、SO2NH2、SO2NHR6、SO2N(R6)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR6、C
(N)N(R6)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.In another embodiment of formula (I), R3, every
It is secondary when occurring, it independently is heterocyclic radical；Wherein R3In heterocyclic radical be each optionally independently selected by one or more from it is following
Substitution base substitution：CO(O)R6, F, Cl, Br and I.In another embodiment of formula (I), R3, when occurring every time, independently
It is heterocyclic radical；Wherein R3In heterocyclic radical each optionally by one or more CO (O) R6Substitution.
In an embodiment of formula (I), R6, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R6In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R9、OR9、SR9、S(O)R9、SO2R9、NHR9、N(R9)2、C(O)R9、C(O)NH2、C(O)NHR9、
C(O)N(R9)2、NHC(O)R9、NR9C(O)R9、NHSO2R9、NHC(O)OR9、SO2NH2、SO2NHR9、SO2N(R9)2、NHC(O)
NH2、NHC(O)NHR9、OH、(O)、C(O)OH、N3、CN、NH2、CF3、CF2CF3, F, Cl, Br and I.In another reality of formula (I)
In applying scheme, R6It is alkyl when occurring every time.
In an embodiment of formula (I), R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R4In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R7、OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、
NHR7、N(R7)2、NHC(O)R7、NR7C(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)
NH2、NHC(O)NHR7、NHC(O)N(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N
(R7)2、C(O)NHOH、C(O)NHOR7、C(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR7、C(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein
By R4The cyclic group of expression is independently optionally independently selected by one or more from following substitution base substitution：R10、OR10、
SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)R10、OC(O)OR10、NH2、NHR10、N
(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)OR10、NR10C(O)OR10、NHC(O)
NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、C(O)NH2、C(O)NHR10、C(O)N
(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、SO2NH2、SO2NHR10、SO2N(R10)2、C
(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.
In another embodiment of formula (I), R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkyl
Each optionally it is independently selected by one or more from following substitution base substitution：R7, F, Cl, Br and I；Wherein by R4The ring of expression
Shape group is independently optionally independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)R10、
CO(O)R10, F, Cl, Br and I.In another embodiment of formula (I), R4It is heterocyclic radical when occurring every time.In formula (I)
In another embodiment, R4It is heterocyclic radical when occurring every time；Wherein by R4The cyclic group of expression is independently optionally by one
Or multiple replaces independently selected from following substitution base：R10、C(O)C(O)R10、C(O)R10、CO(O)R10, F, Cl, Br and I.
In an embodiment of formula (I), R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group.In another embodiment of formula (I), R7, when occurring every time, it independently is miscellaneous
Ring group.
In an embodiment of formula (I), R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R10In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R11、OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)
OR11、NH2、NHR11、N(R11)2、NHC(O)R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C
(O)OR11、NHC(O)NH2、NHC(O)NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C
(O)NHR11、C(O)N(R11)2、C(O)NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、
SO2NHR11、SO2N(R11)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、
CN、N3、NO2, F, Cl, Br and I；Wherein R10In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group each optionally by one or more
Replace independently selected from following substitution base：R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、
OC(O)OR12、NH2、NHR12、N(R12)2、NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、
NR12C(O)OR12、NHC(O)NH2、NHC(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)
NH2、C(O)NHR12、C(O)N(R12)2、C(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、
SO2NHR12、SO2N(R12)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、
N3、NO2, F, Cl, Br and I；R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl
And cycloalkenyl group；Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；R12, it is independent selection when occurring every time
Alkyl.In another embodiment of formula (I), R10, every time occur when, independently selected from alkyl, aryl, heterocyclic radical and
Cycloalkyl；Wherein R10In alkyl be each optionally independently selected by one or more from following substitution base substitution：R11、OR11、
SR11、N(R11)2、NHC(O)R11, OH, F, Cl, Br and I；Wherein R10In heterocyclic radical and cycloalkyl each optionally by one or many
It is individual to replace independently selected from following substitution base：R12、C(O)R12, F, Cl, Br and I；R11, when occurring every time, independently selected from
Alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl each optionally replaced by alkoxy；Wherein R11In heterocyclic radical and ring
Alkyl is each optionally replaced by alkyl；R12, it is the alkyl of independent selection when occurring every time.In another embodiment party of formula (I)
In case, R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10In alkyl each appoint
Choosing is independently selected by one or more from following substitution base substitution：R11、OR11、SR11、N(R11)2、NHC(O)R11, OH and F；Its
Middle R10In heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from following substitution base substitution：R12And C
(O)R12；R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In the respective optional quilt of alkyl
Alkoxy replaces；Wherein R11In heterocyclic radical and cycloalkyl each optionally replaced by alkyl；R12, it is independent when occurring every time
The alkyl of selection.
One embodiment of the invention is related to compound or its pharmaceutically acceptable salt, its suppression that can be used as NAMPT
Preparation, the compound has formula (I)
Formula (I)；
Wherein
X1It is CR1And X2It is CR1；
Y1For
WhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl；
R1, when occurring every time, independently selected from hydrogen, alkyl, F and Cl；
R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl is each by one or more R3Take
Generation；Wherein R2In aryl be each optionally independently selected by one or more from following substitution base substitution：R4、OR4、CO(O)
R4、C(O)NHR4And CN；
R3, it is heterocyclic radical when occurring every time；Wherein R3In heterocyclic radical each optionally by one or more CO (O) R6Take
Generation；
R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkyl each optionally by one or
Multiple R7Substitution；
R6, when occurring every time, it independently is alkyl；
R7, when occurring every time, it independently is heterocyclic radical；
Wherein by R4The cyclic group of expression is independently optionally independently selected by one or more from following substitution base and takes
Generation：R10、C(O)C(O)R10、C(O)R10With CO (O) R10；
R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10In alkyl it is each
Replace from following substitution base is optionally independently selected by one or more from：R11、OR11、SR11、N(R11)2、NHC(O)R11, OH and
F；Wherein R10In heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from following substitution base substitution：R12
With C (O) R12；
R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl it is each optional
Replaced by alkoxy；Wherein R11In heterocyclic radical each optionally replaced by alkyl；With
R12, it is the alkyl of independent selection when occurring every time.
Again another embodiment be related to the compound with formula (I), it include embodiment 1,2,3,4,5,6,7,8,9,
10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、
35、36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、
60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、
85、86、87、88、89、90、91、92、93、94、95、96、97、98、99、100、101、102、103、104、105、106、107、
108、109、110、111、112、113、114、115、116、117、118、119、120、121、122、123、124、125、126、
127、128、129、130、131、132、133、134、135、136、137、138、139、140、141、142、143、144、145、
146、147、148、149、150、151、152、153、154、155、156、157、158、159、160、161、162、163、164、
165、166、167、168、169、170、171、172、173、174、175、176、177、178、179、180、181、182、183、
184、185、186、187、188、189、190、191、192、193、194、195、196、197、198、199、200、201、202、
203、204、205、206、207、208、209、210、211、212、213、214、215、216、217、218、219、220、221、
222、223、224、225、226、227、228、229、230、231、232、233、234、235、236、237、238、239、240、
241、242、243、244、245、246、247、248、249、250、251、252、253、254、255、256、257、258、259、
260、261、262、263、264、265、266、267、268、269、270、271、272、273、274、275、276、277、278、
279、280、281、282、283、284、285、286、287、288、289、290、291、292、293、294、295、296、297、
298、299、300、301、302、303、304、305、306、307、308、309、310、311、312、313、314、315、316、
317、318、319、320、321、322、323、324、325、326、327、328、329、330、331、332、333、334、335,
With its pharmaceutically acceptable salt.
The embodiment of formula (II)
On the other hand, the invention provides formula (II) compound
(II)；
With its pharmaceutically acceptable salt；Wherein X1、X2、R1And R2Herein to as described in formula (I).
One embodiment of the invention is related to formula (II) compound or its pharmaceutically acceptable salt；
Wherein
X1It is N and X2It is CR1；Or
X1It is CR1And X2It is N；Or
X1It is CR1And X2It is CR1；
R1, every time occur when, independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxy alkyl, alkoxy,
OH、NH2、CN、NO2, F, Cl, Br and I；
R2Independently selected from C4-C6- alkyl, C4-C6- alkenyl, C4-C6- alkynyl, aryl, 3-12 circle heterocycles base, cycloalkyl and
Cycloalkenyl group；Wherein R2In C4-C6- alkyl, C4-C6- alkenyl and C4-C6- alkynyl be each independently selected by one or more from as
Under substitution base substitution：R3、OR3、SR3、S(O)R3、SO2R3、C(O)R3、CO(O)R3、OC(O)R3、OC(O)OR3、NH2、NHR3、N
(R3)2、NHC(O)R3、NR3C(O)R3、NHS(O)2R3、NR3S(O)2R3、NHC(O)OR3、NR3C(O)OR3、NHC(O)NH2、NHC
(O)NHR3、NHC(O)N(R3)2、NR3C(O)NHR3、NR3C(O)N(R3)2、C(O)NH2、C(O)NHR3、C(O)N(R3)2、C(O)
NHOH、C(O)NHOR3、C(O)NHSO2R3、C(O)NR3SO2R3、SO2NH2、SO2NHR3、SO2N(R3)2、C(O)H、C(O)OH、C
(N)NH2、C(N)NHR3、C(N)N(R3)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R2In virtue
Base, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group are each optionally independently selected by one or more from following substitution base substitution：
R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、OC(O)OR4、NH2、NHR4、N(R4)2、NHC(O)R4、
NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)OR4、NHC(O)NH2、NHC(O)NHR4、NHC(O)N
(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、C(O)N(R4)2、C(O)NHOH、C(O)NHOR4、C
(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR4、C
(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R3, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl group and heterocyclic radical；
Wherein R3In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R5、
OR5、SR5、S(O)R5、SO2R5、C(O)R5、CO(O)R5、OC(O)R5、OC(O)OR5、NH2、NHR5、N(R5)2、NHC(O)R5、NR5C
(O)R5、NHS(O)2R5、NR5S(O)2R5、NHC(O)OR5、NR5C(O)OR5、NHC(O)NH2、NHC(O)NHR5、NHC(O)N
(R5)2、NR5C(O)NHR5、NR5C(O)N(R5)2、C(O)NH2、C(O)NHR5、C(O)N(R5)2、C(O)NHOH、C(O)NHOR5、C
(O)NHSO2R5、C(O)NR5SO2R5、SO2NH2、SO2NHR5、SO2N(R5)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR5、C
(N)N(R5)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R3In aryl, cycloalkyl, cycloalkenyl group
Following substitution base substitution is each optionally independently selected by one or more from heterocyclic radical：R6、OR6、SR6、S(O)R6、SO2R6、
C(O)R6、CO(O)R6、OC(O)R6、OC(O)OR6、NH2、NHR6、N(R6)2、NHC(O)R6、NR6C(O)R6、NHS(O)2R6、NR6S
(O)2R6、NHC(O)OR6、NR6C(O)OR6、NHC(O)NH2、NHC(O)NHR6、NHC(O)N(R6)2、NR6C(O)NHR6、NR6C(O)
N(R6)2、C(O)NH2、C(O)NHR6、C(O)N(R6)2、C(O)NHOH、C(O)NHOR6、C(O)NHSO2R6、C(O)NR6SO2R6、
SO2NH2、SO2NHR6、SO2N(R6)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR6、C(N)N(R6)2、CNOH、CNOCH3、OH、
CN、N3、NO2, F, Cl, Br and I；
R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R4In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R7、
OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、NHR7、N(R7)2、NHC(O)R7、NR7C
(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)NH2、NHC(O)NHR7、NHC(O)N
(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N(R7)2、C(O)NHOH、C(O)NHOR7、C
(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR7、C
(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；
R5, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R5In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R8、
OR8、SR8、S(O)R8、SO2R8、NHR8、N(R8)2、C(O)R8、C(O)NH2、C(O)NHR8、C(O)N(R8)2、NHC(O)R8、NR8C
(O)R8、NHSO2R8、NHC(O)OR8、SO2NH2、SO2NHR8、SO2N(R8)2、NHC(O)NH2、NHC(O)NHR8、OH、(O)、C(O)
OH、N3、CN、NH2, F, Cl, Br and I；
R6, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R6In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R9、
OR9、SR9、S(O)R9、SO2R9、NHR9、N(R9)2、C(O)R9、C(O)NH2、C(O)NHR9、C(O)N(R9)2、NHC(O)R9、NR9C
(O)R9、NHSO2R9、NHC(O)OR9、SO2NH2、SO2NHR9、SO2N(R9)2、NHC(O)NH2、NHC(O)NHR9、OH、(O)、C(O)
OH、N3、CN、NH2、CF3、CF2CF3, F, Cl, Br and I；
R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R8, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R9, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein by R4、R5、R6、R7、R8And R9The cyclic group of expression is independently optionally independently selected by one or more from
Following substitution base substitution：R10、OR10、SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)
R10、OC(O)OR10、NH2、NHR10、N(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)
OR10、NR10C(O)OR10、NHC(O)NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、
C(O)NH2、C(O)NHR10、C(O)N(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、
SO2NH2、SO2NHR10、SO2N(R10)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、
OH、CN、N3、NO2, F, Cl, Br and I；
R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R10In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)OR11、NH2、NHR11、N(R11)2、NHC(O)
R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C(O)OR11、NHC(O)NH2、NHC(O)
NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C(O)NHR11、C(O)N(R11)2、C(O)
NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、SO2NHR11、SO2N(R11)2、C(O)H、C(O)
OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R10
In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group be each optionally independently selected by one or more from following substitution base substitution：
R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、OC(O)OR12、NH2、NHR12、N(R12)2、
NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、NR12C(O)OR12、NHC(O)NH2、NHC
(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)NH2、C(O)NHR12、C(O)N(R12)2、C
(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、SO2NHR12、SO2N(R12)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In aryl, heterocyclic radical, ring
Alkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；With
R12, it is the alkyl of independent selection when occurring every time.
In an embodiment of formula (II), X1It is N and X2It is CR1.In another embodiment of formula (II), X1
It is CR1And X2It is N.In another embodiment of formula (II), X1It is CR1And X2It is CR1.In another embodiment party of formula (II)
In case, X1It is CR1, X2It is CR1, and R1When occurring every time independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyl
Alkyl, alkoxy, OH, NH2、CN、NO2, F, Cl, Br and I.In another embodiment of formula (II), X1It is CR1, X2For
CR1, and R1When occurring every time independently selected from hydrogen, alkyl, F, Cl, Br and I.In another embodiment of formula (II),
X1It is CR1, X2It is CR1And R1It is hydrogen when occurring every time.
In an embodiment of formula (II), R1, every time occur when, independently selected from hydrogen, alkyl, alkenyl, alkynyl,
Haloalkyl, hydroxy alkyl, alkoxy, OH, NH2、CN、NO2, F, Cl, Br and I.In another embodiment of formula (II),
R1, when occurring every time, independently selected from hydrogen, alkyl, F, Cl, Br and I.In another embodiment of formula (II), R1,
When occurring every time, independently selected from hydrogen, alkyl, F and Cl.In another embodiment of formula (II), R1When occurring every time
It is hydrogen.
In an embodiment of formula (II), R2Independently selected from C4-C6- alkyl, C4-C6- alkenyl, C4-C6- alkynyl,
Aryl, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group；Wherein R2In C4-C6- alkyl, C4-C6- alkenyl and C4-C6- alkynyl is each
Replace from following substitution base is independently selected by one or more from：R3、OR3、SR3、S(O)R3、SO2R3、C(O)R3、CO(O)R3、
OC(O)R3、OC(O)OR3、NH2、NHR3、N(R3)2、NHC(O)R3、NR3C(O)R3、NHS(O)2R3、NR3S(O)2R3、NHC(O)
OR3、NR3C(O)OR3、NHC(O)NH2、NHC(O)NHR3、NHC(O)N(R3)2、NR3C(O)NHR3、NR3C(O)N(R3)2、C(O)
NH2、C(O)NHR3、C(O)N(R3)2、C(O)NHOH、C(O)NHOR3、C(O)NHSO2R3、C(O)NR3SO2R3、SO2NH2、
SO2NHR3、SO2N(R3)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR3、C(N)N(R3)2、CNOH、CNOCH3、OH、(O)、
CN、N3、NO2, F, Cl, Br and I；Wherein R2In aryl, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group each optionally by one
Or multiple replaces independently selected from following substitution base：R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、
OC(O)OR4、NH2、NHR4、N(R4)2、NHC(O)R4、NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)
OR4、NHC(O)NH2、NHC(O)NHR4、NHC(O)N(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、
C(O)N(R4)2、C(O)NHOH、C(O)NHOR4、C(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C
(O)H、C(O)OH、C(N)NH2、C(N)NHR4、C(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.
In another embodiment of formula (II), R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl is each
It is independently selected by one or more from following substitution base substitution：R3, F, Cl, Br and I；Wherein R2In the respective optional quilt of aryl
One or more replace independently selected from following substitution base：R4、OR4、CO(O)R4、C(O)NHR4, CN, F, Cl, Br and I.
In another embodiment of formula (II), R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl is each
By one or more R3Substitution；Wherein R2In aryl be each optionally independently selected by one or more from following substitution base and take
Generation：R4、OR4、CO(O)R4、C(O)NHR4And CN.In another embodiment of formula (II), R2It is C4-C6- alkyl；Wherein R2
In C4-C6- alkyl is each by one or more R3Substitution.In another embodiment of formula (II), R2It is aryl；Wherein R2
In aryl be each independently selected by one or more from following substitution base substitution：R4、OR4、CO(O)R4、C(O)NHR4With
CN.In another embodiment of formula (II), R2It is aryl；Wherein R2In aryl each by C (O) NHR4Substitution.
In another embodiment of formula (II), R2It is phenyl；Wherein R2In phenyl each by C (O) NHR4Substitution.In formula
(II) in another embodiment, R2It is phenyl；Wherein R2In phenyl each by an OR4Substitution.In the another of formula (II)
In individual embodiment, R2It is phenyl；Wherein R2In phenyl each by a R4Substitution.
In an embodiment of formula (II), R3, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, cycloalkyl, cycloalkenyl group and heterocyclic radical；Wherein R3In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R5、OR5、SR5、S(O)R5、SO2R5、C(O)R5、CO(O)R5、OC(O)R5、OC(O)OR5、NH2、
NHR5、N(R5)2、NHC(O)R5、NR5C(O)R5、NHS(O)2R5、NR5S(O)2R5、NHC(O)OR5、NR5C(O)OR5、NHC(O)
NH2、NHC(O)NHR5、NHC(O)N(R5)2、NR5C(O)NHR5、NR5C(O)N(R5)2、C(O)NH2、C(O)NHR5、C(O)N
(R5)2、C(O)NHOH、C(O)NHOR5、C(O)NHSO2R5、C(O)NR5SO2R5、SO2NH2、SO2NHR5、SO2N(R5)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR5、C(N)N(R5)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R3
In aryl, cycloalkyl, cycloalkenyl group and heterocyclic radical be each optionally independently selected by one or more from following substitution base substitution：
R6、OR6、SR6、S(O)R6、SO2R6、C(O)R6、CO(O)R6、OC(O)R6、OC(O)OR6、NH2、NHR6、N(R6)2、NHC(O)R6、
NR6C(O)R6、NHS(O)2R6、NR6S(O)2R6、NHC(O)OR6、NR6C(O)OR6、NHC(O)NH2、NHC(O)NHR6、NHC(O)N
(R6)2、NR6C(O)NHR6、NR6C(O)N(R6)2、C(O)NH2、C(O)NHR6、C(O)N(R6)2、C(O)NHOH、C(O)NHOR6、C
(O)NHSO2R6、C(O)NR6SO2R6、SO2NH2、SO2NHR6、SO2N(R6)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR6、C
(N)N(R6)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.In another embodiment of formula (II), R3,
When occurring every time, heterocyclic radical independently is；Wherein R3In heterocyclic radical be each optionally independently selected by one or more from it is as follows
Substitution base substitution：CO(O)R6, F, Cl, Br and I.In another embodiment of formula (II), R3, when occurring every time, solely
It is on the spot heterocyclic radical；Wherein R3In heterocyclic radical each optionally by one or more CO (O) R6Substitution.
In an embodiment of formula (II), R6, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R6In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R9、OR9、SR9、S(O)R9、SO2R9、NHR9、N(R9)2、C(O)R9、C(O)NH2、C(O)NHR9、
C(O)N(R9)2、NHC(O)R9、NR9C(O)R9、NHSO2R9、NHC(O)OR9、SO2NH2、SO2NHR9、SO2N(R9)2、NHC(O)
NH2、NHC(O)NHR9、OH、(O)、C(O)OH、N3、CN、NH2、CF3、CF2CF3, F, Cl, Br and I.In another reality of formula (II)
In applying scheme, R6It is alkyl when occurring every time.
In an embodiment of formula (II), R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R4In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R7、OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、
NHR7、N(R7)2、NHC(O)R7、NR7C(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)
NH2、NHC(O)NHR7、NHC(O)N(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N
(R7)2、C(O)NHOH、C(O)NHOR7、C(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR7、C(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein
By R4The cyclic group of expression is independently optionally independently selected by one or more from following substitution base substitution：R10、OR10、
SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)R10、OC(O)OR10、NH2、NHR10、N
(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)OR10、NR10C(O)OR10、NHC(O)
NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、C(O)NH2、C(O)NHR10、C(O)N
(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、SO2NH2、SO2NHR10、SO2N(R10)2、C
(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.
In another embodiment of formula (II), R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkyl
Each optionally it is independently selected by one or more from following substitution base substitution：R7, F, Cl, Br and I；Wherein by R4The ring of expression
Shape group is independently optionally independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)R10、
CO(O)R10, F, Cl, Br and I.In another embodiment of formula (II), R4It is heterocyclic radical when occurring every time.At formula (II)
Another embodiment in, R4It is heterocyclic radical when occurring every time；Wherein by R4The cyclic group of expression is independently optionally by one
Individual or multiple replaces independently selected from following substitution base：R10、C(O)C(O)R10、C(O)R10、CO(O)R10, F, Cl, Br and I.
In an embodiment of formula (II), R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group.In another embodiment of formula (II), R7, when occurring every time, it independently is
Heterocyclic radical.
In an embodiment of formula (II), R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R10In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R11、OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)
OR11、NH2、NHR11、N(R11)2、NHC(O)R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C
(O)OR11、NHC(O)NH2、NHC(O)NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C
(O)NHR11、C(O)N(R11)2、C(O)NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、
SO2NHR11、SO2N(R11)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、
CN、N3、NO2, F, Cl, Br and I；Wherein R10In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group each optionally by one or more
Replace independently selected from following substitution base：R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、
OC(O)OR12、NH2、NHR12、N(R12)2、NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、
NR12C(O)OR12、NHC(O)NH2、NHC(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)
NH2、C(O)NHR12、C(O)N(R12)2、C(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、
SO2NHR12、SO2N(R12)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、
N3、NO2, F, Cl, Br and I；R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl
And cycloalkenyl group；Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；R12, it is independent selection when occurring every time
Alkyl.In another embodiment of formula (II), R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical
And cycloalkyl；Wherein R10In alkyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、N(R11)2、NHC(O)R11, OH, F, Cl, Br and I；Wherein R10In heterocyclic radical and cycloalkyl each optionally by one
Or multiple replaces independently selected from following substitution base：R12、C(O)R12, F, Cl, Br and I；R11, when occurring every time, independently
Selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl each optionally replaced by alkoxy；Wherein R11In heterocyclic radical
Each optionally replaced by alkyl with cycloalkyl；R12, it is the alkyl of independent selection when occurring every time.Formula (II) another
In embodiment, R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10In alkyl
Each optionally it is independently selected by one or more from following substitution base substitution：R11、OR11、SR11、N(R11)2、NHC(O)R11、OH
And F；Wherein R10In heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from following substitution base substitution：
R12With C (O) R12；R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl each
Optionally replaced by alkoxy；Wherein R11In heterocyclic radical and cycloalkyl each optionally replaced by alkyl；R12, when occurring every time,
It is the alkyl of independent selection.
One embodiment of the invention is related to compound or its pharmaceutically acceptable salt, its suppression that can be used as NAMPT
Preparation, the compound has formula (II)
Formula (II)；
Wherein
X1It is CR1And X2It is CR1；
R1, when occurring every time, independently selected from hydrogen, alkyl, F and Cl；
R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl is each by one or more R3Take
Generation；Wherein R2In aryl be each optionally independently selected by one or more from following substitution base substitution：R4、OR4、CO(O)
R4、C(O)NHR4And CN；
R3, it is heterocyclic radical when occurring every time；Wherein R3In heterocyclic radical each optionally by one or more CO (O) R6Take
Generation；
R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkyl each optionally by one or
Multiple R7Substitution；
R6, when occurring every time, it independently is alkyl；
R7, when occurring every time, it independently is heterocyclic radical；
Wherein by R4The cyclic group of expression is independently optionally independently selected by one or more from following substitution base and takes
Generation：R10、C(O)C(O)R10、C(O)R10With CO (O) R10；
R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10In alkyl it is each
Replace from following substitution base is optionally independently selected by one or more from：R11、OR11、SR11、N(R11)2、NHC(O)R11, OH and
F；Wherein R10In heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from following substitution base substitution：R12
With C (O) R12；
R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl it is each optional
Replaced by alkoxy；Wherein R11In heterocyclic radical each optionally replaced by alkyl；With
R12, it is the alkyl of independent selection when occurring every time.
Another embodiment is related to the compound with formula (II), it include embodiment 1,2,3,4,5,6,7,8,9,10,
11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、
36、37、38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、
61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、
86、87、88、89、90、91、92、93、94、95、96、97、98、99、100、101、102、103、104、105、106、107、
108、109、110、111、112、113、114、115、116、117、118、119、120、121、122、123、124、125、126、
127、128、129、130、131、132、133、134、135、136、137、138、139、140、141、142、143、144、145、
146、147、148、149、150、151、152、153、154、155、156、157、158、159、160、161、163、164、165、
166、167、168、169、170、171、172、173、174、175、176、177、178、179、180、181、182、183、184、
185、186、187、188、189、190、191、192、193、194、195、196、197、198、199、200、201、202、203、
204、205、206、207、208、209、210、211、212、213、214、215、216、217、218、219、220、221、222、
223、224、225、226、227、228、229、230、231、232、233、234、235、236、237、238、239、240、241、
242、243、244、245、246、247、248、249、250、251、252、253、254、255、256、257、258、259、260、
261、262、263、264、265、266、267、268、269、270、271、272、273、274、275、276、277、278、279、
280、281、282、283、284、285、286、287、288、289、290、291、292、293、294、295、296、297、298、
299、300、301、302、303、304、305、306、307、308、309、310、311、312、313、314、315、316、317、
318th, 319,320,321,322,323,324,325,326,327,328,329,330,331,332,333,334,335, and its
Pharmaceutically acceptable salt.
The embodiment of formula (III)
On the other hand, offer formula (III) compound of the present invention
(III)；
With its pharmaceutically acceptable salt；Wherein work as R2During for aryl in formula (I), R4xAs herein for R2On substitution
Described in base.
One embodiment of the invention is related to formula (III) compound or its pharmaceutically acceptable salt；
Wherein
R4xIndependently selected from R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、OC(O)OR4、
NH2、NHR4、N(R4)2、NHC(O)R4、NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)OR4、NHC
(O)NH2、NHC(O)NHR4、NHC(O)N(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、C(O)N
(R4)2、C(O)NHOH、C(O)NHOR4、C(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR4、C(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R4In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R7、
OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、NHR7、N(R7)2、NHC(O)R7、NR7C
(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)NH2、NHC(O)NHR7、NHC(O)N
(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N(R7)2、C(O)NHOH、C(O)NHOR7、C
(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR7、C
(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；
R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein by R4And R7The cyclic group of expression is independently optionally independently selected by one or more from following substitution base
Substitution：R10、OR10、SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)R10、OC(O)OR10、
NH2、NHR10、N(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)OR10、NR10C(O)
OR10、NHC(O)NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、C(O)NH2、C(O)
NHR10、C(O)N(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、SO2NH2、SO2NHR10、
SO2N(R10)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、OH、CN、N3、NO2、F、
Cl, Br and I；
R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R10In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)OR11、NH2、NHR11、N(R11)2、NHC(O)
R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C(O)OR11、NHC(O)NH2、NHC(O)
NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C(O)NHR11、C(O)N(R11)2、C(O)
NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、SO2NHR11、SO2N(R11)2、C(O)H、C(O)
OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R10
In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group be each optionally independently selected by one or more from following substitution base substitution：
R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、OC(O)OR12、NH2、NHR12、N(R12)2、
NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、NR12C(O)OR12、NHC(O)NH2、NHC
(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)NH2、C(O)NHR12、C(O)N(R12)2、C
(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、SO2NHR12、SO2N(R12)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In aryl, heterocyclic radical, ring
Alkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；With
R12, it is the alkyl of independent selection when occurring every time.
In an embodiment of formula (III), R4xIndependently selected from R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、
CO(O)R4、OC(O)R4、OC(O)OR4、NH2、NHR4、N(R4)2、NHC(O)R4、NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、
NHC(O)OR4、NR4C(O)OR4、NHC(O)NH2、NHC(O)NHR4、NHC(O)N(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、
C(O)NH2、C(O)NHR4、C(O)N(R4)2、C(O)NHOH、C(O)NHOR4、C(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、
SO2NHR4、SO2N(R4)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR4、C(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、
NO2, F, Cl, Br and I.In another embodiment of formula (III), R4xIndependently selected from R4、OR4、CO(O)R4、C(O)
NHR4, CN, F, Cl, Br and I.In another embodiment of formula (III), R4xIndependently selected from R4、OR4、CO(O)R4、C
(O)NHR4And CN.In another embodiment of formula (III), R4xIt is C (O) NHR4.In another embodiment party of formula (III)
In case, R4xIt is OR4.In another embodiment of formula (III), R4xIt is R4。
In an embodiment of formula (III), R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R4In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R7、OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、
NHR7、N(R7)2、NHC(O)R7、NR7C(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)
NH2、NHC(O)NHR7、NHC(O)N(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N
(R7)2、C(O)NHOH、C(O)NHOR7、C(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR7、C(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein
By R4The cyclic group of expression is independently optionally independently selected by one or more from following substitution base substitution：R10、OR10、
SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)R10、OC(O)OR10、NH2、NHR10、N
(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)OR10、NR10C(O)OR10、NHC(O)
NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、C(O)NH2、C(O)NHR10、C(O)N
(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、SO2NH2、SO2NHR10、SO2N(R10)2、C
(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.
In another embodiment of formula (III), R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkane
Base is each optionally independently selected by one or more from following substitution base substitution：R7, F, Cl, Br and I；Wherein by R4Represent
Cyclic group is independently optionally independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)
R10、CO(O)R10, F, Cl, Br and I.In another embodiment of formula (III), R4, it is heterocyclic radical when occurring every time.
In another embodiment of formula (III), R4, it is heterocyclic radical when occurring every time；Wherein by R4The cyclic group independence of expression
Ground is optionally independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)R10、CO(O)R10、F、
Cl, Br and I.
In an embodiment of formula (III), R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group.In another embodiment of formula (III), R7, when occurring every time, it independently is
Heterocyclic radical.
In an embodiment of formula (III), R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R10In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R11、OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)
OR11、NH2、NHR11、N(R11)2、NHC(O)R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C
(O)OR11、NHC(O)NH2、NHC(O)NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C
(O)NHR11、C(O)N(R11)2、C(O)NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、
SO2NHR11、SO2N(R11)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、
CN、N3、NO2, F, Cl, Br and I；Wherein R10In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group each optionally by one or more
Replace independently selected from following substitution base：R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、
OC(O)OR12、NH2、NHR12、N(R12)2、NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、
NR12C(O)OR12、NHC(O)NH2、NHC(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)
NH2、C(O)NHR12、C(O)N(R12)2、C(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、
SO2NHR12、SO2N(R12)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、
N3、NO2, F, Cl, Br and I；R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl
And cycloalkenyl group；Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；R12, it is independent selection when occurring every time
Alkyl.In another embodiment of formula (III), R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical
And cycloalkyl；Wherein R10In alkyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、N(R11)2、NHC(O)R11, OH, F, Cl, Br and I；Wherein R10In heterocyclic radical and cycloalkyl each optionally by one
Or multiple replaces independently selected from following substitution base：R12、C(O)R12, F, Cl, Br and I；R11, when occurring every time, independently
Selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl each optionally replaced by alkoxy；Wherein R11In heterocyclic radical
Each optionally replaced by alkyl with cycloalkyl；R12, it is the alkyl of independent selection when occurring every time.Formula (III) another
In embodiment, R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10In alkyl
Each optionally it is independently selected by one or more from following substitution base substitution：R11、OR11、SR11、N(R11)2、NHC(O)R11、OH
And F；Wherein R10In heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from following substitution base substitution：
R12With C (O) R12；R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl each
Optionally replaced by alkoxy；Wherein R11In heterocyclic radical and cycloalkyl each optionally replaced by alkyl；R12, when occurring every time,
It is the alkyl of independent selection.
One embodiment of the invention is related to compound or its pharmaceutically acceptable salt, its suppression that can be used as NAMPT
Preparation, the compound has formula (III)
Formula (III)；
Wherein
R4x Independently selected from R4、OR4、CO(O)R4、C(O)NHR4And CN；
R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkyl each optionally by one or
Multiple R7Substitution；
R7, when occurring every time, it independently is heterocyclic radical；
Wherein by R4The cyclic group of expression is independently optionally independently selected by one or more from following substitution base and takes
Generation：R10、 C(O)C(O)R10、C(O)R10CO(O)R10；
R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10In alkyl it is each
Replace from following substitution base is optionally independently selected by one or more from：R11、OR11、SR11、N(R11)2、NHC(O)R11, OH and
F；Wherein R10In heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from following substitution base substitution：R12
With C (O) R12；
R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl it is each optional
Replaced by alkoxy；Wherein R11In heterocyclic radical each optionally replaced by alkyl；With
R12, it is the alkyl of independent selection when occurring every time.
Another embodiment is related to the compound with formula (III), it include embodiment 1,2,4,5,6,7,9,10,11,
12、13、14、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34、35、36、37、
38、39、40、41、42、43、44、45、46、47、48、49、50、51、52、53、54、55、56、57、58、59、60、61、62、
63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、86、87、
88、89、90、91、92、93、94、95、96、97、98、99、100、101、102、103、104、105、106、107、108、109、
110、111、114、115、117、118、119、120、121、122、123、124、125、126、127、128、129、130、131、
132、133、134、135、136、137、138、139、140、141、142、143、144、145、146、147、148、149、150、
151、152、153、154、155、157、158、159、163、164、165、166、167、168、169、170、171、172、173、
174、175、176、177、178、179、180、181、182、183、184、185、186、187、188、189、190、191、192、
193、194、195、196、197、198、199、200、201、202、203、204、205、206、207、208、209、210、211、
212、213、214、215、216、217、218、219、220、221、222、223、224、225、226、227、228、229、230、
231、232、233、234、235、236、237、238、239、240、241、242、243、244、245、246、247、248、249、
250、251、252、253、254、255、256、257、258、259、260、261、262、263、264、265、266、267、268、
269、270、271、272、273、274、275、276、277、278、279、280、281、282、283、284、285、286、287、
288、289、290、291、292、293、294、295、296、297、298、299、300、301、302、303、304、305、306、
307、308、309、310、311、312、313、314、315、316、317、318、319、320、321、322、323、324、325、
326th, 327,328,329,330,331,332,333,334,335, and its pharmaceutically acceptable salt.
The embodiment of formula (IA)
One embodiment of the invention therefore relates to compound or its pharmaceutically acceptable salt, and it can be used as NAMPT
Inhibitor, the compound has formula (IA)
Formula (IA)；
Wherein
X1It is N and X2It is CR1；Or
X1It is CR1And X2It is N；Or
X1It is CR1And X2It is CR1；
Y1For
WhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl；
R1, every time occur when, independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxy alkyl, alkoxy,
OH、NH2、CN、NO2, F, Cl, Br and I；
R2Independently selected from C4-C6- alkyl, C4-C6- alkenyl, C4-C6- alkynyl, aryl, 3-12 circle heterocycles base, cycloalkyl and
Cycloalkenyl group；Wherein R2In C4-C6- alkyl, C4-C6- alkenyl and C4-C6- alkynyl be each independently selected by one or more from as
Under substitution base substitution：R3、OR3、SR3、S(O)R3、SO2R3、C(O)R3、CO(O)R3、OC(O)R3、OC(O)OR3、NH2、NHR3、N
(R3)2、NHC(O)R3、NR3C(O)R3、NHS(O)2R3、NR3S(O)2R3、NHC(O)OR3、NR3C(O)OR3、NHC(O)NH2、NHC
(O)NHR3、NHC(O)N(R3)2、NR3C(O)NHR3、NR3C(O)N(R3)2、C(O)NH2、C(O)NHR3、C(O)N(R3)2、C(O)
NHOH、C(O)NHOR3、C(O)NHSO2R3、C(O)NR3SO2R3、SO2NH2、SO2NHR3、SO2N(R3)2、C(O)H、C(O)OH、C
(N)NH2、C(N)NHR3、C(N)N(R3)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R2In virtue
Base, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group are each optionally independently selected by one or more from following substitution base substitution：
R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、OC(O)OR4、NH2、NHR4、N(R4)2、NHC(O)R4、
NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)OR4、NHC(O)NH2、NHC(O)NHR4、NHC(O)N
(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、C(O)N(R4)2、C(O)NHOH、C(O)NHOR4、C
(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR4、C
(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R3, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl group and heterocyclic radical；
Wherein R3In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R5、
OR5、SR5、S(O)R5、SO2R5、C(O)R5、CO(O)R5、OC(O)R5、OC(O)OR5、NH2、NHR5、N(R5)2、NHC(O)R5、NR5C
(O)R5、NHS(O)2R5、NR5S(O)2R5、NHC(O)OR5、NR5C(O)OR5、NHC(O)NH2、NHC(O)NHR5、NHC(O)N
(R5)2、NR5C(O)NHR5、NR5C(O)N(R5)2、C(O)NH2、C(O)NHR5、C(O)N(R5)2、C(O)NHOH、C(O)NHOR5、C
(O)NHSO2R5、C(O)NR5SO2R5、SO2NH2、SO2NHR5、SO2N(R5)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR5、C
(N)N(R5)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R3In aryl, cycloalkyl, cycloalkenyl group
Following substitution base substitution is each optionally independently selected by one or more from heterocyclic radical：R6、OR6、SR6、S(O)R6、SO2R6、
C(O)R6、CO(O)R6、OC(O)R6、OC(O)OR6、NH2、NHR6、N(R6)2、NHC(O)R6、NR6C(O)R6、NHS(O)2R6、NR6S
(O)2R6、NHC(O)OR6、NR6C(O)OR6、NHC(O)NH2、NHC(O)NHR6、NHC(O)N(R6)2、NR6C(O)NHR6、NR6C(O)
N(R6)2、C(O)NH2、C(O)NHR6、C(O)N(R6)2、C(O)NHOH、C(O)NHOR6、C(O)NHSO2R6、C(O)NR6SO2R6、
SO2NH2、SO2NHR6、SO2N(R6)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR6、C(N)N(R6)2、CNOH、CNOCH3、OH、
CN、N3、NO2, F, Cl, Br and I；
R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R4In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R7、
OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、NHR7、N(R7)2、NHC(O)R7、NR7C
(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)NH2、NHC(O)NHR7、NHC(O)N
(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N(R7)2、C(O)NHOH、C(O)NHOR7、C
(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR7、C
(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；
R5, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R5In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R8、
OR8、SR8、S(O)R8、SO2R8、NHR8、N(R8)2、C(O)R8、C(O)NH2、C(O)NHR8、C(O)N(R8)2、NHC(O)R8、NR8C
(O)R8、NHSO2R8、NHC(O)OR8、SO2NH2、SO2NHR8、SO2N(R8)2、NHC(O)NH2、NHC(O)NHR8、OH、(O)、C(O)
OH、N3、CN、NH2, F, Cl, Br and I；
R6, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R6In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R9、
OR9、SR9、S(O)R9、SO2R9、NHR9、N(R9)2、C(O)R9、C(O)NH2、C(O)NHR9、C(O)N(R9)2、NHC(O)R9、NR9C
(O)R9、NHSO2R9、NHC(O)OR9、SO2NH2、SO2NHR9、SO2N(R9)2、NHC(O)NH2、NHC(O)NHR9、OH、(O)、C(O)
OH、N3、CN、NH2、CF3、CF2CF3, F, Cl, Br and I；
R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R8, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R9, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein by R4、R5、R6、R7、R8And R9The cyclic group of expression is independently optionally independently selected by one or more from
Following substitution base substitution：R10、OR10、SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)
R10、OC(O)OR10、NH2、NHR10、N(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)
OR10、NR10C(O)OR10、NHC(O)NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、
C(O)NH2、C(O)NHR10、C(O)N(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、
SO2NH2、SO2NHR10、SO2N(R10)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、
OH、CN、N3、NO2, F, Cl, Br and I；
R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R10In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)OR11、NH2、NHR11、N(R11)2、NHC(O)
R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C(O)OR11、NHC(O)NH2、NHC(O)
NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C(O)NHR11、C(O)N(R11)2、C(O)
NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、SO2NHR11、SO2N(R11)2、C(O)H、C(O)
OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R10
In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group be each optionally independently selected by one or more from following substitution base substitution：
R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、OC(O)OR12、NH2、NHR12、N(R12)2、
NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、NR12C(O)OR12、NHC(O)NH2、NHC
(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)NH2、C(O)NHR12、C(O)N(R12)2、C
(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、SO2NHR12、SO2N(R12)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In aryl, heterocyclic radical, ring
Alkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；With
R12, it is the alkyl of independent selection when occurring every time.
In an embodiment of formula (IA), X1It is N and X2It is CR1.In another embodiment of formula (IA), X1
It is CR1And X2It is N.In another embodiment of formula (IA), X1It is CR1And X2It is CR1.In another embodiment party of formula (IA)
In case, X1It is CR1, X2It is CR1And R1When occurring every time independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyl alkane
Base, alkoxy, OH, NH2、CN、NO2, F, Cl, Br and I.In another embodiment of formula (IA), X1It is CR1, X2It is CR1And
R1When occurring every time independently selected from hydrogen, alkyl, F, Cl, Br and I.In another embodiment of formula (IA), X1It is CR1,
X2It is CR1And R1It is hydrogen when occurring every time.
In an embodiment of formula (IA), R1, every time occur when, independently selected from hydrogen, alkyl, alkenyl, alkynyl,
Haloalkyl, hydroxy alkyl, alkoxy, OH, NH2、CN、NO2, F, Cl, Br and I.In another embodiment of formula (IA),
R1, when occurring every time, independently selected from hydrogen, alkyl, F, Cl, Br and I.In another embodiment of formula (IA), R1,
When occurring every time, independently selected from hydrogen, alkyl, F and Cl.In another embodiment of formula (IA), R1When occurring every time
It is hydrogen.
In an embodiment of formula (IA), Y1For
WhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl.At formula (IA)
Another embodiment in, Y1For
WhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl.At formula (IA)
Another embodiment in, Y1ForWhereinThe tie point with carbonyl is represented,Table
Show the tie point with nitrogenous heteroaryl.
In an embodiment of formula (IA), R2Independently selected from C4-C6- alkyl, C4-C6- alkenyl, C4-C6- alkynyl,
Aryl, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group；Wherein R2In C4-C6- alkyl, C4-C6- alkenyl and C4-C6- alkynyl is each
Replace from following substitution base is independently selected by one or more from：R3、OR3、SR3、S(O)R3、SO2R3、C(O)R3、CO(O)R3、
OC(O)R3、OC(O)OR3、NH2、NHR3、N(R3)2、NHC(O)R3、NR3C(O)R3、NHS(O)2R3、NR3S(O)2R3、NHC(O)
OR3、NR3C(O)OR3、NHC(O)NH2、NHC(O)NHR3、NHC(O)N(R3)2、NR3C(O)NHR3、NR3C(O)N(R3)2、C(O)
NH2、C(O)NHR3、C(O)N(R3)2、C(O)NHOH、C(O)NHOR3、C(O)NHSO2R3、C(O)NR3SO2R3、SO2NH2、
SO2NHR3、SO2N(R3)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR3、C(N)N(R3)2、CNOH、CNOCH3、OH、(O)、
CN、N3、NO2, F, Cl, Br and I；Wherein R2In aryl, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group each optionally by one
Or multiple replaces independently selected from following substitution base：R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、
OC(O)OR4、NH2、NHR4、N(R4)2、NHC(O)R4、NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)
OR4、NHC(O)NH2、NHC(O)NHR4、NHC(O)N(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、
C(O)N(R4)2、C(O)NHOH、C(O)NHOR4、C(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C
(O)H、C(O)OH、C(N)NH2、C(N)NHR4、C(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.
In another embodiment of formula (IA), R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl is each
It is independently selected by one or more from following substitution base substitution：R3, F, Cl, Br and I；Wherein R2In the respective optional quilt of aryl
One or more replace independently selected from following substitution base：R4、OR4、CO(O)R4、C(O)NHR4, CN, F, Cl, Br and I.
In another embodiment of formula (IA), R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl is each
By one or more R3Substitution；Wherein R2In aryl be each optionally independently selected by one or more from following substitution base and take
Generation：R4、OR4、CO(O)R4、C(O)NHR4And CN.In another embodiment of formula (IA), R2It is C4-C6- alkyl；Wherein R2
In C4-C6- alkyl is each by one or more R3Substitution.In another embodiment of formula (IA), R2It is aryl；Wherein R2
In aryl be each independently selected by one or more from following substitution base substitution：R4、OR4、CO(O)R4、C(O)NHR4With
CN.In another embodiment of formula (IA), R2It is aryl；Wherein R2In aryl each by C (O) NHR4Substitution.
In another embodiment of formula (IA), R2It is phenyl；Wherein R2In phenyl each by C (O) NHR4Substitution.In formula
(IA) in another embodiment, R2It is phenyl；Wherein R2In phenyl each by an OR4Substitution.In the another of formula (IA)
In individual embodiment, R2It is phenyl；Wherein R2In phenyl each by a R4Substitution.
In an embodiment of formula (IA), R3, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, cycloalkyl, cycloalkenyl group and heterocyclic radical；Wherein R3In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R5、OR5、SR5、S(O)R5、SO2R5、C(O)R5、CO(O)R5、OC(O)R5、OC(O)OR5、NH2、
NHR5、N(R5)2、NHC(O)R5、NR5C(O)R5、NHS(O)2R5、NR5S(O)2R5、NHC(O)OR5、NR5C(O)OR5、NHC(O)
NH2、NHC(O)NHR5、NHC(O)N(R5)2、NR5C(O)NHR5、NR5C(O)N(R5)2、C(O)NH2、C(O)NHR5、C(O)N
(R5)2、C(O)NHOH、C(O)NHOR5、C(O)NHSO2R5、C(O)NR5SO2R5、SO2NH2、SO2NHR5、SO2N(R5)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR5、C(N)N(R5)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R3
In aryl, cycloalkyl, cycloalkenyl group and heterocyclic radical be each optionally independently selected by one or more from following substitution base substitution：
R6、OR6、SR6、S(O)R6、SO2R6、C(O)R6、CO(O)R6、OC(O)R6、OC(O)OR6、NH2、NHR6、N(R6)2、NHC(O)R6、
NR6C(O)R6、NHS(O)2R6、NR6S(O)2R6、NHC(O)OR6、NR6C(O)OR6、NHC(O)NH2、NHC(O)NHR6、NHC(O)N
(R6)2、NR6C(O)NHR6、NR6C(O)N(R6)2、C(O)NH2、C(O)NHR6、C(O)N(R6)2、C(O)NHOH、C(O)NHOR6、C
(O)NHSO2R6、C(O)NR6SO2R6、SO2NH2、SO2NHR6、SO2N(R6)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR6、C
(N)N(R6)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.In another embodiment of formula (IA), R3,
When occurring every time, heterocyclic radical independently is；Wherein R3In heterocyclic radical be each optionally independently selected by one or more from it is as follows
Substitution base substitution：CO(O)R6, F, Cl, Br and I.In another embodiment of formula (IA), R3, when occurring every time, solely
It is on the spot heterocyclic radical；Wherein R3In heterocyclic radical each optionally by one or more CO (O) R6Substitution.
In an embodiment of formula (IA), R6, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R6In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R9、OR9、SR9、S(O)R9、SO2R9、NHR9、N(R9)2、C(O)R9、C(O)NH2、C(O)NHR9、
C(O)N(R9)2、NHC(O)R9、NR9C(O)R9、NHSO2R9、NHC(O)OR9、SO2NH2、SO2NHR9、SO2N(R9)2、NHC(O)
NH2、NHC(O)NHR9、OH、(O)、C(O)OH、N3、CN、NH2、CF3、CF2CF3, F, Cl, Br and I.In another reality of formula (IA)
In applying scheme, R6It is alkyl when occurring every time.
In an embodiment of formula (IA), R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R4In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R7、OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、
NHR7、N(R7)2、NHC(O)R7、NR7C(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)
NH2、NHC(O)NHR7、NHC(O)N(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N
(R7)2、C(O)NHOH、C(O)NHOR7、C(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR7、C(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein
By R4The cyclic group of expression is independently optionally independently selected by one or more from following substitution base substitution：R10、OR10、
SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)R10、OC(O)OR10、NH2、NHR10、N
(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)OR10、NR10C(O)OR10、NHC(O)
NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、C(O)NH2、C(O)NHR10、C(O)N
(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、SO2NH2、SO2NHR10、SO2N(R10)2、C
(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.
In another embodiment of formula (IA), R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkyl
Each optionally it is independently selected by one or more from following substitution base substitution：R7, F, Cl, Br and I；Wherein by R4The ring of expression
Shape group is independently optionally independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)R10、
CO(O)R10, F, Cl, Br and I.In another embodiment of formula (IA), R4It is heterocyclic radical when occurring every time.At formula (IA)
Another embodiment in, R4It is heterocyclic radical when occurring every time；Wherein by R4The cyclic group of expression is independently optionally by one
Individual or multiple replaces independently selected from following substitution base：R10、C(O)C(O)R10、C(O)R10、CO(O)R10, F, Cl, Br and I.
In an embodiment of formula (IA), R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group.In another embodiment of formula (IA), R7, when occurring every time, it independently is
Heterocyclic radical.In another embodiment of formula (IA), R7It is heterocyclic radical when occurring every time；Wherein by R7The cyclic group of expression
Group is independently optionally independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)R10、CO
(O)R10, F, Cl, Br and I.
In an embodiment of formula (IA), R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R10In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R11、OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)
OR11、NH2、NHR11、N(R11)2、NHC(O)R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C
(O)OR11、NHC(O)NH2、NHC(O)NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C
(O)NHR11、C(O)N(R11)2、C(O)NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、
SO2NHR11、SO2N(R11)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、
CN、N3、NO2, F, Cl, Br and I；Wherein R10In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group each optionally by one or more
Replace independently selected from following substitution base：R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、
OC(O)OR12、NH2、NHR12、N(R12)2、NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、
NR12C(O)OR12、NHC(O)NH2、NHC(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)
NH2、C(O)NHR12、C(O)N(R12)2、C(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、
SO2NHR12、SO2N(R12)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、
N3、NO2, F, Cl, Br and I；R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl
And cycloalkenyl group；Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；R12, it is independent selection when occurring every time
Alkyl.In another embodiment of formula (IA), R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical
And cycloalkyl；Wherein R10In alkyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、N(R11)2、NHC(O)R11, OH, F, Cl, Br and I；Wherein R10In aryl, heterocyclic radical and cycloalkyl it is each optional
It is independently selected by one or more from following substitution base substitution：R12、C(O)R12, F, Cl, Br and I；R11, when occurring every time,
Independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl each optionally replaced by alkoxy；Wherein R11In
Heterocyclic radical and cycloalkyl are each optionally replaced by alkyl；R12, it is the alkyl of independent selection when occurring every time.In formula (IA)
In another embodiment, R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10In
Alkyl be each optionally independently selected by one or more from following substitution base substitution：R11、OR11、SR11、N(R11)2、NHC
(O)R11, OH and F；Wherein R10In aryl, heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from it is as follows
Substitution base substitution：R12、C(O)R12And F；R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein
R11In alkyl each optionally replaced by alkoxy；Wherein R11In heterocyclic radical and cycloalkyl each optionally replaced by alkyl；
R12, it is the alkyl of independent selection when occurring every time.
One embodiment of the invention is related to compound or its pharmaceutically acceptable salt, its suppression that can be used as NAMPT
Preparation, the compound has formula (IA)
Formula (IA)；
Wherein
X1It is CR1And X2It is CR1；
Y1For
WhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl；
R1, when occurring every time, independently selected from hydrogen, alkyl, F and Cl；
R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl is each by one or more R3Take
Generation；Wherein R2In aryl be each optionally independently selected by one or more from following substitution base substitution：R4、OR4、CO(O)
R4、C(O)NHR4And CN；
R3It is heterocyclic radical when occurring every time；Wherein R3In heterocyclic radical each optionally by one or more CO (O) R6Take
Generation；
R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkyl each optionally by one or
Multiple R7Substitution；
R6, when occurring every time, it independently is alkyl；
R7, when occurring every time, it independently is heterocyclic radical；
Wherein by R4And R7The cyclic group of expression is independently optionally independently selected by one or more from following substitution base
Substitution：R10、C(O)C(O)R10、C(O)R10With CO (O) R10；
R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10In alkyl it is each
Replace from following substitution base is optionally independently selected by one or more from：R11、OR11、SR11、N(R11)2、NHC(O)R11, OH and
F；Wherein R10In aryl, heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from following substitution base and take
Generation：R12、C(O)R12And F；
R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl it is each optional
Replaced by alkoxy；Wherein R11In heterocyclic radical each optionally replaced by alkyl；With
R12, it is the alkyl of independent selection when occurring every time.
Another embodiment is related to the compound with formula (IA), and it includes
N- [4- ({ 1- [(2S) -2- methylbutyryls base] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } phenyl)
Azetidine -1- formamides；
3- (5- fluorine pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } benzene
Base) azetidine -1- formamides；
N- [4- ({ 1- [(2S) -2- methylbutyryls base] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2R)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (3,3,3- trifluoros propiono) piperidin-4-yl] epoxide } phenyl) azetidin
Alkane -1- formamides；
N- (4- { [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (6- picoline -3- bases)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide }
Phenyl) azetidine -1- formamides；
N- (4- { 1- [(2S) -2- methylbutyryls base] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] -1,2,3,6- tetrahydropyridine -4- bases }
Phenyl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] -1,2,3,6- tetrahydropyridine -4- bases }
Phenyl) azetidine -1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridine -3-
Base) azetidine -1- formamides；
4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) methyl benzoate；
N- (4- cyano-phenyls) -3- (pyridin-3-yl) azetidine -1- formamides；
4- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) butyl] tertiary fourth of piperidines -1- formic acid
Ester；
N- { 4- [1- (2,2- dimethylbutanoyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) -1,2,3,6- tetrahydropyridine -4- bases] phenyl }
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) -1,2,3,6- tetrahydropyridine -4- bases] phenyl }
Azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(methylsulfanyl) acetyl group] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { 1- [3- (methylsulfanyl) propiono] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- { 4- [1- (2- methylpropionyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2R)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2S)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } epoxide)
Phenyl] azetidine -1- formamides；
N- (4- { [1- (2- hydroxy-2-methyls propiono) azetidine -3- bases] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2S)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiophene -2- bases carbonyl) piperidin-4-yl] epoxide } phenyl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiene-3-yl carbonyl) piperidin-4-yl] epoxide } phenyl) azetidine-
1- formamides；
N- [4- ({ 1- [(1- Acetylpiperidin -4- bases) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ 1- [(2- methylcyclopropyl groups) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- ({ 1- [3- (morpholine -4- bases) propiono] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ 1- [3- (4- methylpiperazine-1-yls) propiono] piperidin-4-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [3- (pyrrolidin-1-yl) propiono] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
N- (4- { [1- (Cyclopropyl-acetyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (3- methylvaleryls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (4- methylvaleryls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [(1- bytyries piperidin-4-yl) epoxide] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (Ethoxyacetyl base) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (cyclopropyl carbonyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (Methoxyacetyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [(tetrahydrofuran -3- ylmethyls) carbamoyl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2- methylpropionyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- (1- benzoyl piperidine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] tertiary fourth of pyrrolidines -1- formic acid
Ester；
(3R) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1-
T-butyl formate；
(3S) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1-
T-butyl formate；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] azetidine -1- formic acid
The tert-butyl ester；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] azetidine -1- first
Tert-butyl acrylate；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] phenyl } azepine
Cyclobutane -1- formamides；
N- { 4- [1- (2- methylpropionyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } phenyl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } phenyl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] phenyl } azetidine -
1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- benzoyl pyrrole compound alkane -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { 1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- [4- (1- bytyries pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] oxygen
Base } phenyl) azetidine -1- formamides；
N- (4- { [(3R) -1- (2- methylpropionyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3R) -1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3R) -1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- benzoyl pyrrole compound alkane -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (cyclopropyl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ (3R) -1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- bytyries pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] oxygen
Base } phenyl) azetidine -1- formamides；
N- (4- { [(3S) -1- (2- methylpropionyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3S) -1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3S) -1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3S) -1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3S) -1- benzoyl pyrrole compound alkane -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- (cyclopropyl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ (3S) -1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- bytyries pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) azetidine -3- bases] phenyl }
Azetidine -1- formamides；
N- { 4- [1- (2- methylpropionyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } phenyl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } phenyl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- (1- benzoyl azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) azetidine -3- bases] phenyl } azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { 1- [(2S) -2- methylbutyryls base] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- (1- bytyry azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
4- [4- ({ [3- (2- chloropyridine -3- bases) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester；
4- [4- ({ [3- (4- chloropyridine -3- bases) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester；
N- (4- { [1- (Cyclopropyl-acetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (furans -2- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
4- [4- ({ [3- (2- fluorine pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester；
N- { 4- [(1- valeryl azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- ({ 1- [(2- methoxy ethoxies) acetyl group] azetidine -3- bases } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { [1- (Ethoxyacetyl base) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (Methoxyacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (3- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] azetidine -3- bases } epoxide) benzene
Base] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { [1- (2,3- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (4- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(2- methylcyclopropyl groups) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (4,4,4- trifluoros bytyry) azetidine -3- bases] epoxide } phenyl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (2- methylpropionyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [(1- bytyry azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [(1- propiono azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (2,2- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (3- methylbutyryls base) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (3,3,3- trifluoros propiono) azetidine -3- bases] epoxide } phenyl) nitrogen
Azetidine -1- formamides；
N- [4- ({ 1- [(1- methylcyclopropyl groups) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [1- (2- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [(1- acetyl group azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (Cyclohexylacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (cyclohexyl-carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (cyclopropyl carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiophene -2- bases carbonyl) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- (4- { [1- (cyclopentylcarbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (morpholine -4- bases acetyl group) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazole -5- bases carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
N- [4- ({ 1- [(3,5- dimethyl -1,2- oxazole -4- bases) carbonyl] azetidine -3- bases } epoxide) phenyl] -
3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiene-3-yl carbonyl) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazole-4-yls carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [1- (1,2- oxazole -5- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ 1- [(4- methylpiperazine-1-yls) acetyl group] azetidine -3- bases } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { [1- (N, N- dimethyl-β-alanyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [1- (furans -3- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ 1- [(1- methylcyclohexyls) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [1- (Cyclopentylacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazol-2-yls carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (pyrrolidin-1-yl acetyl group) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
3- (2- fluorine pyridin-3-yl)-N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2- methyl-propyls) -1H- pyrazoles -4- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- [4- (1- propyl group -1H- pyrazoles -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(3S)-tetrahydrofuran -3- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
3- (4- chloropyridine -3- bases)-N- (4- { 1- [(3S)-tetrahydrofuran -3- bases carbonyl] piperidin-4-yl } phenyl) azepine
Cyclobutane -1- formamides；
3- (2- chloropyridine -3- bases)-N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } azacyclo-
Butane -1- formamides；
4- (pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } phenyl)
Piperazine -1- formamides；
N- [4- (1- valeryls piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] piperidin-4-yl } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (4- methylvaleryls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylvaleryls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- ethoxy-cs acyl group) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2,2- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- (1- bytyries piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylbutyryls base) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (N- acetyl group-L- leucyl-s) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclohexyl-carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Cyclohexylacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (cyclopentylcarbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (furans -3- bases carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- (1- Acetylpiperidin -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- (1- propionos piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (pyrrolidin-1-yl acetyl group) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (Cyclopentylacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- (1- valeryl azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] azetidine -3- bases } phenyl) -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- { 4- [1- (4- methylvaleryls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- methylvaleryls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- ethoxy-cs acyl group) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- Dimethylpropanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- methylbutyryls base) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (N- acetyl group-L- leucyl-s) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (cyclohexyl-carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (Cyclohexylacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) azetidine -3- bases] phenyl } azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopentylcarbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [1- (furans -3- bases carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- [4- (1- acetyl group azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- (1- propiono azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopentylacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2,3- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopentyl-methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (cyclohexyl methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- methyl amyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- methyl-propyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methyl butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- ethyl-butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2,2- dimethyl propyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- methyl butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- butyl piperidine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- propylpiperdine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- cyclopropylethyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- ylmethyls) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (2,2- dimethylbutyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclopentyl-methyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (cyclohexyl methyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3,3- dimethylbutyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Cvclopropvlmethvl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2- methyl amyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -2- ylmethyls) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2- methyl-propyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3- methyl butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2- ethyl-butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2,2- dimethyl propyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2- methyl butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- ylmethyls) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2,2- dimethylbutyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- valeryls pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methylvaleryls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
N- { 4- [1- (Cyclopentylacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (furans -3- bases carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (pyrrolidin-1-yl acetyl group) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- { 4- [1- (N, N- dimethyl-β-alanyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- (4- { 1- [(4- methylpiperazine-1-yls) acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- { 4- [1- (5- oxo-L-prolyls base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- ethoxy-cs acyl group) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (4- methylvaleryls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- acetyl-pyrrolidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Cyclohexylacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- [4- (1- propionos pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { 1- [3- (morpholine -4- bases) propiono] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- Dimethylpropanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [3- (piperidin-1-yl) propiono] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (3,3- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2,2- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2- oxos propiono) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (Methoxyacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclohexyl-carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylbutyryls base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclopentylcarbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2,3- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [(3R) -1- valeryls pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [(3R) -1- (3- methylvaleryls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [1- (two rings [2.2.1] hept- 2- bases acetyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclopentylacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(2- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (morpholine -4- bases acetyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (furans -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (pyrrolidin-1-yl acetyl group) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (5- oxo-D- prolyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (N, N- dimethyl-β-alanyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (1,3- thiazol-2-yls carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (thiene-3-yl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- ({ (3R) -1- [(3 methyl thiophene -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (4,4,4- trifluoros bytyry) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- [4- ({ (3R) -1- [(4- methylpiperazine-1-yls) acetyl group] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- (4- { [(3R) -1- (5- oxo-L-prolyls base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (3- ethoxy-cs acyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (4- methylvaleryls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methylcyclohexyls) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclohexylacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (N- acetyl group-L- leucyl-s) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- propionos pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- ({ (3R) -1- [(2- methoxy ethoxies) acetyl group] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- [4- ({ (3R) -1- [3- (morpholine -4- bases) propiono] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (2,2- Dimethylpropanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ (3R) -1- [(5- methylthiophene -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (thiophene -2- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- (4- { [(3R) -1- (furans -2- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [3- (piperidin-1-yl) propiono] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Ethoxyacetyl base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (3,3- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (2,2- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (Methoxyacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (cyclohexyl-carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [(3R) -1- (3- methylbutyryls base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (cyclopentylcarbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [(3R) -1- (2,3- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- (1- benzoyl piperidine -4- bases) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides；
N- { 4- [1- (2- fluoro benzoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine；
N- { 4- [1- (2- methyl benzoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- first
Acid amides；
N- { 4- [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1-
Formamide；
N- { 4- [1- (cyclopropyl carbonyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- [4- (1- Acetylpiperidin -4- bases) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1-
Formamide；
N- { 4- [1- (cyclobutyl carbonyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
3- (pyridazine -3- bases)-N- { 4- [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- (pyridazine -3- bases)-N- { 4- [1- (3,3,3- trifluoros propiono) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine；
N- { 4- [(1- benzoyl piperidine -4- bases) methyl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine；
N- (4- { [1- (2- fluoro benzoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidin
Alkane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidin
Alkane -1- formamides；
N- (4- { [1- (2- ethylbutanoyls base) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
3- (pyridazine -3- bases)-N- (4- { [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] methyl } phenyl) azetidin
Alkane -1- formamides；
N- (4- { [1- (2- methylpropionyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- { 4- [(1- Acetylpiperidin -4- bases) methyl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- [4- ({ 1- [(2S) -2- methylbutyryls base] piperidin-4-yl } methyl) phenyl] -3- (pyridazine -3- bases) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } methyl) phenyl] -3- (pyridazine -3- bases) azacyclo-
Butane -1- formamides；With its pharmaceutically acceptable salt.
The embodiment of formula (IIA)
On the other hand, offer formula (IIA) compound of the present invention
(IIA)；
With its pharmaceutically acceptable salt；Wherein X1、X2、R1And R2Herein to as described in formula (IA).
One embodiment of the invention is related to formula (IIA) compound or its pharmaceutically acceptable salt；
Wherein
X1It is N and X2It is CR1；Or
X1It is CR1And X2It is N；Or
X1It is CR1And X2It is CR1；
R1, every time occur when, independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxy alkyl, alkoxy,
OH、NH2、CN、NO2, F, Cl, Br and I；
R2Independently selected from C4-C6- alkyl, C4-C6- alkenyl, C4-C6- alkynyl, aryl, 3-12 circle heterocycles base, cycloalkyl and
Cycloalkenyl group；Wherein R2In C4-C6- alkyl, C4-C6- alkenyl and C4-C6- alkynyl be each independently selected by one or more from as
Under substitution base substitution：R3、OR3、SR3、S(O)R3、SO2R3、C(O)R3、CO(O)R3、OC(O)R3、OC(O)OR3、NH2、NHR3、N
(R3)2、NHC(O)R3、NR3C(O)R3、NHS(O)2R3、NR3S(O)2R3、NHC(O)OR3、NR3C(O)OR3、NHC(O)NH2、NHC
(O)NHR3、NHC(O)N(R3)2、NR3C(O)NHR3、NR3C(O)N(R3)2、C(O)NH2、C(O)NHR3、C(O)N(R3)2、C(O)
NHOH、C(O)NHOR3、C(O)NHSO2R3、C(O)NR3SO2R3、SO2NH2、SO2NHR3、SO2N(R3)2、C(O)H、C(O)OH、C
(N)NH2、C(N)NHR3、C(N)N(R3)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R2In virtue
Base, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group are each optionally independently selected by one or more from following substitution base substitution：
R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、OC(O)OR4、NH2、NHR4、N(R4)2、NHC(O)R4、
NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)OR4、NHC(O)NH2、NHC(O)NHR4、NHC(O)N
(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、C(O)N(R4)2、C(O)NHOH、C(O)NHOR4、C
(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR4、C
(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R3, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl group and heterocyclic radical；
Wherein R3In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R5、
OR5、SR5、S(O)R5、SO2R5、C(O)R5、CO(O)R5、OC(O)R5、OC(O)OR5、NH2、NHR5、N(R5)2、NHC(O)R5、NR5C
(O)R5、NHS(O)2R5、NR5S(O)2R5、NHC(O)OR5、NR5C(O)OR5、NHC(O)NH2、NHC(O)NHR5、NHC(O)N
(R5)2、NR5C(O)NHR5、NR5C(O)N(R5)2、C(O)NH2、C(O)NHR5、C(O)N(R5)2、C(O)NHOH、C(O)NHOR5、C
(O)NHSO2R5、C(O)NR5SO2R5、SO2NH2、SO2NHR5、SO2N(R5)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR5、C
(N)N(R5)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R3In aryl, cycloalkyl, cycloalkenyl group
Following substitution base substitution is each optionally independently selected by one or more from heterocyclic radical：R6、OR6、SR6、S(O)R6、SO2R6、
C(O)R6、CO(O)R6、OC(O)R6、OC(O)OR6、NH2、NHR6、N(R6)2、NHC(O)R6、NR6C(O)R6、NHS(O)2R6、NR6S
(O)2R6、NHC(O)OR6、NR6C(O)OR6、NHC(O)NH2、NHC(O)NHR6、NHC(O)N(R6)2、NR6C(O)NHR6、NR6C(O)
N(R6)2、C(O)NH2、C(O)NHR6、C(O)N(R6)2、C(O)NHOH、C(O)NHOR6、C(O)NHSO2R6、C(O)NR6SO2R6、
SO2NH2、SO2NHR6、SO2N(R6)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR6、C(N)N(R6)2、CNOH、CNOCH3、OH、
CN、N3、NO2, F, Cl, Br and I；
R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R4In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R7、
OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、NHR7、N(R7)2、NHC(O)R7、NR7C
(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)NH2、NHC(O)NHR7、NHC(O)N
(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N(R7)2、C(O)NHOH、C(O)NHOR7、C
(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR7、C
(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；
R5, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R5In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R8、
OR8、SR8、S(O)R8、SO2R8、NHR8、N(R8)2、C(O)R8、C(O)NH2、C(O)NHR8、C(O)N(R8)2、NHC(O)R8、NR8C
(O)R8、NHSO2R8、NHC(O)OR8、SO2NH2、SO2NHR8、SO2N(R8)2、NHC(O)NH2、NHC(O)NHR8、OH、(O)、C(O)
OH、N3、CN、NH2, F, Cl, Br and I；
R6, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R6In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R9、
OR9、SR9、S(O)R9、SO2R9、NHR9、N(R9)2、C(O)R9、C(O)NH2、C(O)NHR9、C(O)N(R9)2、NHC(O)R9、NR9C
(O)R9、NHSO2R9、NHC(O)OR9、SO2NH2、SO2NHR9、SO2N(R9)2、NHC(O)NH2、NHC(O)NHR9、OH、(O)、C(O)
OH、N3、CN、NH2、CF3、CF2CF3, F, Cl, Br and I；
R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R8, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R9, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein by R4、R5、R6、R7、R8And R9The cyclic group of expression is independently optionally independently selected by one or more from
Following substitution base substitution：R10、OR10、SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)
R10、OC(O)OR10、NH2、NHR10、N(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)
OR10、NR10C(O)OR10、NHC(O)NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、
C(O)NH2、C(O)NHR10、C(O)N(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、
SO2NH2、SO2NHR10、SO2N(R10)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、
OH、CN、N3、NO2, F, Cl, Br and I；
R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R10In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)OR11、NH2、NHR11、N(R11)2、NHC(O)
R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C(O)OR11、NHC(O)NH2、NHC(O)
NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C(O)NHR11、C(O)N(R11)2、C(O)
NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、SO2NHR11、SO2N(R11)2、C(O)H、C(O)
OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R10
In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group be each optionally independently selected by one or more from following substitution base substitution：
R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、OC(O)OR12、NH2、NHR12、N(R12)2、
NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、NR12C(O)OR12、NHC(O)NH2、NHC
(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)NH2、C(O)NHR12、C(O)N(R12)2、C
(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、SO2NHR12、SO2N(R12)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In aryl, heterocyclic radical, ring
Alkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；With
R12, it is the alkyl of independent selection when occurring every time.
In an embodiment of formula (IIA), X1It is N and X2It is CR1.In another embodiment of formula (IIA),
X1It is CR1And X2It is N.In another embodiment of formula (IIA), X1It is CR1And X2It is CR1.In another reality of formula (IIA)
In applying scheme, X1It is CR1, X2It is CR1And R1When occurring every time independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxyl
Base alkyl, alkoxy, OH, NH2、CN、NO2, F, Cl, Br and I.In another embodiment of formula (IIA), X1It is CR1, X2For
CR1, and R1When occurring every time independently selected from hydrogen, alkyl, F, Cl, Br and I.In another embodiment of formula (IIA),
X1It is CR1, X2It is CR1, and R1It is hydrogen when occurring every time.
In an embodiment of formula (IIA), R1, when occurring every time, independently selected from hydrogen, alkyl, alkenyl, alkynes
Base, haloalkyl, hydroxy alkyl, alkoxy, OH, NH2、CN、NO2, F, Cl, Br and I.In another embodiment of formula (IIA)
In, R1, when occurring every time, independently selected from hydrogen, alkyl, F, Cl, Br and I.In another embodiment of formula (IIA),
R1, when occurring every time, independently selected from hydrogen, alkyl, F and Cl.In another embodiment of formula (IIA), R1Going out every time
It is now hydrogen.
In an embodiment of formula (IIA), R2Independently selected from C4-C6- alkyl, C4-C6- alkenyl, C4-C6- alkynyl,
Aryl, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group；Wherein R2In C4-C6- alkyl, C4-C6- alkenyl and C4-C6- alkynyl is each
Replace from following substitution base is independently selected by one or more from：R3、OR3、SR3、S(O)R3、SO2R3、C(O)R3、CO(O)R3、
OC(O)R3、OC(O)OR3、NH2、NHR3、N(R3)2、NHC(O)R3、NR3C(O)R3、NHS(O)2R3、NR3S(O)2R3、NHC(O)
OR3、NR3C(O)OR3、NHC(O)NH2、NHC(O)NHR3、NHC(O)N(R3)2、NR3C(O)NHR3、NR3C(O)N(R3)2、C(O)
NH2、C(O)NHR3、C(O)N(R3)2、C(O)NHOH、C(O)NHOR3、C(O)NHSO2R3、C(O)NR3SO2R3、SO2NH2、
SO2NHR3、SO2N(R3)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR3、C(N)N(R3)2、CNOH、CNOCH3、OH、(O)、
CN、N3、NO2, F, Cl, Br and I；Wherein R2In aryl, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group each optionally by one
Or multiple replaces independently selected from following substitution base：R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、
OC(O)OR4、NH2、NHR4、N(R4)2、NHC(O)R4、NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)
OR4、NHC(O)NH2、NHC(O)NHR4、NHC(O)N(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、
C(O)N(R4)2、C(O)NHOH、C(O)NHOR4、C(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C
(O)H、C(O)OH、C(N)NH2、C(N)NHR4、C(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.
In another embodiment of formula (IIA), R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl is each
It is independently selected by one or more from following substitution base substitution：R3, F, Cl, Br and I；Wherein R2In the respective optional quilt of aryl
One or more replace independently selected from following substitution base：R4、OR4、CO(O)R4、C(O)NHR4, CN, F, Cl, Br and I.
In another embodiment of formula (IIA), R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl is each
By one or more R3Substitution；Wherein R2In aryl be each optionally independently selected by one or more from following substitution base and take
Generation：R4、OR4、CO(O)R4、C(O)NHR4And CN.In another embodiment of formula (IIA), R2It is C4-C6- alkyl；Wherein R2
In C4-C6- alkyl is each by one or more R3Substitution.In another embodiment of formula (IIA), R2It is aryl；Wherein
R2In aryl be each independently selected by one or more from following substitution base substitution：R4、OR4、CO(O)R4、C(O)NHR4With
CN.In another embodiment of formula (IIA), R2It is aryl；Wherein R2In aryl each by C (O) NHR4Substitution.
In another embodiment of formula (IIA), R2It is phenyl；Wherein R2In phenyl each by C (O) NHR4Substitution.In formula
(IIA) in another embodiment, R2It is phenyl；Wherein R2In phenyl each by an OR4Substitution.In the another of formula (IIA)
In one embodiment, R2It is phenyl；Wherein R2In phenyl each by a R4Substitution.
In an embodiment of formula (IIA), R3, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, cycloalkyl, cycloalkenyl group and heterocyclic radical；Wherein R3In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R5、OR5、SR5、S(O)R5、SO2R5、C(O)R5、CO(O)R5、OC(O)R5、OC(O)OR5、NH2、
NHR5、N(R5)2、NHC(O)R5、NR5C(O)R5、NHS(O)2R5、NR5S(O)2R5、NHC(O)OR5、NR5C(O)OR5、NHC(O)
NH2、NHC(O)NHR5、NHC(O)N(R5)2、NR5C(O)NHR5、NR5C(O)N(R5)2、C(O)NH2、C(O)NHR5、C(O)N
(R5)2、C(O)NHOH、C(O)NHOR5、C(O)NHSO2R5、C(O)NR5SO2R5、SO2NH2、SO2NHR5、SO2N(R5)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR5、C(N)N(R5)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R3
In aryl, cycloalkyl, cycloalkenyl group and heterocyclic radical be each optionally independently selected by one or more from following substitution base substitution：
R6、OR6、SR6、S(O)R6、SO2R6、C(O)R6、CO(O)R6、OC(O)R6、OC(O)OR6、NH2、NHR6、N(R6)2、NHC(O)R6、
NR6C(O)R6、NHS(O)2R6、NR6S(O)2R6、NHC(O)OR6、NR6C(O)OR6、NHC(O)NH2、NHC(O)NHR6、NHC(O)N
(R6)2、NR6C(O)NHR6、NR6C(O)N(R6)2、C(O)NH2、C(O)NHR6、C(O)N(R6)2、C(O)NHOH、C(O)NHOR6、C
(O)NHSO2R6、C(O)NR6SO2R6、SO2NH2、SO2NHR6、SO2N(R6)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR6、C
(N)N(R6)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.In another embodiment of formula (IIA), R3,
When occurring every time, heterocyclic radical independently is；Wherein R3In heterocyclic radical be each optionally independently selected by one or more from it is as follows
Substitution base substitution：CO(O)R6, F, Cl, Br and I.In another embodiment of formula (IIA), R3, when occurring every time, solely
It is on the spot heterocyclic radical；Wherein R3In heterocyclic radical each optionally by one or more CO (O) R6Substitution.
In an embodiment of formula (IIA), R6, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R6In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R9、OR9、SR9、S(O)R9、SO2R9、NHR9、N(R9)2、C(O)R9、C(O)NH2、C(O)NHR9、
C(O)N(R9)2、NHC(O)R9、NR9C(O)R9、NHSO2R9、NHC(O)OR9、SO2NH2、SO2NHR9、SO2N(R9)2、NHC(O)
NH2、NHC(O)NHR9、OH、(O)、C(O)OH、N3、CN、NH2、CF3、CF2CF3, F, Cl, Br and I.Formula (IIA) another
In embodiment, R6It is alkyl when occurring every time.
In an embodiment of formula (IIA), R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R4In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R7、OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、
NHR7、N(R7)2、NHC(O)R7、NR7C(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)
NH2、NHC(O)NHR7、NHC(O)N(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N
(R7)2、C(O)NHOH、C(O)NHOR7、C(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR7、C(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein
By R4The cyclic group of expression is independently optionally independently selected by one or more from following substitution base substitution：R10、OR10、
SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)R10、OC(O)OR10、NH2、NHR10、N
(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)OR10、NR10C(O)OR10、NHC(O)
NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、C(O)NH2、C(O)NHR10、C(O)N
(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、SO2NH2、SO2NHR10、SO2N(R10)2、C
(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.
In another embodiment of formula (IIA), R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkane
Base is each optionally independently selected by one or more from following substitution base substitution：R7, F, Cl, Br and I；Wherein by R4Represent
Cyclic group is independently optionally independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)
R10、CO(O)R10, F, Cl, Br and I.In another embodiment of formula (IIA), R4It is heterocyclic radical when occurring every time.In formula
(IIA) in another embodiment, R4It is heterocyclic radical when occurring every time；Wherein by R4The cyclic group of expression is independently appointed
Choosing is independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)R10、CO(O)R10、F、Cl、
Br and I.
In an embodiment of formula (IIA), R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group.In another embodiment of formula (IIA), R7, when occurring every time, it independently is
Heterocyclic radical.In another embodiment of formula (IIA), R7It is heterocyclic radical when occurring every time；Wherein by R7The cyclic group of expression
Group is independently optionally independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)R10、CO
(O)R10, F, Cl, Br and I.
In an embodiment of formula (IIA), R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R10In alkyl, alkenyl and alkynyl each optionally by one or more independently
Replace selected from following substitution base：R11、OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)
OR11、NH2、NHR11、N(R11)2、NHC(O)R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C
(O)OR11、NHC(O)NH2、NHC(O)NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C
(O)NHR11、C(O)N(R11)2、C(O)NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、
SO2NHR11、SO2N(R11)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、
CN、N3、NO2, F, Cl, Br and I；Wherein R10In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group each optionally by one or more
Replace independently selected from following substitution base：R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、
OC(O)OR12、NH2、NHR12、N(R12)2、NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、
NR12C(O)OR12、NHC(O)NH2、NHC(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)
NH2、C(O)NHR12、C(O)N(R12)2、C(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、
SO2NHR12、SO2N(R12)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、
N3、NO2, F, Cl, Br and I；R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl
And cycloalkenyl group；Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；R12, it is independent selection when occurring every time
Alkyl.In another embodiment of formula (IIA), R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical
And cycloalkyl；Wherein R10In alkyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、N(R11)2、NHC(O)R11, OH, F, Cl, Br and I；Wherein R10In aryl, heterocyclic radical and cycloalkyl it is each optional
It is independently selected by one or more from following substitution base substitution：R12、C(O)R12, F, Cl, Br and I；R11, when occurring every time,
Independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl each optionally replaced by alkoxy；Wherein R11In
Heterocyclic radical and cycloalkyl are each optionally replaced by alkyl；R12, it is the alkyl of independent selection when occurring every time.In formula (IIA)
In another embodiment, R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10In
Alkyl be each optionally independently selected by one or more from following substitution base substitution：R11、OR11、SR11、N(R11)2、NHC
(O)R11, OH and F；Wherein R10In aryl, heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from it is as follows
Substitution base substitution：R12、C(O)R12And F；R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein
R11In alkyl each optionally replaced by alkoxy；Wherein R11In heterocyclic radical and cycloalkyl each optionally replaced by alkyl；
R12, it is the alkyl of independent selection when occurring every time.
One embodiment of the invention is related to compound or its pharmaceutically acceptable salt, its suppression that can be used as NAMPT
Preparation, the compound has formula (IIA)
Formula (IIA)；
Wherein
X1It is CR1And X2It is CR1；
R1, when occurring every time, independently selected from hydrogen, alkyl, F and Cl；
R2Independently selected from C4-C6- alkyl and aryl；Wherein R2In C4-C6- alkyl is each by one or more R3Take
Generation；Wherein R2In aryl be each optionally independently selected by one or more from following substitution base substitution：R4、OR4、CO(O)
R4、C(O)NHR4And CN；
R3, it is heterocyclic radical when occurring every time；Wherein R3In heterocyclic radical each optionally by one or more CO (O) R6Take
Generation；
R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkyl each optionally by one or
Multiple R7Substitution；
R6, when occurring every time, it independently is alkyl；
R7, when occurring every time, it independently is heterocyclic radical；
Wherein by R4And R7The cyclic group of expression is independently optionally independently selected by one or more from following substitution base
Substitution：R10、C(O)C(O)R10、C(O)R10With CO (O) R10；
R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10In alkyl it is each
Replace from following substitution base is optionally independently selected by one or more from：R11、OR11、SR11、N(R11)2、NHC(O)R11, OH and
F；Wherein R10In aryl, heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from following substitution base and take
Generation：R12、C(O)R12And F；
R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl it is each optional
Replaced by alkoxy；Wherein R11In heterocyclic radical each optionally replaced by alkyl；With
R12, it is the alkyl of independent selection when occurring every time.
Another embodiment is related to the compound with formula (IIA), and it includes
N- [4- ({ 1- [(2S) -2- methylbutyryls base] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } phenyl)
Azetidine -1- formamides；
3- (5- fluorine pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } benzene
Base) azetidine -1- formamides；
N- [4- ({ 1- [(2S) -2- methylbutyryls base] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2R)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (3,3,3- trifluoros propiono) piperidin-4-yl] epoxide } phenyl) azetidin
Alkane -1- formamides；
N- (4- { [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (6- picoline -3- bases)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide }
Phenyl) azetidine -1- formamides；
N- (4- { 1- [(2S) -2- methylbutyryls base] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] -1,2,3,6- tetrahydropyridine -4- bases }
Phenyl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] -1,2,3,6- tetrahydropyridine -4- bases }
Phenyl) azetidine -1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridine -3-
Base) azetidine -1- formamides；
4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) methyl benzoate；
N- (4- cyano-phenyls) -3- (pyridin-3-yl) azetidine -1- formamides；
4- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) butyl] tertiary fourth of piperidines -1- formic acid
Ester；
N- { 4- [1- (2,2- dimethylbutanoyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) -1,2,3,6- tetrahydropyridine -4- bases] phenyl }
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) -1,2,3,6- tetrahydropyridine -4- bases] phenyl }
Azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(methylsulfanyl) acetyl group] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { 1- [3- (methylsulfanyl) propiono] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- { 4- [1- (2- methylpropionyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2R)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2S)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } epoxide)
Phenyl] azetidine -1- formamides；
N- (4- { [1- (2- hydroxy-2-methyls propiono) azetidine -3- bases] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2S)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiophene -2- bases carbonyl) piperidin-4-yl] epoxide } phenyl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiene-3-yl carbonyl) piperidin-4-yl] epoxide } phenyl) azetidine-
1- formamides；
N- [4- ({ 1- [(1- Acetylpiperidin -4- bases) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ 1- [(2- methylcyclopropyl groups) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- ({ 1- [3- (morpholine -4- bases) propiono] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ 1- [3- (4- methylpiperazine-1-yls) propiono] piperidin-4-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [3- (pyrrolidin-1-yl) propiono] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
N- (4- { [1- (Cyclopropyl-acetyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (3- methylvaleryls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (4- methylvaleryls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [(1- bytyries piperidin-4-yl) epoxide] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (Ethoxyacetyl base) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (cyclopropyl carbonyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (Methoxyacetyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [(tetrahydrofuran -3- ylmethyls) carbamoyl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2- methylpropionyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- (1- benzoyl piperidine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] tertiary fourth of pyrrolidines -1- formic acid
Ester；
(3R) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1-
T-butyl formate；
(3S) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1-
T-butyl formate；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] azetidine -1- formic acid
The tert-butyl ester；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] azetidine -1- first
Tert-butyl acrylate；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] phenyl } azepine
Cyclobutane -1- formamides；
N- { 4- [1- (2- methylpropionyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } phenyl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } phenyl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] phenyl } azetidine -
1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- benzoyl pyrrole compound alkane -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { 1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- [4- (1- bytyries pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] oxygen
Base } phenyl) azetidine -1- formamides；
N- (4- { [(3R) -1- (2- methylpropionyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3R) -1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3R) -1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- benzoyl pyrrole compound alkane -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (cyclopropyl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ (3R) -1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- bytyries pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] oxygen
Base } phenyl) azetidine -1- formamides；
N- (4- { [(3S) -1- (2- methylpropionyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3S) -1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3S) -1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3S) -1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3S) -1- benzoyl pyrrole compound alkane -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- (cyclopropyl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ (3S) -1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- bytyries pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) azetidine -3- bases] phenyl }
Azetidine -1- formamides；
N- { 4- [1- (2- methylpropionyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } phenyl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } phenyl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- (1- benzoyl azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) azetidine -3- bases] phenyl } azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { 1- [(2S) -2- methylbutyryls base] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- (1- bytyry azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
4- [4- ({ [3- (2- chloropyridine -3- bases) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester；
4- [4- ({ [3- (4- chloropyridine -3- bases) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester；
N- (4- { [1- (Cyclopropyl-acetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (furans -2- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
4- [4- ({ [3- (2- fluorine pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester；
N- { 4- [(1- valeryl azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- ({ 1- [(2- methoxy ethoxies) acetyl group] azetidine -3- bases } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { [1- (Ethoxyacetyl base) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (Methoxyacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (3- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] azetidine -3- bases } epoxide) benzene
Base] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { [1- (2,3- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (4- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(2- methylcyclopropyl groups) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (4,4,4- trifluoros bytyry) azetidine -3- bases] epoxide } phenyl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (2- methylpropionyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [(1- bytyry azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [(1- propiono azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (2,2- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (3- methylbutyryls base) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (3,3,3- trifluoros propiono) azetidine -3- bases] epoxide } phenyl) nitrogen
Azetidine -1- formamides；
N- [4- ({ 1- [(1- methylcyclopropyl groups) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [1- (2- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [(1- acetyl group azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (Cyclohexylacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (cyclohexyl-carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (cyclopropyl carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiophene -2- bases carbonyl) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- (4- { [1- (cyclopentylcarbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (morpholine -4- bases acetyl group) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazole -5- bases carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
N- [4- ({ 1- [(3,5- dimethyl -1,2- oxazole -4- bases) carbonyl] azetidine -3- bases } epoxide) phenyl] -
3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiene-3-yl carbonyl) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazole-4-yls carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [1- (1,2- oxazole -5- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ 1- [(4- methylpiperazine-1-yls) acetyl group] azetidine -3- bases } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { [1- (N, N- dimethyl-β-alanyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [1- (furans -3- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ 1- [(1- methylcyclohexyls) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [1- (Cyclopentylacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazol-2-yls carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (pyrrolidin-1-yl acetyl group) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
3- (2- fluorine pyridin-3-yl)-N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2- methyl-propyls) -1H- pyrazoles -4- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- [4- (1- propyl group -1H- pyrazoles -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(3S)-tetrahydrofuran -3- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
3- (4- chloropyridine -3- bases)-N- (4- { 1- [(3S)-tetrahydrofuran -3- bases carbonyl] piperidin-4-yl } phenyl) azepine
Cyclobutane -1- formamides；
3- (2- chloropyridine -3- bases)-N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } azacyclo-
Butane -1- formamides；
N- [4- (1- valeryls piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] piperidin-4-yl } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (4- methylvaleryls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylvaleryls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- ethoxy-cs acyl group) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2,2- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- (1- bytyries piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylbutyryls base) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (N- acetyl group-L- leucyl-s) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclohexyl-carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Cyclohexylacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (cyclopentylcarbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (furans -3- bases carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- (1- Acetylpiperidin -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- (1- propionos piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (pyrrolidin-1-yl acetyl group) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (Cyclopentylacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- (1- valeryl azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] azetidine -3- bases } phenyl) -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- { 4- [1- (4- methylvaleryls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- methylvaleryls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- ethoxy-cs acyl group) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- Dimethylpropanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- methylbutyryls base) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (N- acetyl group-L- leucyl-s) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (cyclohexyl-carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (Cyclohexylacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) azetidine -3- bases] phenyl } azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopentylcarbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [1- (furans -3- bases carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- [4- (1- acetyl group azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- (1- propiono azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopentylacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2,3- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopentyl-methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (cyclohexyl methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- methyl amyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- methyl-propyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methyl butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- ethyl-butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2,2- dimethyl propyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- methyl butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- butyl piperidine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- propylpiperdine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- cyclopropylethyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- ylmethyls) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (2,2- dimethylbutyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclopentyl-methyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (cyclohexyl methyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3,3- dimethylbutyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Cvclopropvlmethvl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2- methyl amyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -2- ylmethyls) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2- methyl-propyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3- methyl butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2- ethyl-butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2,2- dimethyl propyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2- methyl butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- ylmethyls) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2,2- dimethylbutyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- valeryls pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methylvaleryls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
N- { 4- [1- (Cyclopentylacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (furans -3- bases carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (pyrrolidin-1-yl acetyl group) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- { 4- [1- (N, N- dimethyl-β-alanyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- (4- { 1- [(4- methylpiperazine-1-yls) acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- { 4- [1- (5- oxo-L-prolyls base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- ethoxy-cs acyl group) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (4- methylvaleryls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- acetyl-pyrrolidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Cyclohexylacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- [4- (1- propionos pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { 1- [3- (morpholine -4- bases) propiono] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- Dimethylpropanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [3- (piperidin-1-yl) propiono] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (3,3- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2,2- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2- oxos propiono) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (Methoxyacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclohexyl-carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylbutyryls base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclopentylcarbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2,3- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [(3R) -1- valeryls pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [(3R) -1- (3- methylvaleryls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [1- (two rings [2.2.1] hept- 2- bases acetyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclopentylacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(2- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (morpholine -4- bases acetyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (furans -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (pyrrolidin-1-yl acetyl group) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (5- oxo-D- prolyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (N, N- dimethyl-β-alanyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (1,3- thiazol-2-yls carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (thiene-3-yl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- ({ (3R) -1- [(3 methyl thiophene -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (4,4,4- trifluoros bytyry) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- [4- ({ (3R) -1- [(4- methylpiperazine-1-yls) acetyl group] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- (4- { [(3R) -1- (5- oxo-L-prolyls base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (3- ethoxy-cs acyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (4- methylvaleryls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methylcyclohexyls) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclohexylacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (N- acetyl group-L- leucyl-s) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- propionos pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- ({ (3R) -1- [(2- methoxy ethoxies) acetyl group] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- [4- ({ (3R) -1- [3- (morpholine -4- bases) propiono] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (2,2- Dimethylpropanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ (3R) -1- [(5- methylthiophene -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (thiophene -2- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- (4- { [(3R) -1- (furans -2- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [3- (piperidin-1-yl) propiono] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Ethoxyacetyl base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (3,3- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (2,2- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (Methoxyacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (cyclohexyl-carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [(3R) -1- (3- methylbutyryls base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (cyclopentylcarbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [(3R) -1- (2,3- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- (1- benzoyl piperidine -4- bases) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides；
N- { 4- [1- (2- fluoro benzoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine；
N- { 4- [1- (2- methyl benzoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- first
Acid amides；
N- { 4- [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1-
Formamide；
N- { 4- [1- (cyclopropyl carbonyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- [4- (1- Acetylpiperidin -4- bases) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1-
Formamide；
N- { 4- [1- (cyclobutyl carbonyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
3- (pyridazine -3- bases)-N- { 4- [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- (pyridazine -3- bases)-N- { 4- [1- (3,3,3- trifluoros propiono) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine；
N- { 4- [(1- benzoyl piperidine -4- bases) methyl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine；
N- (4- { [1- (2- fluoro benzoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidin
Alkane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidin
Alkane -1- formamides；
N- (4- { [1- (2- ethylbutanoyls base) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
3- (pyridazine -3- bases)-N- (4- { [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] methyl } phenyl) azetidin
Alkane -1- formamides；
N- (4- { [1- (2- methylpropionyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- { 4- [(1- Acetylpiperidin -4- bases) methyl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- [4- ({ 1- [(2S) -2- methylbutyryls base] piperidin-4-yl } methyl) phenyl] -3- (pyridazine -3- bases) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } methyl) phenyl] -3- (pyridazine -3- bases) azacyclo-
Butane -1- formamides；With its pharmaceutically acceptable salt.
The embodiment of formula (IIIA)
On the other hand, offer formula (IIIA) compound of the present invention
(IIIA)；
With its pharmaceutically acceptable salt；Wherein work as R2During for aryl in formula (IA), R4xSuch as herein for R2On
Described in substitution base.
One embodiment of the invention is related to formula (IIIA) compound or its pharmaceutically acceptable salt；
Wherein
R4xIndependently selected from R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、OC(O)OR4、
NH2、NHR4、N(R4)2、NHC(O)R4、NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)OR4、NHC
(O)NH2、NHC(O)NHR4、NHC(O)N(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、C(O)N
(R4)2、C(O)NHOH、C(O)NHOR4、C(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR4、C(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R4In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R7、
OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、NHR7、N(R7)2、NHC(O)R7、NR7C
(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)NH2、NHC(O)NHR7、NHC(O)N
(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N(R7)2、C(O)NHOH、C(O)NHOR7、C
(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR7、C
(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；
R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein by R4And R7The cyclic group of expression is independently optionally independently selected by one or more from following substitution base
Substitution：R10、OR10、SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)R10、OC(O)OR10、
NH2、NHR10、N(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)OR10、NR10C(O)
OR10、NHC(O)NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、C(O)NH2、C(O)
NHR10、C(O)N(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、SO2NH2、SO2NHR10、
SO2N(R10)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、OH、CN、N3、NO2、F、
Cl, Br and I；
R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R10In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)OR11、NH2、NHR11、N(R11)2、NHC(O)
R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C(O)OR11、NHC(O)NH2、NHC(O)
NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C(O)NHR11、C(O)N(R11)2、C(O)
NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、SO2NHR11、SO2N(R11)2、C(O)H、C(O)
OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R10
In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group be each optionally independently selected by one or more from following substitution base substitution：
R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、OC(O)OR12、NH2、NHR12、N(R12)2、
NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、NR12C(O)OR12、NHC(O)NH2、NHC
(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)NH2、C(O)NHR12、C(O)N(R12)2、C
(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、SO2NHR12、SO2N(R12)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In aryl, heterocyclic radical, ring
Alkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；With
R12, it is the alkyl of independent selection when occurring every time.
In an embodiment of formula (IIIA), R4xIndependently selected from R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、
CO(O)R4、OC(O)R4、OC(O)OR4、NH2、NHR4、N(R4)2、NHC(O)R4、NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、
NHC(O)OR4、NR4C(O)OR4、NHC(O)NH2、NHC(O)NHR4、NHC(O)N(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、
C(O)NH2、C(O)NHR4、C(O)N(R4)2、C(O)NHOH、C(O)NHOR4、C(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、
SO2NHR4、SO2N(R4)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR4、C(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、
NO2, F, Cl, Br and I.In another embodiment of formula (IIIA), R4xIndependently selected from R4、OR4、CO(O)R4、C(O)
NHR4, CN, F, Cl, Br and I.In another embodiment of formula (IIIA), R4xIndependently selected from R4、OR4、CO(O)R4、C
(O)NHR4And CN.In another embodiment of formula (IIIA), R4xIt is C (O) NHR4.In another implementation of formula (IIIA)
In scheme, R4xIt is OR4.In another embodiment of formula (IIIA), R4xIt is R4。
In an embodiment of formula (IIIA), R4, every time occur when, independently selected from alkyl, alkenyl, alkynyl,
Aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R4In alkyl, alkenyl and alkynyl each optionally by one or more independences
Ground replaces selected from following substitution base：R7、OR7、SR7、S(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、
NH2、NHR7、N(R7)2、NHC(O)R7、NR7C(O)R7、NHS(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC
(O)NH2、NHC(O)NHR7、NHC(O)N(R7)2、NR7C(O)NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N
(R7)2、C(O)NHOH、C(O)NHOR7、C(O)NHSO2R7、C(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C
(O)OH、C(N)NH2、C(N)NHR7、C(N)N(R7)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein
By R4The cyclic group of expression is independently optionally independently selected by one or more from following substitution base substitution：R10、OR10、
SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)R10、OC(O)OR10、NH2、NHR10、N
(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)OR10、NR10C(O)OR10、NHC(O)
NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、C(O)NH2、C(O)NHR10、C(O)N
(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、SO2NH2、SO2NHR10、SO2N(R10)2、C
(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I.
In another embodiment of formula (IIIA), R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkane
Base is each optionally independently selected by one or more from following substitution base substitution：R7, F, Cl, Br and I；Wherein by R4Represent
Cyclic group is independently optionally independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)
R10、CO(O)R10, F, Cl, Br and I.In another embodiment of formula (IIIA), R4, it is heterocyclic radical when occurring every time.
In another embodiment of formula (IIIA), R4, it is heterocyclic radical when occurring every time；Wherein by R4The cyclic group of expression
Independently optionally it is independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)R10、CO(O)
R10, F, Cl, Br and I.
In an embodiment of formula (IIIA), R7, every time occur when, independently selected from alkyl, alkenyl, alkynyl,
Aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group.In another embodiment of formula (IIIA), R7, it is independent when occurring every time
Ground is heterocyclic radical.In another embodiment of formula (IIIA), R7It is heterocyclic radical when occurring every time；Wherein by R7Represent
Cyclic group is independently optionally independently selected by one or more from following substitution base substitution：R10、C(O)C(O)R10、C(O)
R10、CO(O)R10, F, Cl, Br and I.
In an embodiment of formula (IIIA), R10, every time occur when, independently selected from alkyl, alkenyl, alkynyl,
Aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R10In alkyl, alkenyl and alkynyl each optionally by one or more independences
Ground replaces selected from following substitution base：R11、OR11、SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)
OR11、NH2、NHR11、N(R11)2、NHC(O)R11、NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C
(O)OR11、NHC(O)NH2、NHC(O)NHR11、NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C
(O)NHR11、C(O)N(R11)2、C(O)NHOH、C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、
SO2NHR11、SO2N(R11)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、
CN、N3、NO2, F, Cl, Br and I；Wherein R10In aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group each optionally by one or more
Replace independently selected from following substitution base：R12、OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、
OC(O)OR12、NH2、NHR12、N(R12)2、NHC(O)R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、
NR12C(O)OR12、NHC(O)NH2、NHC(O)NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)
NH2、C(O)NHR12、C(O)N(R12)2、C(O)NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、
SO2NHR12、SO2N(R12)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、
N3、NO2, F, Cl, Br and I；R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl
And cycloalkenyl group；Wherein R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group are each optionally replaced by alkyl or alkoxy；R12, it is independent selection when occurring every time
Alkyl.In another embodiment of formula (IIIA), R10, when occurring every time, independently selected from alkyl, aryl, heterocycle
Base and cycloalkyl；Wherein R10In alkyl be each optionally independently selected by one or more from following substitution base substitution：R11、
OR11、SR11、N(R11)2、NHC(O)R11, OH, F, Cl, Br and I；Wherein R10In aryl, heterocyclic radical and cycloalkyl it is each optional
It is independently selected by one or more from following substitution base substitution：R12、C(O)R12, F, Cl, Br and I；R11, when occurring every time,
Independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl each optionally replaced by alkoxy；Wherein R11In
Heterocyclic radical and cycloalkyl are each optionally replaced by alkyl；R12, it is the alkyl of independent selection when occurring every time.At formula (IIIA)
Another embodiment in, R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10
In alkyl be each optionally independently selected by one or more from following substitution base substitution：R11、OR11、SR11、N(R11)2、NHC
(O)R11, OH and F；Wherein R10In aryl, heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from it is as follows
Substitution base substitution：R12、C(O)R12And F；R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein
R11In alkyl each optionally replaced by alkoxy；Wherein R11In heterocyclic radical and cycloalkyl each optionally replaced by alkyl；
R12, it is the alkyl of independent selection when occurring every time.
One embodiment of the invention is related to compound or its pharmaceutically acceptable salt, its suppression that can be used as NAMPT
Preparation, the compound has formula (IIIA)
Formula (IIIA)；
Wherein
R4x Independently selected from R4、OR4、CO(O)R4、C(O)NHR4And CN；
R4, when occurring every time, independently selected from alkyl and heterocyclic radical；Wherein R4In alkyl each optionally by one or
Multiple R7Substitution；
R7, when occurring every time, it independently is heterocyclic radical；
Wherein by R4And R7The cyclic group of expression is independently optionally independently selected by one or more from following substitution base
Substitution：R10、C(O)C(O)R10、C(O)R10With CO (O) R10；
R10, when occurring every time, independently selected from alkyl, aryl, heterocyclic radical and cycloalkyl；Wherein R10In alkyl it is each
Replace from following substitution base is optionally independently selected by one or more from：R11、OR11、SR11、N(R11)2、NHC(O)R11, OH and
F；Wherein R10In aryl, heterocyclic radical and cycloalkyl be each optionally independently selected by one or more from following substitution base and take
Generation：R12、C(O)R12And F；
R11, when occurring every time, independently selected from alkyl, heterocyclic radical and cycloalkyl；Wherein R11In alkyl it is each optional
Replaced by alkoxy；Wherein R11In heterocyclic radical each optionally replaced by alkyl；With
R12, it is the alkyl of independent selection when occurring every time.
Another embodiment is related to the compound with formula (IIIA), and it includes
N- [4- ({ 1- [(2S) -2- methylbutyryls base] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- [4- ({ 1- [(2S) -2- methylbutyryls base] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2R)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (3,3,3- trifluoros propiono) piperidin-4-yl] epoxide } phenyl) azetidin
Alkane -1- formamides；
N- (4- { [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(2S) -2- methylbutyryls base] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] -1,2,3,6- tetrahydropyridine -4- bases }
Phenyl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] -1,2,3,6- tetrahydropyridine -4- bases }
Phenyl) azetidine -1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridine -3-
Base) azetidine -1- formamides；
4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) methyl benzoate；
N- (4- cyano-phenyls) -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2,2- dimethylbutanoyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) -1,2,3,6- tetrahydropyridine -4- bases] phenyl }
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) -1,2,3,6- tetrahydropyridine -4- bases] phenyl }
Azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(methylsulfanyl) acetyl group] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { 1- [3- (methylsulfanyl) propiono] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- { 4- [1- (2- methylpropionyls) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2R)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2S)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } epoxide)
Phenyl] azetidine -1- formamides；
N- (4- { [1- (2- hydroxy-2-methyls propiono) azetidine -3- bases] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2S)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiophene -2- bases carbonyl) piperidin-4-yl] epoxide } phenyl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiene-3-yl carbonyl) piperidin-4-yl] epoxide } phenyl) azetidine-
1- formamides；
N- [4- ({ 1- [(1- Acetylpiperidin -4- bases) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ 1- [(2- methylcyclopropyl groups) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- ({ 1- [3- (morpholine -4- bases) propiono] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ 1- [3- (4- methylpiperazine-1-yls) propiono] piperidin-4-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [3- (pyrrolidin-1-yl) propiono] piperidin-4-yl } epoxide) phenyl] nitrogen
Azetidine -1- formamides；
N- (4- { [1- (Cyclopropyl-acetyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (3- methylvaleryls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (4- methylvaleryls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [(1- bytyries piperidin-4-yl) epoxide] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (Ethoxyacetyl base) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (cyclopropyl carbonyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (Methoxyacetyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [(tetrahydrofuran -3- ylmethyls) carbamoyl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2- methylpropionyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- (1- benzoyl piperidine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] tertiary fourth of pyrrolidines -1- formic acid
Ester；
(3R) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1-
T-butyl formate；
(3S) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1-
T-butyl formate；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] azetidine -1- formic acid
The tert-butyl ester；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] azetidine -1- first
Tert-butyl acrylate；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] phenyl } azepine
Cyclobutane -1- formamides；
N- { 4- [1- (2- methylpropionyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } phenyl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } phenyl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] phenyl } azetidine -
1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- benzoyl pyrrole compound alkane -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { 1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- [4- (1- bytyries pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] oxygen
Base } phenyl) azetidine -1- formamides；
N- (4- { [(3R) -1- (2- methylpropionyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3R) -1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3R) -1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- benzoyl pyrrole compound alkane -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (cyclopropyl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ (3R) -1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- bytyries pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] oxygen
Base } phenyl) azetidine -1- formamides；
N- (4- { [(3S) -1- (2- methylpropionyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3S) -1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3S) -1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide)
Phenyl] azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3S) -1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3S) -1- benzoyl pyrrole compound alkane -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (3,3,3- trifluoros propiono) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- (cyclopropyl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ (3S) -1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3S) -1- bytyries pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) azetidine -3- bases] phenyl }
Azetidine -1- formamides；
N- { 4- [1- (2- methylpropionyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } phenyl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } phenyl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- (1- benzoyl azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoros propiono) azetidine -3- bases] phenyl } azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { 1- [(2S) -2- methylbutyryls base] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- (1- bytyry azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { [1- (Cyclopropyl-acetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (furans -2- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- { 4- [(1- valeryl azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- ({ 1- [(2- methoxy ethoxies) acetyl group] azetidine -3- bases } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { [1- (Ethoxyacetyl base) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (Methoxyacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (3- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] azetidine -3- bases } epoxide) benzene
Base] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { [1- (2,3- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (4- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(2- methylcyclopropyl groups) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (4,4,4- trifluoros bytyry) azetidine -3- bases] epoxide } phenyl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (2- methylpropionyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [(1- bytyry azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [(1- propiono azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (2,2- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [1- (3- methylbutyryls base) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (3,3,3- trifluoros propiono) azetidine -3- bases] epoxide } phenyl) nitrogen
Azetidine -1- formamides；
N- [4- ({ 1- [(1- methylcyclopropyl groups) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [1- (2- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [(1- acetyl group azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [1- (Cyclohexylacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (cyclohexyl-carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (cyclopropyl carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiophene -2- bases carbonyl) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- (4- { [1- (cyclopentylcarbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (morpholine -4- bases acetyl group) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazole -5- bases carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
N- [4- ({ 1- [(3,5- dimethyl -1,2- oxazole -4- bases) carbonyl] azetidine -3- bases } epoxide) phenyl] -
3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiene-3-yl carbonyl) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazole-4-yls carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [1- (1,2- oxazole -5- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ 1- [(4- methylpiperazine-1-yls) acetyl group] azetidine -3- bases } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { [1- (N, N- dimethyl-β-alanyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [1- (furans -3- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ 1- [(1- methylcyclohexyls) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [1- (Cyclopentylacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3- thiazol-2-yls carbonyl) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (pyrrolidin-1-yl acetyl group) azetidine -3- bases] epoxide } phenyl)
Azetidine -1- formamides；
N- { 4- [1- (2- methyl-propyls) -1H- pyrazoles -4- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- [4- (1- propyl group -1H- pyrazoles -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(3S)-tetrahydrofuran -3- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
N- [4- (1- valeryls piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] piperidin-4-yl } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (4- methylvaleryls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylvaleryls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- ethoxy-cs acyl group) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2,2- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- (1- bytyries piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylbutyryls base) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (N- acetyl group-L- leucyl-s) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclohexyl-carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Cyclohexylacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (cyclopentylcarbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (furans -3- bases carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- (1- Acetylpiperidin -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- (1- propionos piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (pyrrolidin-1-yl acetyl group) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (Cyclopentylacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- (1- valeryl azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] azetidine -3- bases } phenyl) -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- { 4- [1- (4- methylvaleryls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- methylvaleryls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- ethoxy-cs acyl group) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- Dimethylpropanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- methylbutyryls base) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (N- acetyl group-L- leucyl-s) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (cyclohexyl-carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (Cyclohexylacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) azetidine -3- bases] phenyl } azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopentylcarbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [1- (furans -3- bases carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- [4- (1- acetyl group azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- (1- propiono azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (Cyclopentylacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2,3- dimethylbutanoyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (cyclopentyl-methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (cyclohexyl methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- methyl amyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- methyl-propyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methyl butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- ethyl-butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2,2- dimethyl propyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- methyl butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- butyl piperidine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- propylpiperdine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- cyclopropylethyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- ylmethyls) piperidin-4-yl] phenyl } azetidine -1-
Formamide；
N- { 4- [1- (2,2- dimethylbutyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclopentyl-methyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (cyclohexyl methyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3,3- dimethylbutyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Cvclopropvlmethvl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2- methyl amyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -2- ylmethyls) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2- methyl-propyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (3- methyl butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2- ethyl-butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2,2- dimethyl propyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2- methyl butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- ylmethyls) azetidine -3- bases] phenyl } azacyclo-
Butane -1- formamides；
N- { 4- [1- (2,2- dimethylbutyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- valeryls pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methylvaleryls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
N- { 4- [1- (Cyclopentylacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (furans -3- bases carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (pyrrolidin-1-yl acetyl group) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- { 4- [1- (N, N- dimethyl-β-alanyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (1,3- thiazol-2-yls carbonyl) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoros bytyry) pyrrolidin-3-yl] phenyl } azetidine-
1- formamides；
N- (4- { 1- [(4- methylpiperazine-1-yls) acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- { 4- [1- (5- oxo-L-prolyls base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3- ethoxy-cs acyl group) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (4- methylvaleryls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- acetyl-pyrrolidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Cyclohexylacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- [4- (1- propionos pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { 1- [3- (morpholine -4- bases) propiono] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (2,2- Dimethylpropanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [3- (piperidin-1-yl) propiono] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (3,3- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2,2- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2- oxos propiono) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (Methoxyacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclohexyl-carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methylbutyryls base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (cyclopentylcarbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2,3- dimethylbutanoyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [(3R) -1- valeryls pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { [(3R) -1- (3- methylvaleryls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [1- (two rings [2.2.1] hept- 2- bases acetyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclopentylacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(2- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (morpholine -4- bases acetyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (furans -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (pyrrolidin-1-yl acetyl group) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (5- oxo-D- prolyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (N, N- dimethyl-β-alanyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (1,3- thiazol-2-yls carbonyl) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (thiene-3-yl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- ({ (3R) -1- [(3 methyl thiophene -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (4,4,4- trifluoros bytyry) pyrrolidin-3-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- [4- ({ (3R) -1- [(4- methylpiperazine-1-yls) acetyl group] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- (4- { [(3R) -1- (5- oxo-L-prolyls base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (3- ethoxy-cs acyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (4- methylvaleryls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methylcyclohexyls) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclohexylacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (N- acetyl group-L- leucyl-s) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- propionos pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- ({ (3R) -1- [(2- methoxy ethoxies) acetyl group] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- [4- ({ (3R) -1- [3- (morpholine -4- bases) propiono] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (2,2- Dimethylpropanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- [4- ({ (3R) -1- [(5- methylthiophene -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (thiophene -2- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
N- (4- { [(3R) -1- (furans -2- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [3- (piperidin-1-yl) propiono] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (Ethoxyacetyl base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (3,3- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (2,2- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [(3R) -1- (Methoxyacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (cyclohexyl-carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [(3R) -1- (3- methylbutyryls base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (cyclopentylcarbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [(3R) -1- (2,3- dimethylbutanoyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；With its pharmaceutically acceptable salt.
Pharmaceutical composition, combination treatment, treatment method and administration
Another embodiment includes containing compound and the pharmaceutical composition of excipient with formula (I).
Another embodiment includes the method for the cancer for the treatment of mammal, and it includes that giving treatment to mammal can connect
The compound with formula (I) measured.
Another embodiment is related to treat the composition of the disease that NAMPT is expressed during disease, and the composition is included
The compound with formula (I) of excipient and therapeutically effective amount.
Another embodiment is related to treat the method for the disease that NAMPT is expressed during disease of patient, methods described bag
Include the compound with formula (I) that therapeutically effective amount is given to the patient.
Another embodiment is related to the composition for treating following disease：Inflammation and tissue repair obstacle；Particularly class
Rheumatic arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fiber become
Property disease；The skin injury of skin disease, including psoriasis, allergic dermatitis and induced by ultraviolet irradiation；Autoimmune disease, bag
Include systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, mandatory rachitis, tissue and organ rejection, alzheimer '
Silent disease, apoplexy, atherosclerosis, ISR, diabetes, glomerulonephritis, cancer, particularly wherein described cancer is selected from
Breast cancer, prostate cancer, lung cancer, colon cancer, cervix cancer, oophoroma, cutaneum carcinoma, CNS cancers, carcinoma of urinary bladder, cancer of pancreas, white blood
Disease, lymthoma or Hodgkin's disease, cachexia, the inflammation related to infection and some viral infections, including acquired immunity
Deficiency symptoms (AIDS), ARDS, and ataxia-telangiectasia, the composition include tax
Shape agent and the compound with formula (I) of therapeutically effective amount.
Another embodiment is related to treat the method for the following disease of patient：Inflammation and tissue repair obstacle；Particularly class
Rheumatic arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fiber become
Property disease；The skin injury of skin disease, including psoriasis, allergic dermatitis and induced by ultraviolet irradiation；Autoimmune disease, bag
Include systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, mandatory rachitis, tissue and organ rejection, alzheimer '
Silent disease, apoplexy, atherosclerosis, ISR, diabetes, glomerulonephritis, cancer, particularly wherein described cancer is selected from
Breast cancer, prostate cancer, lung cancer, colon cancer, cervix cancer, oophoroma, cutaneum carcinoma, CNS cancers, carcinoma of urinary bladder, cancer of pancreas, white blood
Disease, lymthoma or Hodgkin's disease, cachexia, the inflammation related to infection and some viral infections, including acquired immunity
Deficiency symptoms (AIDS), ARDS, and ataxia-telangiectasia, methods described are included to this
Patient gives the compound with formula (I) of therapeutically effective amount.
Another embodiment is related to the composition for treating the disease that NAMPT is expressed during disease, the composition
A kind of additional therapeutic agent of compound with formula (I) and therapeutically effective amount comprising excipient and therapeutically effective amount or more than one
The additional therapeutic agent planted.
Another embodiment is related to the method for the disease that NAMPT is expressed during disease for treating patient, the side
Method include to the patient give the compound with formula (I) of therapeutically effective amount and a kind of additional therapeutic agent of therapeutically effective amount or
More than one additional therapeutic agent.
Another embodiment is related to the composition for treating following disease：Inflammation and tissue repair obstacle；Particularly class
Rheumatic arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fiber become
Property disease；The skin injury of skin disease, including psoriasis, allergic dermatitis and induced by ultraviolet irradiation；Autoimmune disease, bag
Include systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, mandatory rachitis, tissue and organ rejection, alzheimer '
Silent disease, apoplexy, atherosclerosis, ISR, diabetes, glomerulonephritis, cancer, particularly wherein described cancer is selected from
Breast cancer, prostate cancer, lung cancer, colon cancer, cervix cancer, oophoroma, cutaneum carcinoma, CNS cancers, carcinoma of urinary bladder, cancer of pancreas, white blood
Disease, lymthoma or Hodgkin's disease, cachexia, the inflammation related to infection and some viral infections, including acquired immunity
Deficiency symptoms (AIDS), ARDS, and ataxia-telangiectasia, the composition include tax
The compound with formula (I) of shape agent and therapeutically effective amount and a kind of additional therapeutic agent of therapeutically effective amount are more than one attached
With therapeutic agent.
Another embodiment is related to treat the method for the following disease of patient：Inflammation and tissue repair obstacle；Particularly class
Rheumatic arthritis, inflammatory bowel disease, asthma and COPD (chronic obstructive pulmonary disease), osteoarthritis, osteoporosis and fiber become
Property disease；The skin injury of skin disease, including psoriasis, allergic dermatitis and induced by ultraviolet irradiation；Autoimmune disease, bag
Include systemic lupus erythematosus, multiple sclerosis, psoriatic arthritis, mandatory rachitis, tissue and organ rejection, alzheimer '
Silent disease, apoplexy, atherosclerosis, ISR, diabetes, glomerulonephritis, cancer, particularly wherein described cancer is selected from
Breast cancer, prostate cancer, lung cancer, colon cancer, cervix cancer, oophoroma, cutaneum carcinoma, CNS cancers, carcinoma of urinary bladder, cancer of pancreas, white blood
Disease, lymthoma or Hodgkin's disease, cachexia, the inflammation related to infection and some viral infections, including acquired immunity
Deficiency symptoms (AIDS), ARDS, and ataxia-telangiectasia, methods described are included to this
Patient gives the compound with formula (I) of therapeutically effective amount and a kind of additional therapeutic agent or more than one of therapeutically effective amount
Additional therapeutic agent.
By external or internal metabolic process produce the compound with formula (I) metabolin can be used for treatment with
NAMPT related disease.
Can be metabolized in vitro or in vivo can be used for forming some precursor compounds of the compound with formula (I)
The treatment disease related to NAMPT.
Compound with formula (I) can exist with acid-addition salts, base addition salts or zwitterionic form.In the phase of separation
Between or compound purifying after prepare compound salt.The acid-addition salts of compound are derived from the compound and acid reaction
Those.For example, the acetate of the compound, adipate, alginate, bicarbonate, citrate, aspartate,
Benzoate, benzene sulfonate, disulfate, butyrate, camphor hydrochlorate, camsilate, double gluconates, formates, rich horse
Hydrochlorate, glycerophosphate, glutamate, Hemisulphate, enanthate, caproate, hydrochloride, hydrobromate, hydriodate, lactose
Aldehydic acid salt, lactate, maleate, tri-methyl p-toluenesulfonate salt, mesylate, naphthalene sulfonate, nicotinate, oxalates, double hydroxyl naphthalenes
Hydrochlorate, pectate, persulfate, phosphate, picrate, propionate, succinate, tartrate, rhodanate, trichlorine
Acetate, trifluoroacetate, tosilate and hendecane hydrochlorate are to be considered as included in the present invention.The compound
Base addition salts are derived from the compound and the cation such as hydroxide of lithium, sodium, potassium, calcium and magnesium, carbonate or bicarbonate
Reaction those.
Can it is for example buccal, through eye, oral, infiltration, parenteral（Intramuscular, intraperitoneal, breastbone are interior, intravenous, subcutaneous）, it is straight
Intestines, part, percutaneous or vagina give the compound with formula (I).
The compound with formula (I) of therapeutically effective amount depends on the recipient for the treatment of, illness to be treated and its is serious
Degree, the composition containing the compound, administration time, method of administration, treatment duration, compound efficacy, its clearance rate
Whether other drugs are given jointly.Give the tool of the composition of patient daily with single dose or with fractionated dose for preparing
The amount for having the compound of the invention of formula (I) is for about 0.03 to about 200 mg/kg body weight.Single dose compositions contain this tittle
Or the combination of its approximate number.
Compound with formula (I) can together be administered with or without excipient.Excipient include for example coating material or
Additive, such as sorbefacient, antioxidant, adhesive, buffer, coating agent, colouring agent, diluent, disintegrant, emulsification
Agent, extender, filler, flavor enhancement, NMF, lubricant, essence, preservative, propellant, releasing agent, disinfectant, sweetener,
Solubilizer, wetting agent and its mixture.
Excipient bag for preparing the composition comprising the compound with formula (I) to be administered orally with solid dosage forms
Include such as agar, alginic acid, aluminium hydroxide, benzylalcohol, Ergol, 1,3 butylene glycol, Carbomer, castor oil, cellulose, acetic acid
Cellulose, cocoa butter, cornstarch, corn oil, cottonseed oil, Crospovidone, diglyceride, ethanol, ethyl cellulose, laurate
Ethyl ester, ethyl oleate, fatty acid ester, gelatin, embryo oil, glucose, glycerine, peanut（groundnut）Oil, hydroxypropyl methyl are fine
Dimension element, isopropanol, isotonic saline solution, lactose, magnesium hydroxide, magnesium stearate, malt, mannitol, monoglyceride, olive oil, peanut
（peanut）Oil, potassium phosphate, farina, PVP, propane diols, Ringer's mixture, safflower oil, sesame oil, carboxymethyl
Sodium cellulosate, sodium ascorbyl phosphate, lauryl sodium sulfate, sorbose sodium alkoxide, soybean oil, stearic acid, sodium stearyl base ester, sugarcane
Sugar, surfactant, talcum, bassora gum, tetrahydrofurfuryl alcohol, triglycerides, water and its mixture.Will be with liquid agent for preparing
Type includes such as 1,3- fourths through the excipient of eye or the composition comprising the compound with formula (I) of the invention of oral administration
Glycol, castor oil, corn oil, cottonseed oil, ethanol, the fatty acid ester of sorbitan, embryo oil, peanut oil, glycerine, isopropyl
Alcohol, olive oil, polyethylene glycol, propane diols, sesame oil, water and its mixture.For prepare want infiltration administration comprising the present invention
The compound with formula (I) composition excipient include such as CFC, ethanol, water and its mixture.For preparing
Wanting the excipient of the composition comprising the compound with formula (I) of the invention of parenteral includes such as 1,3- fourths two
Alcohol, castor oil, corn oil, cottonseed oil, dextrose, embryo oil, peanut（groundnut）Oil, liposome, oleic acid, olive oil, flower
It is raw（peanut）Oil, Ringer's mixture, safflower oil, sesame oil, soybean oil, U.S.P. or isotonic sodium chlorrde solution, water and it is mixed
Compound.Excipient for preparing the composition comprising the compound with formula (I) of the invention for wanting rectum or vagina administration
Including such as cocoa butter, polyethylene glycol, wax and its mixture.
Compound with formula (I) be expected with alkylating agent, AI, antibody, antimetabolite, anti-have silk
Disintegrating agent, antiproliferative, antivirotic, aurora kinase inhibitors, apoptosis accelerator（Such as Bcl-xL, Bcl-w and Bfl-1）Suppression
Preparation, death receptor pathway * activator, Bcr-Abl kinase inhibitors, BiTE（Bi-Specific T cell Engager）It is anti-
Body, antibody drug conjugate, BRM, cell cycle protein dependent kinase inhibitor, cell cycle inhibitor,
Cyclooxygenase-2 inhibitor, DVDs, leukemia viral oncogene homologue（ErbB2）Acceptor inhibitor, growth factor receptor inhibitors,
The inhibitor of heat shock protein (HSP) -90, histon deacetylase (HDAC) (HDAC) inhibitor, hormone therapy medicine, immune substance, apoptosis
Albumen（IAPs）The inhibitor of inhibitor, intercalation antibiotic, kinase inhibitor, driving protein inhibitor, Jak2 inhibitor, thunder handkerchief
The mammalian target of mycin inhibitor, microRNA ' s, extracellular signal-regulated kinase inhibitor, the multivalence knot of mitogen activation
Hop protein, NSAIDs (NSAIDs), poly- ADP (adenosine diphosphate (ADP))-ribose polymerase (PARP) inhibitor, platinum chemotherapeutic
Thing, polo- samples kinases (Plk) inhibitor, PI-3 kinase (PI3K) inhibitor, proteasome inhibitor, purine analogue,
Pyrimidine analogue, receptor tyrosine kinase inhibitors, biostearin/deltoids, plant alkaloid, small inhibitory RNA
（siRNAs）, topoisomerase enzyme inhibitor, ubiquitinbond enzyme inhibitor etc. be used together and with one or more these reagent
It is useful when being used in combination.
BiTE antibody is the bispecific antibody by guiding T- cell challenges cancer cells in combination with two cells.T-
Cell then attacks target cancer cells.The example of BiTE antibody includes adecatumumab（Micromet MT201）、
Blinatumomab (Micromet MT103) etc..Without being bound by theory, but T- cells trigger target cancer cells apoptosis mechanism it
One is by lysis grain fraction（Including perforin and granzyme B）Exocytosis.
SiRNAs is the molecule with endogenous RNA bases or chemical modification nucleotides.This is modified and does not eliminate cytoactive,
But give the stability of raising and/or the cellular potency of raising.The example of chemical modification includes D2EHDTPA class, 2'- deoxidations
Nucleotides, containing 2'-OCH3Ribonucleotide, 2'-F- ribonucleotides, 2'- methoxyethyl ribonucleosides acid, its combination
Deng.SiRNA can have different length（Such as 10-200 bps）And structure（For example hairpin structure, mono-/bis-chain, bulge, breach/
Gap, mismatch）And process to provide active gene silence in cell.Double-strand siRNA（dsRNA）Can be in each chain（Blunt end）Or
Asymmetric end（Jag）The upper nucleotides with equal number.The jag of 1-2 nucleotides may be present in adopted and/or anti-
On adopted chain, and it is present on 5'- the and/or 3'- ends of given chain.
Multivalent binding proteins are the associated proteins comprising two or more antigen binding sites.Multivalent binding proteins are by work
Cheng Huawei has three or more antigen binding sites and not usually naturally occurring antibody." polyspecific is combined term
Albumen " refers to the associated proteins that can combine two or more related or uncorrelated targets.Double variable domains（DVD）Associated proteins are bags
Tetravalence or multivalent binding proteins containing two or more antigen binding sites.Such DVDs can be monospecific（I.e.
An antigen can be combined）Or polyspecific（Two or more antigens can be combined）.Comprising two heavy chain DVD polypeptides and two
The DVD associated proteins of individual light chain DVD polypeptides are referred to as DVD Ig's.Each half of DVD Ig includes heavy chain DVD polypeptides, light chain
DVD polypeptides and two antigen binding sites.Each binding site contains a heavy chain variable domain and a light-chain variable domain, each
Antigen binding site has 6 CDR of total to participate in antigen binding.
Alkylating agent include hemel, AMD-473, AP-5280, apaziquone, bendamustine,
Brostallicin, busulfan, carboquone, BCNU (BCNU), Chlorambucil, CLORETAZINE®
（Laromustine, VNP 40101M）, endoxan, dacarbazine（decarbazine）, estramustine, Fotemustine, Portugal's phosphorus
Acid amides, ifosfamide, KW-2170, lomustine（CCNU）, Mafosfamide, melphalan, dibromannitol, mitolactol,
Nimustine, mustargen N- oxides, Ranimustine, Temozolomide, thiotepa, TREANDA®（Bendamustine）, NSC-39069,
Rofosfamide etc..
AI includes endothelium-specific receptor EGFR-TK（Tie-2）Inhibitor, EGF
Acceptor（EGFR）Inhibitor, the acceptor of insulin-like growth factor -2（IGFR-2）Inhibitor, MMP-2（MMP-2）Suppression
Preparation, Matrix Metalloproteinase-9（MMP-9）Inhibitor, platelet-derived growth factor receptor（PDGFR）Inhibitor, blood platelet are anti-
Answer albumen analog, vascular endothelial growth factor receptor EGFR-TK（VEGFR）Inhibitor etc..
Antimetabolite includes ALIMTA®（Pemetrexed disodium, LY231514, MTA）, 5-azacitidine, XELODA®
（Capecitabine）, Carmofur, LEUSTAT®（Cladribine）, clofarabine, cytarabine, cytarabine octadecyl phosphoric acid
Salt, cytarabin, Decitabine, Deferoxamine, doxifluridine, Eflornithine, EICAR（5- acetenyl -1- β -
D-RIBOSE base imidazoles -4- formamides）, enocitabine, ethnylcytidine, fludarabine, individually or and Calcium Folinate-SF
The united 5 FU 5 fluorouracil of folic acid, GEMZAR®（Gemcitabine）, hydroxycarbamide, ALKERAN®（Melphalan）, purinethol, 6- mercaptos
Base purine riboside, methotrexate (MTX), mycophenolic acid, nelarabine, nolatrexed（nolatrexed）, octadecyl phosphate
（ocfosfate）, pelitrexol, Pentostatin, Raltitrexed, Ribavirin, triapine, Trimetrexate, S-1, thiazole
Furan woods, Tegafur, TS-1, arabinosy ladenosine, UFT etc..
Antivirotic includes Ritonavir, hydroxychloroquine etc..
Aurora kinase inhibitors include ABT-348, AZD-1152, MLN-8054, VX-680, the suppression of aurora A- specificity kinases
Preparation, aurora B- specificity kinases inhibitor and pan- aurora kinase inhibitors etc..
Bcl-2 protein inhibitors include AT-101（(-) gossypol）、GENASENSE®（G3139 or oblimersen
（oblimersen）（Bcl-2- targets ASON））, IPI-194, IPI-565, N- (4- (4- ((4'- chlorine (and 1,1'- join
Benzene) -2- bases) methyl) piperazine -1- bases) benzoyl) -4- (((1R) -3- (dimethylamino) -1- ((phenylsulfartyl) methyl)
Propyl group) amino) -3- nitrobenzene sulfonamides)（ABT-737）, N- (4- (4- ((2- (4- chlorphenyls) -5,5- dimethyl -1- hexamethylenes -
1- alkene -1- bases) methyl) piperazine -1- bases) benzoyl) -4- (((1R) -3- (morpholine -4- bases) -1- ((phenylsulfartyl) methyl)
Propyl group) amino) -3- ((trifluoromethyl) sulfonyl) benzsulfamide（ABT-263）、GX-070（obatoclax）Deng.
Bcr-Abl kinase inhibitors include DASATINIB®（BMS-354825）、GLEEVEC®（Imatinib）Deng.
CDK inhibitor include AZD-5438, BMI-1040, BMS-032, BMS-387, CVT-2584, flavopyridol,
GPC-286199、MCS-5A、PD0332991、PHA-690509、seliciclib（CYC-202、R-roscovitine）、ZK-
304709 etc..
Cox 2 inhibitor includes ABT-963, ARCOXIA®（Etoricoxib）、BEXTRA®（Valdecoxib）、
BMS347070、CELEBREX®（Celecoxib）、COX-189（Lumiracoxib）、CT-3、DERAMAXX®（SC 59046）、JTE-
522nd, 4- methyl -2- (3,4- 3,5-dimethylphenyls) -1- (4- aminosulfonylphenyl -1H- pyrroles), MK-663（Etoricoxib）、NS-
398th, SC 69124, RS-57067, SC-58125, SD-8381, SVT-2016, S-2474, T-614, VIOXX®（Rofecoxib）
Deng.
EGFR inhibitor includes ABX-EGF, anti-EGFR immunoliposome, EGF- vaccines, EMD-7200, ERBITUX®（West
Appropriate former times monoclonal antibody）, HR3, IgA antibody, IRESSA®（Gefitinib）、TARCEVA®（Erlotinib or OSI-774）、TP-38、
EGFR fusion proteins, TYKERB®（Lapatinib）Deng.
ErbB2 acceptor inhibitors include CP-724-714, CI-1033（Canertinib）、HERCEPTIN®（Trastuzumab）、
TYKERB®（Lapatinib）、OMNITARG®（2C4, petuzumab）、TAK-165、GW-572016（ionafarnib）、GW-
282974、EKB-569、PI-166、dHER2（HER2 vaccines）、APC-8024（HER-2 vaccines）, anti-HER/2neu bispecifics
Antibody, B7.her2IgG3, AS HER2 trifunctionals bispecific antibody, mAB AR-209, mAB 2B-1 etc..
Histon deacetylase (HDAC) inhibitor includes depsipeptide, LAQ-824, MS-275, trapoxin, Vorinostat
（SAHA）, TSA, valproic acid etc..
HSP-90 inhibitor include 17-AAG-nab, 17-AAG, CNF-101, CNF-1010, CNF-2024,17-DMAG,
Geldanamycin, IPI-504, KOS-953, MYCOGRAB®（People's recombinant antibodies of HSP-90）、NCS-683664、PU24FCl、
PU-3, radicicol, SNX-2112, STA-9090 VER49009 etc..
The inhibitor of inhibitor of apoptosis protein includes HGS1029, GDC-0145, GDC-0152, LCL-161, LBW-242
Deng.
Antibody drug conjugate includes anti-CD22-MC-MMAF, anti-CD22-MC-MMAE, anti-CD22-MCC-DM1, CR-
011-vcMMAE, PSMA-ADC, MEDI-547, SGN-19Am SGN-35, SGN-75 etc..
Death receptor pathway * activator includes TRAIL, targeting TRAIL or death receptor（Such as DR4 and DR5）Antibody or
Other reagents, such as Apomab, his native pearl of west（conatumumab）、ETR2-ST01、GDC0145、（Carry out husky wooden monoclonal antibody）、HGS-
1029th, LBY-135, PRO-1762 and trastuzumab.
Driving protein inhibitor includes Eg5 inhibitor, such as AZD4877, ARRY-520；CENPE inhibitor, such as
GSK923295A etc..
JAK-2 inhibitor includes CEP-701（lesaurtinib）, XL019 and INCB018424 etc..
Mek inhibitor is including ARRY-142886, ARRY-438162 PD-325901, PD-98059 etc..
MTOR inhibitors include AP-23573, CCI-779, everolimus, RAD-001, rapamycin, CCI-779,
ATP- competitiveness TORC1/TORC2 inhibitor, including PI-103, PP242, PP30, Torin 1 etc..
NSAIDs includes AMIGESIC®（Salsalate）、DOLOBID®（Diflunisal）、MOTRIN®（Bu Luo
It is fragrant）、ORUDIS®（Ketoprofen）、RELAFEN®（Nabumetone）、FELDENE®（Piroxicam）, Ibuprofen cream,
ALEVE®（Naproxen）And NAPROSYN®（Naproxen）、VOLTAREN®（Diclofenac）、INDOCIN®（Indomethacin）、
CLINORIL®（Sulindac）、TOLECTIN®（Tolmetin）、LODINE®（Etodolac）、TORADOL®（Ketorolac）、DAYPRO®（Olsapozine）Deng.
PDGFR inhibitor is including C-451, CP-673, CP-868596 etc..
Platinum chemotherapeutics includes cis-platinum, ELOXATIN®（Oxaliplatin）, eptalatin, lobaplatin, Nedaplatin, PARAPLATIN®
（Carboplatin）, Satraplatin, JM473 etc..
Polo-like kinase inhibitor is including BI-2536 etc..
PI-3 kinase（PI3K）Inhibitor includes wortmannin, LY294002, XL-147, CAL-120, ONC-
21st, AEZS-127, ETP-45658, PX-866, GDC-0941, BGT226, BEZ235, XL765 etc..
Thrombospondin analog is including ABT-510, ABT-567, ABT-898, TSP-1 etc..
VEGFR inhibitor includes AVASTIN®（Bevacizumab）、ABT-869、AEE-788、ANGIOZYME™（Suppress blood
The ribozyme of pipe generation（Ribozyme Pharmaceuticals（Boulder, CO.）And Chiron, (Emeryville,
CA））, Axitinib（AG-13736）、AZD-2171、CP-547,632、IM-862、MACUGEN（pegaptamib）、
NEXAVAR®（Sorafenib, BAY43-9006）, pazopanib（GW-786034）, PTK787（PTK-787, ZK-
222584）、SUTENT®（Sutent, SU-11248）、VEGF trap、ZACTIMA™（ZD6474, ZD-6474）Deng.
Antibiotic include intercalation antibiotic Aclarubicin, actinomycin D, Amrubicin, anthracycline, adriamycin,
BLENOXANE®（Bleomycin）, daunorubicin, CAELYX®Or MYOCET®（Liposomal doxorubicin）, Elsamitrucin,
epirbucin、glarbuicin、ZAVEDOS®（Idarubicin）, mitomycin C, Nemorubicin, neoearcinostain, Pei Luo
Mycin, THP, butterfly mycin, stimalamer, streptozotocin, VALSTAR®（Valrubicin）, Zinostatin etc..
Topoisomerase enzyme inhibitor include Aclarubicin, 9-aminocamptothecin, Amonafide, amsacrine,
Becatecarin, Belotecan, BN-80915, CAMPTOSAR®（CPT-11）, camptothecine, CARDIOXANE®
（ADR-529）, fluorine replace health（diflomotecan）、edotecarin、ELLENCE®Or PHARMORUBICIN®（The soft ratio of table
Star）, Etoposide, Exatecan, 10-hydroxycamptothecine, gefitinib, Lurtotecan, mitoxantrone, Rubitecan
（orathecin）, pirarbucin, pixantrone, Rubitecan, Sobuzoxane, SN-38, tafluposide, TPT etc..
Antibody includes AVASTIN®（Bevacizumab）, CD40- specific antibodies, chTNT-1/B, promise monoclonal antibody, ERBITUX®（Cetuximab）、HUMAX-CD4®（Prick wooden monoclonal antibody（zanolimumab））, IGF1R- specific antibodies, lintuzumab,
PANOREX®（Edrecolomab）、RENCAREX®（WX G250）、RITUXAN®（Rituximab）、ticilimumab、
Trastuzimab, CD20 Antibody types I and II etc..
Hormone therapy medicine includes ARIMIDEX®（Anastrozole）、AROMASIN®（Exemestane）, arzoxifene,
CASODEX®（Bicalutamide）、CETROTIDE®（Cetrorelix）, Ac-D-2Nal-D-4Cpa-D-3Pal-Ser-4Aph(Hor)-D-4Aph(Cbm)-Leu-Lys(iPr)-Pro-D-Ala-NH2, Deslorelin, DESOPAN®（Trilostane）、
Dexamethasone, DROGENIL®（Drogenil）、EVISTA®（Raloxifene）、AFEMA™（Fadrozole）、FARESTON®（Tuo Rui
Meter Fen）、FASLODEX®（Fulvestrant）、FEMARA®（Letrozole）, Formestane, glucocorticoid, HECTOROL®（Degree bone
Change alcohol）、RENAGEL®（2-Propen-1-amine polymer with(chloromethyl)oxirane carbonate）, lasofoxifene, leuprorelin acetate, MEGACE®（Megestrol acetate）、MIFEPREX®（Mifepristone）、NILANDRON™（Nilutamide）、NOLVADEX®（TAMOXIFEN CITRATE）、PLENAXIS™（A Barui
Gram）, prednisone, PROPECIA®（Finasteride）、rilostane、SUPREFACT®（Buserelin）、TRELSTAR®（Promote yellow
Voxel releasing hormone（LHRH））、VANTAS®（Histrelin implant）、VETORYL®（Trilostane or modrastane）、
ZOLADEX®（Fosrelin, Goserelin）Deng.
Deltoids and biostearin include seocalcitol（EB1089、CB1093）、lexacalcitrol
（KH1060）, HPR（fenretinide）、PANRETIN®（aliretinoin）、ATRAGEN®（Liposome Wei Jia
Acid）、TARGRETIN®（Bexarotene）, LGD-1550 etc..
PARP inhibitor includes ABT-888（veliparib）, olaparib, KU-59436, AZD-2281, AG-
014699th, BSI-201, BGP-15, INO-1001, ONO-2231 etc..
Plant alkaloid includes but is not limited to vincristine, vincaleukoblastinum, eldisine, vinorelbine etc..
Proteasome inhibitor includes VELCADE®（Bortezomib）, MG132, NPI-0052, PR-171 etc..
The example of immune substance includes interferon and other immunopotentiators.Interferon include interferon-' alpha ', Intederon Alpha-2a,
Interferon Alpha-2b, interferon beta, interferon gamma -1a, ACTIMMUNE®（Gamma interferon 1-b）Or interferon gamma-n1, its combination etc..
Other reagents include ALFAFERONE®（IFN-α）、BAM-002（Oxidized form of glutathione）、BEROMUN®（Tasonermin）、
BEXXAR®（Tositumomab）、CAMPATH®（Alemtuzumab）、CTLA4（Cytotoxic lymphocite antigen 4）, dacarbazine,
Denileukin, epratuzumab, GRANOCYTE（Lenograstim）, lentinan, leucocyte IFN-α, imiquimod,
MDX-010（Anti- CTLA-4）, melanoma vaccines, mitumomab, Molgramostim, MYLOTARG（WAY-CMA 676 Austria azoles rice
Star）、NEUPOGEN®（Filgrastim）、OncoVAC-CL、OVAREX®（oregovomab）、pemtumomab（Y-muHMFG1）、
PROVENGE®（sipuleucel-T）, sargaramostim, schizophyllum abamectin（sizofilan）, Teceleukin, THERACYS®（BCG vaccine）, ubenimex, VIRULIZIN®（Immunization therapy, Lorus Pharmaceuticals）、Z-100（Specific
Substance of Maruyama（SSM））、WF-10（Tetrachlorodecaoxide（TCDO））、PROLEUKIN®（A Di
Interleukin）、ZADAXIN®（Thymalfasin）、ZENAPAX®（Zenapax）、ZEVALIN®（90Y- ibritumomab tiuxetans）Deng.
BRM is the defense mechanism or biological respinse for changing live organism, such as histiocytic survival, life
It is long or break up so that they have the reagent of antitumor activity, and including coriolan, lentinan, Sizofiran, molten chain bacterium PF-
3512676（CpG-8954）, ubenimex etc..
Pyrimidine analogue includes cytarabine（Ara C or Arabinoside C）, cytarabin, deoxidation fluorine urine
Glycosides, FLUDARA®（Fludarabine）、5-FU（5 FU 5 fluorouracil）, floxuridine, GEMZAR®（Gemcitabine）、TOMUDEX®
（ratitrexed）、TROXATYL™（Triacetyl uridine troxacitabine）Deng.
Purine analogue includes LANVIS®（Thioguanine）And PURI-NETHOL®（Purinethol）.
Antimitotic agent includes batabulin, Epothilone D（KOS-862）, N- (2- ((4- hydroxy phenyls) amino)
Pyridin-3-yl) -4- methoxybenzenesulphoismides, Ipsapirone（BMS 247550）, taxol, TAXOTERE®（Taxotere
Alcohol）、PNU100940（109881）, handkerchief soil a dragon（patupilone）、XRP-9881（larotaxel）, vinflunine, ZK-
EPO（Synthesis Epothilones）Deng.
Ubiquitinbond enzyme inhibitor includes MDM2 inhibitor such as nutlins, NEDD8 inhibitor such as MLN4924.
Compound of the invention also acts as the radiosensitizer of the effect of enhancing radiotherapy.The example bag of radiotherapy
Include external beam radiation therapy, teletherapy, brachytherapy and sealing, unsealed source radiotherapy etc..
In addition, the compound with formula (I) can be with other following chemotherapeutic agents, such as ABRAXANE（ABI-
007）、ABT-100（Farnesyl transferase inhibitor）、ADVEXIN®（Ad5CMV-p53 vaccines）、ALTOCOR®Or MEVACOR®
（Lovastatin）、AMPLIGEN®（poly I:Poly C12U, synthesis RNA）、APTOSYN®（Exisulind）、AREDIA®（Handkerchief
Rice phosphonic acids）, arglabin, L-ASP, atamestane（1- methyl -3,17- diketone-androstane -1,4- diene）、AVAGE®
（Tazarotene）、AVE-8062（Combreastatin derivatives）、BEC2（Mitumomab）, cachectin or cachexin
（TNF）、canvaxin（Vaccine）、CEAVAC®（Cancer vaccine）、CELEUK®（Celmoleukin）、CEPLENE®
（Histamine dihydrochloric acid）、CERVARIX®（Human-papilloma Vaccine）、CHOP®（C: CYTOXAN®（Endoxan）；H:Ah
Mycin（hydroxydoxorubicin）；O:Vincristine（ONCOVIN®）；P:Prednisone）、CYPAT™（Acetic acid ring third
Progesterone）、combrestatin A4P、DAB(389)EGF（It is fused on hEGF via His-Ala connexons
The catalysis of diphtheria toxin and translocation domain）Or TransMID-107R（Diphtheria toxin）, dacarbazine, actinomycin D, 5,
6- dimethyl xanthone -4- acetic acid（DMXAA）、eniluracil、EVIZON™（Lactic acid squalamine）、DIMERICINE®（T4N5
Liposome emulsion）, circle suberite lactone（discodermolide）、DX-8951f（Exatecan mesylate）、
enzastaurin、EPO906（epithilone B）、GARDASIL®（Tetravalence human papilloma virus（6th, 11,16,18 type）Weight
Group vaccine）、GASTRIMMUNE®、GENASENSE®、GMK（Gangliosides combined vaccine）、GVAX®（Vaccine for prostate cancer）、
Halofuginone hydrobromide, histerelin, hydroxycarbamide, ibandronic acid, IGN-101, IL-13-PE38, IL-13-PE38QQR
（cintredekin besudotox）, IL-13- PEs, interferon-' alpha ', interferon-γ, JUNOVAN or
MEPACT™（Rice lumbering peptide）, Luo Nafani（lonafarnib）, 5,10- methylene tetrahydrofolates, Miltefosine（Cetyl
Phosphocholine）、NEOVASTAT®（AE-941）、NEUTREXIN®（Glucuronic acid Trimetrexate）、NIPENT®（Pentostatin）、
ONCONASE®（Ribalgilase）、ONCOPHAGE®（Melanoma vaccines are treated）、ONCOVAX®（IL-2 vaccines）、
ORATHECIN™（Rubitecan）、OSIDEM®（Antibody basal cell's medicine）、OVAREX®MAb（Mouse monoclonal antibody）, Japanese yew
Alcohol, PANDIMEX（Comprising 20 (S) protopanoxadiols（aPPD）With 20 (S) Protopanaxatriols（aPPT）From ginseng
Aglycone saponin）, Victibix, PANVAC®-VF（Cancer vaccine in research）, Pegaspargase, PEG interferon As, benzene it is appropriate
Supreme Being's that（phenoxodiol）, procarbazine, rebimastat, REMOVAB®（catumaxomab）、REVLIMID®（Carry out that degree
Amine）、RSR13（Efaproxiral）、SOMATULINE®LA（Lanreotide）、SORIATANE®（Acitretin）, staurosporine（Streptomycete
Staurospore）、talabostat（PT100）、TARGRETIN®（Bexarotene）、TAXOPREXIN®（DHA- taxols）、
TELCYTA®（Canfosfamide, TLK286）、temilifene、TEMODAR®（Temozolomide）, tesmilifene, Sha Lidu
Amine, THERATOPE®（STn-KLH）、thymitaq（2- amino -3,4- dihydro -6- methyl -4- oxos -5- (4- pyridine radicals sulphur
Generation) quinazoline dihydrochloride）、TNFERADE™（Adenovirus vector:The DNA vector of the gene containing tumor necrosis factor-alpha）、
TRACLEER®Or ZAVESCA®（Bosentan）, vitamin A acid（RA）, Tet, TRISENOX®（Arsenic trioxide）、
VIRULIZIN®、ukrain（Alcaloid-derivatives from greater celandine plant）、vitaxin（The anti-antibody of α v β 3）、XCYTRIN®（Motexafin gadolinium）、XINLAY™（Atrasentan）、XYOTAX™（paclitaxel poliglumex）、YONDELIS®（It is bent
Shellfish is for fixed）、ZD-6126、ZINECARD®（Dexrazoxane）、ZOMETA®（Zoledronic acid（zolendronic acid））, help it is soft
Compare magnitude.
Data
The compound with formula (I) is carried out using time-resolved fluorescence Resonance energy transfer (TR-FRET) binding analysis method
As the measure of the effectiveness of the inhibitor of the conjugate and NAMPT of NAMPT.
Time-resolved fluorescence Resonance energy transfer (TR-FRET) binding analysis method of NAMPT
By test compound serial dilution (usual 11 half-log) to 50X final concentrations in pure DMSO, then use and divide
Analysis buffer solution (50 mM HEPES (NaOH), pH 7.5,100 mM NaCl, 10 mM MgCl2, 1 mM DTT, 1%
Glycerine) it is diluted to 3X and 6% DMSO.6 L are transferred to the low volume plate in 384 holes (Owens Corning #3673).Thereto
Add the 1.5X solution containing enzyme, probe and antibody of 12 L.Ultimate density in 18 L reactions is 1X analysis buffers, 2%
DMSO, 6.8 nM NAMPT (people, recombinant, C- terminal His-tags), 200 nM probes (are effectively conjugated to
Niacinamide-the competitive inhibitor of Oregon Green 488) and anti-His antibody (the Invitrogen # of 1 nM Tb-
PV5895).Make reaction balance at room temperature 3 hours, then reading (the Perkin on Envision multiple labeling plate readers
Elmer；Ex=337 nm, Em=520 and 495 nm).By time resolution FRET ratios (Em520/Em495) relative to right
According to thing normalization, curve is drawn according to compound concentration and four parameter logistics this base of a fruit equation models is used to determine IC50s.
Using time-resolved fluorescence Resonance energy transfer (TR-FRET) binding analysis method of the NAMPT of PRPP
Compound treatment and data processing are identical with the analysis in the absence of substrate（As described above）.Final concentration of 1X analyses
Buffer solution, 2% DMSO, 2 nM NAMPT, 2 nM probes, anti-His antibody (the Invitrogen # of 1 nM Tb-
), PV5895 200 M PRPP and 2.5 mM ATP.Before measuring by reaction balance 16 hours so that test compound occurs
Potential enzyme modification.
Table 1 shows that the compound feature with Formulas I suppresses the effectiveness of NAMPT.
Table 1
Nd=no data.
NAMPT cell proliferating determinings
PC3 cells are seeded in 96 holes in the RPMI media of 90 L containing 10% heat inactivation FBS with 500 cells/wells
In blackboard (Corning #3904) and at 37 DEG C and 5% CO2Lower overnight incubation is so that cell is adhered to hole.Ensuing one day,
By test compound serial dilution to 1000X final concentrations in pure DMSO, then with RPMI mediums to 10X and 1%
DMSO.Then the 10X compounds of 10 L are transferred in the hole containing cell to produce 10 times of dilutions（The x of 10 M to 1 10-5M）
Dose response.At 37 DEG C and 5% CO2It is lower by cell culture 5 days, then use Cell Titer Glo reagents (Promega #
G7571 cell viability) is determined.Calculate percentage inhibiting value and be fitted to S-shaped dose response using Assay Explorer softwares
Curve is determining IC50.Suppress whether to be because NAMPT suppresses, also in 0.3 mM niacinamide monokaryon glycosides to evaluate cell viability
Proliferation assay is carried out in the presence of acid.
Table 2 shows the result of cell proliferating determining.
Table 2
Nd=no data.
The compound for suppressing NAMPT can be used to treat the disease for being directed to NF-KB activation.Such method can be used to treat
Various diseases, including inflammation and tissue repair obstacle；Particularly rheumatoid arthritis, inflammatory bowel disease, asthma and COPD are (slow
Property obstructive lung disease), osteoarthritis, osteoporosis and fibrotic conditions；Skin disease, including psoriasis, allergic dermatitis
With the skin injury of induced by ultraviolet irradiation；Autoimmune disease, including systemic lupus erythematosus, multiple sclerosis, psoriasis are closed
Section is scorching, mandatory rachitis, organizes and organ rejection, Alzheimer disease, apoplexy, atherosclerosis, ISR, glycosuria
Disease, glomerulonephritis, cancer, particularly wherein described cancer is selected from breast cancer, prostate cancer, lung cancer, colon cancer, cervix
Cancer, oophoroma, cutaneum carcinoma, CNS cancers, carcinoma of urinary bladder, cancer of pancreas, leukaemia, lymthoma or Hodgkin's disease, cachexia, with infection
The inflammation related to some viral infections, including Immune Deficiency Syndrome (AIDS), adult respiratory distress syndrome's synthesis
Disease, and ataxia-telangiectasia.
It is related to NAMPT in having recorded treatment of cancer in WO 97/48696.Immune suppression has been recorded in WO 97/48397
It is related to NAMPT in system.Recorded in WO 2003/80054 and be related to NAMPT in the treatment of the disease of angiogenesis is related to.
It is related to NAMPT in the treatment that rheumatoid arthritis and infectious shock have been recorded in WO 2008/025857.In WO 2009/
Recorded in 109610 and be related to NAMPT in the prevention and treatment of local anemia.
Cancer includes but is not limited to neoplastic hematologic disorder and solid tumor types such as acoustic neurinoma, acute leukemia, acute into lymph
Chronic myeloid leukemia, acute myelogenous leukemia (monocarpotic cellularity, myeloblastic, gland cancer, angiosarcoma, astrocytoma, marrow
Monocarpotic cellularity and promyelocytic leukemic cell), acute t- chronic myeloid leukemias, basal-cell carcinoma, cholangiocarcinoma, carcinoma of urinary bladder, the cancer of the brain, mammary gland
Cancer (including estrogen receptor positive breast cancer), bronchiolar carcinoma, Burkitt lymphoma, cervical carcinoma, chondrosarcoma, spinal cord knurl, suede
Trichilemma cancer, chronic leukemia, chronic lymphocytic leukemia, chronic myelocytic (granulocyte) leukaemia, the white blood of chronic myelognous
Disease, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, bad propagation change (depauperation and metaplasia), embryonal carcinoma, son
Endometrial carcinoma, endotheliosarcoma, ependymoma, epithelioma, erythroleukemia, the cancer of the esophagus, estrogen receptor positive breast cancer, primary
Thrombocythemia, Ewing's tumor, fibrosarcoma, stomach cancer, reproduction cell carcinoma of testis, gestational trophoblastic disease, glioblastoma,
The insensitive prostate cancer of head and neck cancer, heavy chain disease, hemangioblastoma, liver cancer, hepatocellular carcinoma, hormone, leiomyosarcoma, fat
Sarcoma, lung cancer (including ED-SCLC and non-small cell lung cancer), lymphangioendothelial sarcoma, lymphangioendothelial sarcoma, lymphoblast
Leukaemia, lymthoma (lymthoma, including Diffuse Large B-Cell Lymphoma, follicular lymphoma, hodgkin's lymphoma and Fei Hejie
Golden lymthoma), bladder, mammary gland, colon, lung, ovary, pancreas, prostate, the malignant tumour in skin and uterus and hyperplasia barrier
Hinder, T cell or B cell source lymphoid malignancies, leukaemia, cephaloma, medulloblastoma, melanoma, meninx
Knurl, celiothelioma, Huppert's disease, myelomatosis, myeloma, myxosarcoma, neuroblastoma, mesoglia
Knurl, carcinoma of mouth, osteogenic sarcoma, oophoroma, cancer of pancreas, papillary gland cancer, papillary carcinoma, periphery T cell lymph cancer, pineal body
Knurl, erythremia, prostate cancer (including insensitive (intractable) prostate cancer of hormone), the carcinoma of the rectum, clear-cell carcinoma, into view
Theca cell knurl, rhabdomyosarcoma, sarcoma, carcinoma of sebaceous glands, seminoma, cutaneum carcinoma, ED-SCLC, solid tumor (cancer and meat
Knurl), stomach cancer, squamous cell carcinoma, synovialoma, syringocarcinoma, carcinoma of testis (including reproduction cell carcinoma of testis), thyroid cancer, Walden
Si Telun macroglobulinemias, testicular tumor, the cancer of the uterus, wilms' tumor etc..
Scheme and experiment
Below abbreviation has specified implication.ADDP represents 1,1'- (azo dicarbapentaborane) two piperidines；AD- mixes-β tables
Show (DHQD)2PHAL、K3Fe(CN)6、K2CO3And K2SO4Mixture；9-BBN represents 9- borabi cyclos (3.3.1) nonane；Boc
Represent tert-butoxycarbonyl；(DHQD)2PHAL represents hydroquinidine 1,4- phthalazines diyl diethyl ether；DBU represents 1,8- phenodiazines
Carbon -7- the alkene of miscellaneous two ring [5.4.0] 11；DIBAL represents diisobutyl aluminium hydride；DIEA represents diisopropyl ethyl amine；DMAP
Represent N, N- dimethyl aminopyridines；DMF represents N,N-dimethylformamide；Dmpe represents double (dimethyl phosphino-) second of 1,2-
Alkane；DMSO represents dimethyl sulfoxide (DMSO)；Dppb represents double (the diphenylphosphino)-butane of 1,4-；Dppe represents the double (diphenyl of 1,2-
Phosphino-) ethane；Dppf represents double (diphenylphosphino) ferrocene of 1,1'-；Dppm represents double (diphenylphosphino) methane of 1,1-；
EDACHCl represents 1- (3- dimethylaminopropyls) -3- ethyl-carbodiimide hydrochlorides；Fmoc represents fluorenyl methoxy carbonyl
Base；HATU represents O- (7- azepine benzos triazol-1-yl)-N, N'N'N'- tetramethylurea hexafluorophosphates；HMPA represents pregnancy
Base phosphamide；IPA represents isopropanol；MP-BH3Represent macropore triethyl methyl polystyrene cyano group ammonium borohydride；TEA represents three
Ethamine；TFA represents trifluoroacetic acid；THF represents tetrahydrofuran；NCS represents N-chloro-succinimide；NMM represents N-methylmorpholine；
NMP represents N- crassitudes；PPh3Represent triphenylphosphine.
It is considered as most useful and step of the invention that is being readily appreciated that and general that following scheme is demonstrated to provide those
Description in terms of thought.Compound of the invention can be prepared by synthesizing chemical method, and embodiment shows herein.It is intended to
The order for being interpreted as method and step can be varied as, and can be replaced with reagent, solvent and reaction condition on demand and specifically carried
And those, and can on demand by unstable radical protection and deprotection.
Scheme
Scheme 1
As shown in scheme 1, formula (1) compound（Wherein X1、X2And R1As described in formula (I), n is 1 or 2, m are 1 or 2, works as n
For 1 or 2 and m be 1 when X be CH, and when n be 2 and m be 2 when X be N or CH）Can it is double in carbonic acid (2,5- dioxo pyrrolidins-
1- yls) ester and alkali（Such as but not limited to diisopropyl ethyl amine）In the presence of with formula (2) compound（Wherein R2It is as described herein）
React to provide the compound of formula (3).The reaction is generally carried out in solvent is such as, but not limited to acetonitrile at room temperature.
Scheme 2
4- (4- aminophenyls) piperidines -1- t-butyl formates can be with formula (1) compound（Wherein X1、X2And R1Such as formula (I)
Described, n is 1 or 2, m are 1 or 2, when n is that X is CH when 1 or 2 and m is 1, and when n is that X is N or CH when 2 and m is 2）In carbonic acid
Double (2,5- dioxo pyrrolidin -1- bases) esters and alkali（Such as but not limited to diisopropyl ethyl amine）In the presence of react to provide formula
(4) compound.The reaction is generally carried out in solvent is such as, but not limited to acetonitrile at room temperature.Can by solvent for example but
It is not limited to be such as, but not limited to trifluoroacetic acid processing formula (4) compound come formula (5) compound using acid in dichloromethane.Formula
(7) compound（It is the representative of formula (I) compound）Can be such as, but not limited in the presence of diisopropyl ethyl amine by alkali
Make formula (5) compound and formula (6) compound（Wherein R10It is as described herein）React to prepare.The reaction may involve the use of carboxyl work
Agent is such as, but not limited to N- (3- dimethylaminopropyls)-N'- ethyl-carbodiimide hydrochlorides, ester activator for example but does not limit
In I-hydroxybenzotriazole hydrate.The reaction generally at room temperature solvent be such as, but not limited to N,N-dimethylformamide,
Carried out in DMAC N,N' dimethyl acetamide or its mixture.Or, formula (5) compound can be with formula (8) compound（Wherein R10Such as this
It is literary described）React to provide formula (9) compound（It is the representative of formula (I) compound）.It is described to react generally in reducing agent for example
But it is not limited to be carried out in solvent such as but not limited to methyl alcohol in the presence of sodium triacetoxy borohydride and acetic acid and can be
Carried out at elevated temperature.
Scheme 3
As shown in Scheme 3,3- (4- amino-benzene oxygens) azetidine -1- t-butyl formates can be in carbonic acid double (2,5-
Dioxo pyrrolidin -1- bases) ester and alkali is such as, but not limited in the presence of diisopropyl ethyl amine and formula (1) compound（Wherein X1、
X2And R1As described in formula (I), n be 1 or 2, m be 1 or 2, when n be 1 or 2 and m be 1 when X be CH, when n be 2 and m be 2 when X be N or
CH）React to provide formula (10) compound.The reaction is generally carried out in solvent is such as, but not limited to acetonitrile at room temperature.Can be with
Made by being such as, but not limited to trifluoroacetic acid processing formula (10) compound with acid in solvent is such as, but not limited to dichloromethane
Standby formula (11) compound.Can be in the presence of alkali be such as, but not limited to diisopropyl ethyl amine by making formula (11) compound and formula
(6) compound（Wherein R10It is as described herein）Reaction carrys out formula (12) compound（It is the representative of formula (I) compound）.Should
Reaction may involve the use of carboxyl activator such as but not limited to N- (3- dimethylaminopropyls)-N'- ethyl carbodiimide hydrochlorides
Salt and ester activator are such as, but not limited to I-hydroxybenzotriazole hydrate.The reaction generally at room temperature in solvent for example but not
It is limited to be carried out in N,N-dimethylformamide, DMAC N,N' dimethyl acetamide or its mixture.
Embodiment
It is considered as most useful and step of the invention and concept that be readily appreciated that following examples are presented to provide those
The description of aspect.Use ACD/ChemSketch Ver. 12.5 (20 April 2011), Advanced Chemistry
Development Inc., Toronto, Ontario) or ChemDraw Ver. 9.0.7 (CambridgeSoft,
Cambridge, MA) each embodiment compound and intermediate are named.
Experiment
Embodiment 1
N- [4- ({ 1- [(2S) -2- methylbutyryls base] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides
Embodiment 1A
3- (4-nitrophenoxy) azetidine -1- t-butyl formates
By 3- hydroxy azetidine -1- t-butyl formates (4.0 g, 23.3 mmol), the fluoro- 4- nitrobenzene (6.1 of 1-
G, 43.0 mmol), potassium hydroxide aqueous solution (the 5.9 M solution of 35.5 ml, 209 mmol) and TBAB
(0.975 g, 3.0 mmol) mix and are stirred overnight at 40 DEG C.Reaction cooling, dilute with water are simultaneously extracted with ethyl acetate
Take three times.The organic matter that will merge is dried（Sodium sulphate）, filtering and concentrate.By the flash chromatography eluting residue of positive with
Title compound is provided.
Embodiment 1B
3- (4- amino-benzene oxygens) azetidine -1- t-butyl formates
In 250 mL SS pressure bottles, by 3- (4-nitrophenoxy) azetidine -1- t-butyl formates (1g,
3.40 mmol) and tetrahydrofuran (20 ml) added to 5% palladium on carbon (wet, 0.200 g, 1.879 mmol) and 30
Psi and at room temperature by the mixture stir 1 hour.By the nylon membrane filtration mixture and filtrate is concentrated to provide title compound
Thing.
Embodiment 1C
3- (4- (3- (pyridin-3-yl) azetidine -1- formamidos) phenoxy group) tertiary fourth of azetidine -1- formic acid
Ester
3- (4- amino-benzene oxygens) azetidine -1- t-butyl formates (1.17 g, 4.43 mmol) and carbonic acid is double
(2,5- dioxo pyrrolidin -1- bases) ester (1.134 g, 4.43 mmol) mix and in room temperature in acetonitrile (22.13 ml)
Lower stirring 1 hour.Add 3- (azetidine -3- bases) pyridine dihydrochloride (0.948 g, 4.65 mmol) and diisopropyl
Simultaneously be stirred overnight for reactant mixture by base ethylamine (3.09 ml, 17.71 mmol).Acetonitrile is removed simultaneously by rotary evaporation
Residue is dissolved in dichloromethane, and chromatographs to provide title compound with normal-phase chromatography method.
Embodiment 1D
N- (4- (azetidine -3- bases epoxide) phenyl) -3- (pyridin-3-yl) azetidine -1- formamides
To added in 20 mL bottles in dichloromethane (9.42 mL) 3- (4- (3- (pyridin-3-yl) azetidine-
1- formamidos) phenoxy group) azetidine -1- t-butyl formates (800 mg, 1.885 mmol).Add trifluoroacetic acid
(1.4 mL, 18.17 mmol) are simultaneously stirred at room temperature the reactant mixture 1.5 hours.Volatile matter is removed under reduced pressure to carry
For title compound.
Embodiment 1E
(S)-N- (4- (1- (2- methylbutyryls base) azetidine -3- bases epoxide) phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides
At room temperature by N- (4- (azetidine -3- bases epoxide) phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide (1 g, 1.805 mmol), (S) -2-Methyl Butyric Acid (0.221 g, 2.166 mmol) and N- (3- dimethylaminos
Base propyl group)-N'- ethyl-carbodiimide hydrochlorides (0.519 g, 2.71 mmol) are in dimethylformamide (9.03 mL)
Mixing.Addition I-hydroxybenzotriazole hydrate (0.415 g, 2.71 mmol) and diisopropyl ethyl amine (0.946 ml,
5.42 mmol) and the reactant mixture is stirred at room temperature overnight.Add water and dichloromethane and removed by pipette organic
Thing.Concentrate and reversed phase chromatography provides (S)-N- (4- (1- (2- methylbutyryls base) azetidine -3- bases epoxide) phenyl) -3-
(pyridin-3-yl) azetidine -1- formamides.
Table 1.
Following examples are substantially prepared as described in Example 1, are used with suitable alcohol, embodiment 1C in embodiment 1A
Replaced with suitable carboxylic acid in suitable amine and embodiment 1E.Some products pass through anti-phase by flash chromatography
HPLC methods purify other products.Therefore, some embodiments are separated into trifluoroacetate.
Embodiment 9
N- (4- { 1- [(2S) -2- methylbutyryls base] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides
Embodiment 9A
4- (4- nitrobenzophenones) -5,6- dihydropyridines -1 (2H)-t-butyl formate
In 350 mL seal pressure flasks, by the bromo- 4- nitrobenzene of 1- (4.00 g, 19.80 mmol), 4- (4,4,5,
5- tetramethyl -1,3,2- dioxaborolan alkane -2- bases) -5,6- dihydropyridines -1 (2H)-t-butyl formate (6.74 g,
21.78 mmol) and sodium carbonate (4.41 g, 41.6 mmol) in tetrahydrofuran (60 ml), water (30 ml) and methyl alcohol (10
Ml mixing in).The mixture is purged into circulation by three vacuum/nitrogens.Add [double (diphenylphosphino) ferrocene of 1,1'-]
Palladium chloride (II) dichloromethane (0.485 g, 0.594 mmol), under a nitrogen adds the reactant mixture at 70 DEG C
Heat is overnight.The reactant mixture is cooled down, each layer is diluted and separated with ethyl acetate and water.It is extracted with ethyl acetate water layer and concentrates
The organic layer of merging.Normal-phase chromatography method provides title compound.
Embodiment 9B
4- (4- aminophenyls) -5,6- dihydropyridines -1 (2H)-t-butyl formate
Title compound is prepared as described in embodiment 1B, with 4- (4- nitrobenzophenones) -5,6- dihydropyridines -1 (2H)-formic acid
The tert-butyl ester substitutes 3- (4-nitrophenoxy) azetidine -1- t-butyl formates.
Embodiment 9C
4- (4- (3- (pyridin-3-yl) azetidine -1- formamidos) phenyl) -5,6- dihydropyridines -1 (2H)-first
Tert-butyl acrylate
Title compound is prepared as described in embodiment 1C, with 4- (4- aminophenyls) -5,6- dihydropyridines -1 (2H)-formic acid
The tert-butyl ester substitutes 3- (4- amino-benzene oxygens) azetidine -1- t-butyl formates.
Embodiment 9D
3- (pyridin-3-yl)-N- (4- (1,2,3,6- tetrahydropyridine -4- bases) phenyl) azetidine -1- formamides
Title compound is prepared as described in embodiment 1D, with 4- (4- (3- (pyridin-3-yl) azetidine -1- formamides
Base) phenyl) piperidines -1- t-butyl formates replacement 3- (4- (3- (pyridin-3-yl) azetidine -1- formamidos) phenoxy group)
Azetidine -1- t-butyl formates.
Embodiment 9E
N- (4- { 1- [(2S) -2- methylbutyryls base] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides
Prepare title compound as described in embodiment 1E, with 3- (pyridin-3-yl)-N- (4- (1,2,3,6- tetrahydropyridine-
4- yls) phenyl) azetidine -1- formamides replacement N- (4- (azetidine -3- bases epoxide) phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides.
Table 2.
Following examples are substantially prepared as described in Example 9, are replaced with suitable carboxylic acid in embodiment 9E.By fast
Fast purification by chromatography some products, and pass through rp-hplc method and purify other products.Therefore, some embodiments are separated into trifluoro second
Hydrochlorate.
Embodiment 13
4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) methyl benzoate
By 3- (azetidine -3- bases) pyridine, double trifluoroacetic acids (75 mg, 0.207 mmol) and diisopropyl second
Base amine (0.109 ml, 0.622 mmol) is added in the dichloromethane (2072 μ l) in 20 mL bottles.Add 4- isocyanic acids
Root closes methyl benzoate (47.7 mg, 0.269 mmol), the mixture 2 hours is stirred at room temperature and by rotary evaporation
Method is concentrated.Purify residue to provide title compound by normal-phase chromatography method.
Embodiment 14
N- (4- cyano-phenyls) -3- (pyridin-3-yl) azetidine -1- formamides
Title compound is prepared as described in Example 13, and 4- isocyanato- benzene first is substituted with 4- isocyanato-s benzonitrile
Sour methyl esters.
Embodiment 15
4- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) butyl] piperidines -1- t-butyl formates
Title compound is prepared as described in embodiment 1C, 3- is substituted with 4- (4- aminobutyls) piperidines -1- t-butyl formates
(4- amino-benzene oxygens) azetidine -1- t-butyl formates.
Embodiment 49
3- (pyridin-3-yl)-N- { 4- [(tetrahydrofuran -3- ylmethyls) carbamoyl] phenyl } azetidine -1-
Formamide
Embodiment 49A
4- amino-N- ((tetrahydrofuran -3- bases) methyl) benzamide
Title compound is prepared as described in embodiment 1E, N- (4- (azetidins are substituted with (tetrahydrofuran -3- bases) methylamine
Alkane -3- bases epoxide) phenyl) -3- (pyridin-3-yl) azetidine -1- formamides and with PABA substitute (S) -2-
Methylbutanoic acid.
Embodiment 49B
3- (pyridin-3-yl)-N- { 4- [(tetrahydrofuran -3- ylmethyls) carbamoyl] phenyl } azetidine -1-
Formamide
Title compound is prepared as described in embodiment 1C, with 4- amino-N- ((tetrahydrofuran -3- bases) methyl) benzamide
Substitute 3- (4- amino-benzene oxygens) azetidine -1- t-butyl formates.
Embodiment 50
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] phenyl } azacyclo-
Butane -1- formamides
Embodiment 50A
4- (4- (3- (pyridin-3-yl) azetidine -1- formamidos) phenyl) piperidines -1- t-butyl formates
Title compound is prepared as described in embodiment 1C, 3- is substituted with 4- (4- aminophenyls) piperidines -1- t-butyl formates
(4- amino-benzene oxygens) azetidine -1- t-butyl formates.
Embodiment 50B
N- (4- (piperidin-4-yl) phenyl) -3- (pyridin-3-yl) azetidine -1- formamides
Title compound is prepared as described in embodiment 1D, with 4- (4- (3- (pyridin-3-yl) azetidine -1- formamides
Base) phenyl) piperidines -1- t-butyl formates replacement 3- (4- (3- (pyridin-3-yl) azetidine -1- formamidos) phenoxy group)
Azetidine -1- t-butyl formates.
Embodiment 50C
N- (4- { 1- [(2S) -2- methylbutyryls base] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides
Title compound is prepared as described in embodiment 1E, with N- (4- (piperidin-4-yl) phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides replacement N- (4- (azetidine -3- bases epoxide) phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides and with tetrahydrochysene -2H- pyrans -4- guanidine-acetic acids substitute (S) -2-Methyl Butyric Acid.
Table 3.
Following examples substantially are prepared as described in embodiment 50, with suitable amine and embodiment 50C in embodiment 50A
Middle suitable carboxylic acid is substituted.By some products of flash chromatography, and pass through rp-hplc method and purify other products.Cause
This, some embodiments are separated into trifluoroacetate.
Embodiment 59
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] tertiary fourth of pyrrolidines -1- formic acid
Ester
Title compound is prepared as described in embodiment 1C, is substituted with 3- (4- aminophenyls) pyrrolidines -1- t-butyl formates
3- (4- amino-benzene oxygens) azetidine -1- t-butyl formates.
Embodiment 60
(3R) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1-
T-butyl formate
As embodiment 1A-C prepares title compound, with (R) -3- hydroxyl pyrrolidine -1- t-butyl formate alternate embodiments
3- hydroxy azetidine -1- t-butyl formates in 1A.
Embodiment 61
(3S) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1-
T-butyl formate
Title compound is prepared as described in embodiment 1A-C, is substituted with (S) -3- hydroxyl pyrrolidine -1- t-butyl formates real
Apply the 3- hydroxy azetidine -1- t-butyl formates in a 1A.
Embodiment 62
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] azetidine -1- formic acid
The tert-butyl ester
Title compound is prepared as described in embodiment 1C, with 3- (4- aminophenyls) azetidine -1- t-butyl formates
Substitute 3- (4- amino-benzene oxygens) azetidine -1- t-butyl formates.
Embodiment 63
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] azetidine -1- first
Tert-butyl acrylate
Title compound is prepared as described in embodiment 1C.
Embodiment 112
4- [4- ({ [3- (2- chloropyridine -3- bases) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester
Title compound is prepared as described in embodiment 1C, 3- is substituted with 4- (4- aminophenyls) piperidines -1- t-butyl formates
(4- amino-benzene oxygens) azetidine -1- t-butyl formates and with 3- (azetidine -3- bases) -2- chloropyridines substitute 3-
(azetidine -3- bases) pyridine dihydrochloride.
Embodiment 113
4- [4- ({ [3- (4- chloropyridine -3- bases) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester
Title compound is prepared as described in embodiment 1C, 3- is substituted with 4- (4- aminophenyls) piperidines -1- t-butyl formates
(4- amino-benzene oxygens) azetidine -1- t-butyl formates and with 3- (azetidine -3- bases) -4- chloropyridines substitute 3-
(azetidine -3- bases) pyridine dihydrochloride.
Embodiment 116
4- [4- ({ [3- (2- fluorine pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] piperidines -1- formic acid uncles
Butyl ester
Title compound is prepared as described in embodiment 1C, 3- is substituted with 4- (4- aminophenyls) piperidines -1- t-butyl formates
(4- amino-benzene oxygens) azetidine -1- t-butyl formates and with 3- (azetidine -3- bases) -2- fluorine pyridine substitute 3-
(azetidine -3- bases) pyridine dihydrochloride.
Embodiment 157
N- { 4- [1- (2- methyl-propyls) -1H- pyrazoles -4- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides
Embodiment 157A
N- (4- bromophenyls) -3- (pyridin-3-yl) azetidine -1- formamides
Title compound is prepared as described in Example 13, and 4- isocyanato- benzene is substituted with the bromo- 4- isocyanato-s benzene of 1-
Methyl formate.
Embodiment 157B
N- { 4- [1- (2- methyl-propyls) -1H- pyrazoles -4- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides
Title compound is prepared as described in embodiment 9A, with 1- isobutyl groups -4- (4,4,5,5- tetramethyl -1,3,2- dioxies
Miscellaneous boron heterocycle pentane -2- bases) -1H- pyrazoles replacement 4- (4,4,5,5- tetramethyl -1,3,2- dioxaborolan alkane -2- bases) -
5,6- dihydropyridines -1 (2H)-t-butyl formate and with N- (4- bromophenyls) -3- (pyridin-3-yl) azetidine -1- formyls
Amine substitutes the bromo- 4- nitrobenzene of 1-.
Embodiment 158
N- [4- (1- propyl group -1H- pyrazoles -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides
Title compound is prepared as described in embodiment 157, with 1- propyl group -4- (4,4,5,5- tetramethyl -1,3,2- dioxas
Boron heterocycle pentane -2- bases) 1- isobutyl groups -4- (4,4,5,5- tetramethyls -1,3,2- in -1H- pyrazoles alternate embodiments 157B
Dioxaborolan alkane -2- bases) -1H- pyrazoles.
Embodiment 162
4- (pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } phenyl)
Piperazine -1- formamides
Embodiment 162A
4- (piperidin-4-yl epoxide) aniline
Title compound is prepared as described in embodiment 1D, is substituted with 4- (4- amino-benzene oxygens) piperidines -1- t-butyl formates
3- (4- (3- (pyridin-3-yl) azetidine -1- formamidos) phenoxy group) azetidine -1- t-butyl formates.
Embodiment 162B
1- (4- (4- amino-benzene oxygens) piperidin-1-yl) -2- (tetrahydrochysene -2H- pyrans -4- bases) ethyl ketone
Title compound is prepared as described in embodiment 1E, N- (4- (azacyclo-s are substituted with 4- (piperidin-4-yl epoxide) aniline
Butane -3- bases epoxide) phenyl) -3- (pyridin-3-yl) azetidine -1- formamides and 2- (tetrahydrochysene -2H- pyrans -4- bases) second
Acid substitutes (S) -2-Methyl Butyric Acid.
Embodiment 162C
4- (pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } phenyl)
Piperazine -1- formamides
Prepare title compound as described in embodiment 1C, with 1- (4- (4- amino-benzene oxygens) piperidin-1-yl) -2- (tetrahydrochysene -
2H- pyrans -4- bases) ethyl ketone substitutes 3- (4- amino-benzene oxygens) azetidine -1- t-butyl formates and with 1- (pyridin-3-yl)
Piperazine substitutes 3- (azetidine -3- bases) pyridine dihydrochloride.
Embodiment 231
N- { 4- [1- (cyclopentyl-methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides
Embodiment 231A
4- (4- (3- (pyridin-3-yl) azetidine -1- formamidos) phenyl) piperidines -1- t-butyl formates
Title compound is prepared as described in embodiment 1C, 3- is substituted with 4- (4- aminophenyls) piperidines -1- t-butyl formates
(4- amino-benzene oxygens) azetidine -1- t-butyl formates.
Embodiment 231B
N- (4- (piperidin-4-yl) phenyl) -3- (pyridin-3-yl) azetidine -1- formamides
Title compound is prepared as described in embodiment 1D, with 4- (4- (3- (pyridin-3-yl) azetidine -1- formamides
Base) phenyl) piperidines -1- t-butyl formates replacement 3- (4- (3- (pyridin-3-yl) azetidine -1- formamidos) phenoxy group)
Azetidine -1- t-butyl formates.
Embodiment 231C
N- { 4- [1- (cyclopentyl-methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides
N- (4- (piperidin-4-yl) phenyl) -3- (pyridin-3-yl) azetidine -1- formyls are added in 20 mL bottles
Amine, the double trifluoroacetic acids (67 mg, 0.12 mmol) being dissolved in methyl alcohol (2.0 mL), are subsequently adding and are dissolved in methyl alcohol
Pentamethylene formaldehyde (13 mg, 0.13 mmol) in (0.45 mL), is subsequently adding pure acetic acid (68 μ L, 1.2 mmol).
Reactant mixture is shaken at 70 DEG C 2 hours.Afterwards, MP- Cyanoborohydride (272 mg, 2-3 mmol/g) resin is added
And mixture obtained by being shaken at 70 DEG C is overnight.Filtering reactant mixture is simultaneously concentrated to dryness.Residue is dissolved in 1:1
Purified in DMSO/ methyl alcohol and by reverse phase chromatography.
Table 4.
Following examples substantially are prepared as described in embodiment 231, with suitable amine and embodiment in embodiment 231A
Substituted with suitable aldehyde in 231C.By some products of flash chromatography, and pass through rp-hplc method and purify other products.
Therefore, some embodiments are separated into trifluoroacetate.
Embodiment 336
N- [4- (1- benzoyl piperidine -4- bases) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides
Embodiment 336A
4- (4- (3- (pyridazine -3- bases) azetidine -1- formamidos) phenyl) piperidines -1- t-butyl formates
Title compound is prepared as described in embodiment 1C, 3- is substituted with 4- (4- aminophenyls) piperidines -1- t-butyl formates
(4- amino-benzene oxygens) azetidine -1- t-butyl formates and with 3- (azetidine -3- bases) pyridazine hydrochloride substitute 3-
(azetidine -3- bases) pyridine dihydrochloride.
Embodiment 336B
N- (4- (piperidin-4-yl) phenyl) -3- (pyridazine -3- bases) azetidine -1- formamides
Title compound is prepared as described in embodiment 1D, with 4- (4- (3- (pyridazine -3- bases) azetidine -1- formamides
Base) phenyl) piperidines -1- t-butyl formates replacement 3- (4- (3- (pyridin-3-yl) azetidine -1- formamidos) phenoxy group)
Azetidine -1- t-butyl formates.
Embodiment 336C
N- [4- (1- benzoyl piperidine -4- bases) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides
Title compound is prepared as described in embodiment 1E, with N- (4- (piperidin-4-yl) phenyl) -3- (pyridazine -3- bases) nitrogen
Azetidine -1- formamides replacement N- (4- (azetidine -3- bases epoxide) phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides and with benzoic acid substitute (S) -2-Methyl Butyric Acid.
Table 5.
Following examples substantially are prepared as described in embodiment 336, is substituted with suitable carboxylic acid in embodiment 336C.
| Embodiment | Title | MS | |
| 337 | N- { 4- [1- (2- fluoro benzoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 338 | N- { 4- [1- (2- methyl benzoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 339 | N- { 4- [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 340 | N- { 4- [1- (cyclopropyl carbonyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 341 | N- [4- (1- Acetylpiperidin -4- bases) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 342 | N- { 4- [1- (3,3- dimethylbutanoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 343 | N- { 4- [1- (cyclobutyl carbonyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 344 | 3- (pyridazine -3- bases)-N- { 4- [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] phenyl } azetidine -1- formamides | ||
| 345 | 3- (pyridazine -3- bases)-N- { 4- [1- (3,3,3- trifluoros propiono) piperidin-4-yl] phenyl } azetidine -1- formamides | ||
| 346 | N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 347 | N- { 4- [1- (Cyclopropyl-acetyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides |
Embodiment 348
N- { 4- [(1- benzoyl piperidine -4- bases) methyl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine
Embodiment 348A
4- (pyridin-4-yl methyl) aniline
Title compound is prepared as described in embodiment 1B, 3- (4-nitrophenoxy) is substituted with 4- (4- nitrobenzyls) pyridine
Azetidine -1- t-butyl formates.
Embodiment 348B
The fluoro- N- of 2,2,2- tri- (4- (pyridin-4-yl methyl) phenyl) acetamide
By 4- (pyridin-4-yl methyl) aniline (21.6 g, 117 mmol) and triethylamine (19.61 ml, 141
Mmol) solution in dichloromethane (586 ml) is cooled to 0 DEG C.Trifluoro second is added dropwise over by charging hopper through 20 minutes
Acid anhydrides (19.87 ml, 141 mmol).The mixture is stirred at 0 DEG C 1 hour, be then stirred at room temperature 2 hours.So
After be concentrated in vacuo the reactant mixture, residue is providing title compound as obtained by normal phase column chromatography method is purified.
Embodiment 348C
The fluoro- N- of 2,2,2- tri- (4- (piperidin-4-ylmethyl) phenyl) acetamide
By the fluoro- N- of 2,2,2- tri- (4- (pyridin-4-yl methyl) phenyl) acetamides (28.5 g, 102 mmol) and acetic acid
(205 ml) is added in the platinum oxide (IV) (3.42 g, 15.06 mmol) in 500 mL stainless steel pressures bottle and 40
The mixture is stirred 16 hours under psi.By the nylon membrane filtration mixture and it is concentrated in vacuo；And dissolve gained residue
In the methyl alcohol (100 mL) and it is poured onto ether (600 mL).Filtering precipitate, is washed and dried to provide mark with ether
Topic compound.
Embodiment 348D
4- (4- aminobenzyls) piperidines -1- t-butyl formates
By the fluoro- N- of 2,2,2- tri- (4- (piperidin-4-ylmethyl) phenyl) acetamide (26.4 g, 92 mmol) in dichloro
Solution in methane (369 ml) is cooled to 0 DEG C and is slowly added to triethylamine (19.28 ml, 138 mmol).Through 10 minutes
By charging hopper to addition di-tert-butyl dicarbonate (22.14 g, 101 mmol)/dichloromethane (75 in resulting solution
ml).0 DEG C of mixture is stirred 2 hours and slowly warmed overnight.The reactant mixture is cooled to 0 DEG C, with 1 N hydrogen-oxygens
Change sodium (100 ml) treatment, warm to room temperature and stir 1 hour.Separate bilayer and with water and salt water washing organic matter, use sulfuric acid
Magnesium dries, filters and be concentrated in vacuo.Purify residue to provide title compound by normal-phase chromatography method.
Embodiment 348E
4- (4- (3- (pyridazine -3- bases) azetidine -1- formamidos) benzyl) piperidines -1- t-butyl formates
Title compound is prepared as described in embodiment 1C, 3- is substituted with 4- (4- aminobenzyls) piperidines -1- t-butyl formates
(4- amino-benzene oxygens) azetidine -1- t-butyl formates and with 3- (azetidine -3- bases) pyridazine hydrochloride substitute 3-
(azetidine -3- bases) pyridine dihydrochloride.
Embodiment 348F
N- (4- (piperidin-4-ylmethyl) phenyl) -3- (pyridazine -3- bases) azetidine -1- formamides
Title compound is prepared as described in embodiment 1D, with 4- (4- (3- (pyridazine -3- bases) azetidine -1- formamides
Base) benzyl) piperidines -1- t-butyl formates replacement 3- (4- (3- (pyridin-3-yl) azetidine -1- formamidos) phenoxy group)
Azetidine -1- t-butyl formates.
Embodiment 348G
N- { 4- [(1- benzoyl piperidine -4- bases) methyl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine
Title compound is prepared as described in embodiment 1E, with N- (4- (piperidin-4-ylmethyl) phenyl) -3- (pyridazine -3-
Base) azetidine -1- formamides replacement N- (4- (azetidine -3- bases epoxide) phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides and with benzoic acid substitute (S) -2-Methyl Butyric Acid.
Table 6.
Following examples are substantially prepared as described in Example 1, and with 1,3- dihydro-2 h-pyrroles, simultaneously [3,4-c] pyridine is substituted
Isoindoline in embodiment 1A simultaneously uses the suitable amine as described in embodiment 1C.
| Embodiment | Title | MS | |
| 349 | N- (4- { [1- (2- fluoro benzoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 350 | N- (4- { [1- (2,2- Dimethylpropanoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 351 | N- (4- { [1- (3,3- dimethylbutanoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 352 | N- (4- { [1- (2- ethylbutanoyls base) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 353 | 3- (pyridazine -3- bases)-N- (4- { [1- (4,4,4- trifluoros bytyry) piperidin-4-yl] methyl } phenyl) azetidine -1- formamides | ||
| 354 | N- (4- { [1- (2- methylpropionyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 355 | N- { 4- [(1- Acetylpiperidin -4- bases) methyl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 356 | N- [4- ({ 1- [(2S) -2- methylbutyryls base] piperidin-4-yl } methyl) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides | ||
| 357 | N- [4- ({ 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } methyl) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides |
Claims (8)
1. the upper acceptable salt of formula (IA) compound, or its treatment,
Formula (IA)；
Wherein
X1It is N and X2It is CR1；Or
X1It is CR1And X2It is N；Or
X1It is CR1And X2It is CR1；
Y1For
WhereinThe tie point with carbonyl is represented,Represent the tie point with nitrogenous heteroaryl；
R1, every time occur when, independently selected from hydrogen, alkyl, alkenyl, alkynyl, haloalkyl, hydroxy alkyl, alkoxy, OH,
NH2、CN、NO2, F, Cl, Br and I；
R2Independently selected from C4-C6- alkyl, C4-C6- alkenyl, C4-C6- alkynyl, aryl, 3-12 circle heterocycles base, cycloalkyl and cyclenes
Base；Wherein R2In C4-C6- alkyl, C4-C6- alkenyl and C4-C6- alkynyl is each independently selected by one or more from following
Substitution base substitution：R3、OR3、SR3、S(O)R3、SO2R3、C(O)R3、CO(O)R3、OC(O)R3、OC(O)OR3、NH2、NHR3、N
(R3)2、NHC(O)R3、NR3C(O)R3、NHS(O)2R3、NR3S(O)2R3、NHC(O)OR3、NR3C(O)OR3、NHC(O)NH2、NHC
(O)NHR3、NHC(O)N(R3)2、NR3C(O)NHR3、NR3C(O)N(R3)2、C(O)NH2、C(O)NHR3、C(O)N(R3)2、C(O)
NHOH、C(O)NHOR3、C(O)NHSO2R3、C(O)NR3SO2R3、SO2NH2、SO2NHR3、SO2N(R3)2、C(O)H、C(O)OH、C
(N)NH2、C(N)NHR3、C(N)N(R3)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R2In virtue
Base, 3-12 circle heterocycles base, cycloalkyl and cycloalkenyl group are each optionally independently selected by one or more from following substitution base substitution：
R4、OR4、SR4、S(O)R4、SO2R4、C(O)R4、CO(O)R4、OC(O)R4、OC(O)OR4、NH2、NHR4、N(R4)2、NHC(O)R4、
NR4C(O)R4、NHS(O)2R4、NR4S(O)2R4、NHC(O)OR4、NR4C(O)OR4、NHC(O)NH2、NHC(O)NHR4、NHC(O)N
(R4)2、NR4C(O)NHR4、NR4C(O)N(R4)2、C(O)NH2、C(O)NHR4、C(O)N(R4)2、C(O)NHOH、C(O)NHOR4、C
(O)NHSO2R4、C(O)NR4SO2R4、SO2NH2、SO2NHR4、SO2N(R4)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR4、C
(N)N(R4)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R3, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, cycloalkyl, cycloalkenyl group and heterocyclic radical；Wherein R3
In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R5、OR5、SR5、S
(O)R5、SO2R5、C(O)R5、CO(O)R5、OC(O)R5、OC(O)OR5、NH2、NHR5、N(R5)2、NHC(O)R5、NR5C(O)R5、NHS
(O)2R5、NR5S(O)2R5、NHC(O)OR5、NR5C(O)OR5、NHC(O)NH2、NHC(O)NHR5、NHC(O)N(R5)2、NR5C(O)
NHR5、NR5C(O)N(R5)2、C(O)NH2、C(O)NHR5、C(O)N(R5)2、C(O)NHOH、C(O)NHOR5、C(O)NHSO2R5、C
(O)NR5SO2R5、SO2NH2、SO2NHR5、SO2N(R5)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR5、C(N)N(R5)2、
CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R3In aryl, cycloalkyl, cycloalkenyl group and heterocyclic radical it is each
Replace from following substitution base is optionally independently selected by one or more from：R6、OR6、SR6、S(O)R6、SO2R6、C(O)R6、CO
(O)R6、OC(O)R6、OC(O)OR6、NH2、NHR6、N(R6)2、NHC(O)R6、NR6C(O)R6、NHS(O)2R6、NR6S(O)2R6、NHC
(O)OR6、NR6C(O)OR6、NHC(O)NH2、NHC(O)NHR6、NHC(O)N(R6)2、NR6C(O)NHR6、NR6C(O)N(R6)2、C
(O)NH2、C(O)NHR6、C(O)N(R6)2、C(O)NHOH、C(O)NHOR6、C(O)NHSO2R6、C(O)NR6SO2R6、SO2NH2、
SO2NHR6、SO2N(R6)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR6、C(N)N(R6)2、CNOH、CNOCH3、OH、CN、N3、
NO2, F, Cl, Br and I；
R4, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R4
In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R7、OR7、SR7、S
(O)R7、SO2R7、C(O)R7、CO(O)R7、OC(O)R7、OC(O)OR7、NH2、NHR7、N(R7)2、NHC(O)R7、NR7C(O)R7、NHS
(O)2R7、NR7S(O)2R7、NHC(O)OR7、NR7C(O)OR7、NHC(O)NH2、NHC(O)NHR7、NHC(O)N(R7)2、NR7C(O)
NHR7、NR7C(O)N(R7)2、C(O)NH2、C(O)NHR7、C(O)N(R7)2、C(O)NHOH、C(O)NHOR7、C(O)NHSO2R7、C
(O)NR7SO2R7、SO2NH2、SO2NHR7、SO2N(R7)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR7、C(N)N(R7)2、
CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；
R5, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R5
In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R8、OR8、SR8、S
(O)R8、SO2R8、NHR8、N(R8)2、C(O)R8、C(O)NH2、C(O)NHR8、C(O)N(R8)2、NHC(O)R8、NR8C(O)R8、
NHSO2R8、NHC(O)OR8、SO2NH2、SO2NHR8、SO2N(R8)2、NHC(O)NH2、NHC(O)NHR8、OH、(O)、C(O)OH、N3、
CN、NH2, F, Cl, Br and I；
R6, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein R6
In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R9、OR9、SR9、S
(O)R9、SO2R9、NHR9、N(R9)2、C(O)R9、C(O)NH2、C(O)NHR9、C(O)N(R9)2、NHC(O)R9、NR9C(O)R9、
NHSO2R9、NHC(O)OR9、SO2NH2、SO2NHR9、SO2N(R9)2、NHC(O)NH2、NHC(O)NHR9、OH、(O)、C(O)OH、N3、
CN、NH2、CF3、CF2CF3, F, Cl, Br and I；
R7, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R8, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
R9, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；
Wherein by R4、R5、R6、R7、R8And R9The cyclic group of expression is independently optionally independently selected by one or more from as follows
Substitution base substitution：R10、OR10、SR10、S(O)R10、C(O)C(O)R10、SO2R10、C(O)R10、CO(O)R10、OC(O)R10、OC
(O)OR10、NH2、NHR10、N(R10)2、NHC(O)R10、NR10C(O)R10、NHS(O)2R10、NR10S(O)2R10、NHC(O)OR10、
NR10C(O)OR10、NHC(O)NH2、NHC(O)NHR10、NHC(O)N(R10)2、NR10C(O)NHR10、NR10C(O)N(R10)2、C(O)
NH2、C(O)NHR10、C(O)N(R10)2、C(O)NHOH、C(O)NHOR10、C(O)NHSO2R10、C(O)NR10SO2R10、SO2NH2、
SO2NHR10、SO2N(R10)2、C(O)H、C(O)OH、C(N)NH2、C(N)NHR10、C(N)N(R10)2、CNOH、CNOCH3、OH、CN、
N3、NO2, F, Cl, Br and I；
R10, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein
R10In alkyl, alkenyl and alkynyl be each optionally independently selected by one or more from following substitution base substitution：R11、OR11、
SR11、S(O)R11、SO2R11、C(O)R11、CO(O)R11、OC(O)R11、OC(O)OR11、NH2、NHR11、N(R11)2、NHC(O)R11、
NR11C(O)R11、NHS(O)2R11、NR11S(O)2R11、NHC(O)OR11、NR11C(O)OR11、NHC(O)NH2、NHC(O)NHR11、
NHC(O)N(R11)2、NR11C(O)NHR11、NR11C(O)N(R11)2、C(O)NH2、C(O)NHR11、C(O)N(R11)2、C(O)NHOH、
C(O)NHOR11、C(O)NHSO2R11、C(O)NR11SO2R11、SO2NH2、SO2NHR11、SO2N(R11)2、C(O)H、C(O)OH、C(N)
NH2、C(N)NHR11、C(N)N(R11)2、CNOH、CNOCH3、OH、(O)、CN、N3、NO2, F, Cl, Br and I；Wherein R10In virtue
Base, heterocyclic radical, cycloalkyl and cycloalkenyl group are each optionally independently selected by one or more from following substitution base substitution：R12、
OR12、SR12、S(O)R12、SO2R12、C(O)R12、CO(O)R12、OC(O)R12、OC(O)OR12、NH2、NHR12、N(R12)2、NHC(O)
R12、NR12C(O)R12、NHS(O)2R12、NR12S(O)2R12、NHC(O)OR12、NR12C(O)OR12、NHC(O)NH2、NHC(O)
NHR12、NHC(O)N(R12)2、NR12C(O)NHR12、NR12C(O)N(R12)2、C(O)NH2、C(O)NHR12、C(O)N(R12)2、C(O)
NHOH、C(O)NHOR12、C(O)NHSO2R12、C(O)NR12SO2R12、SO2NH2、SO2NHR12、SO2N(R12)2、C(O)H、C(O)
OH、C(N)NH2、C(N)NHR12、C(N)N(R12)2、CNOH、CNOCH3、OH、CN、N3、NO2, F, Cl, Br and I；
R11, when occurring every time, independently selected from alkyl, alkenyl, alkynyl, aryl, heterocyclic radical, cycloalkyl and cycloalkenyl group；Wherein
R11In alkyl, alkenyl and alkynyl each optionally replaced by alkyl or alkoxy；Wherein R11In aryl, heterocyclic radical, cycloalkyl
Each optionally replaced by alkyl or alkoxy with cycloalkenyl group；With
R12, it is the alkyl of independent selection when occurring every time.
2. the upper acceptable salt of the compound described in claim 1, or its treatment, wherein X1It is CR1And X2It is CR1。
3. the upper acceptable salt of the compound described in claim 1 or claim 2, or its treatment, wherein R1When occurring every time
It is hydrogen.
4. the upper acceptable salt of the compound described in claim 1, or its treatment, wherein R2It is phenyl；Wherein R2In phenyl it is each
From by OR4Substitution.
5. the upper acceptable salt of the compound described in claim 1, or its treatment, wherein R2It is phenyl；Wherein R2In phenyl it is each
From by R4Substitution.
6. the upper acceptable salt of the compound described in claim 4 or 5, or its treatment, wherein R4It independently is heterocyclic radical.
7. the compound described in claim 1, it is selected from
N- [4- ({ 1- [(2S) -2- methylbutyryls base] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
3- (5- fluorine pyridin-3-yl)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } phenyl)
Azetidine -1- formamides；
N- [4- ({ 1- [(2S) -2- methylbutyryls base] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2R)-tetra oxygen furyl -2- bases carbonyl] piperidin-4-yl } epoxide) phenyl] azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (3,3,3- trifluoro propiono) piperidin-4-yl] epoxide } phenyl) azetidine-
1- formamides；
N- (4- { [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (6- picoline -3- bases)-N- (4- { [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] epoxide } benzene
Base) azetidine -1- formamides；
N- (4- { 1- [(2S) -2- methylbutyryls base] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] -1,2,3,6- tetrahydropyridine -4- bases } benzene
Base) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] -1,2,3,6- tetrahydropyridine -4- bases } benzene
Base) azetidine -1- formamides；
N- { 4- [tetrahydropyridine -4- bases of 1- (2- hydroxy-2-methyls propiono) -1,2,3,6-] phenyl } -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) methyl benzoate；
N- (4- cyano-phenyls) -3- (pyridin-3-yl) azetidine -1- formamides；
4- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) butyl] piperidines -1- t-butyl formates；
N- { 4- [tetrahydropyridine -4- bases of 1- (2,2- dimethylbutanoyl) -1,2,3,6-] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- { 4- [tetrahydropyridine -4- bases of 1- (3,3- dimethylbutanoyl) -1,2,3,6-] phenyl } -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [tetrahydropyridine -4- bases of 1- (3,3,3- trifluoro propiono) -1,2,3,6-] phenyl } azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [tetrahydropyridine -4- bases of 1- (4,4,4- trifluoro bytyry) -1,2,3,6-] phenyl } azepine
Cyclobutane -1- formamides；
N- { 4- [1- (Methoxyacetyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { tetrahydropyridine -4- bases of 1- [(methylsulfanyl) acetyl group] -1,2,3,6- } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- { 4- [tetrahydropyridine -4- bases of 1- (Ethoxyacetyl base) -1,2,3,6-] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { 1- [3- (methylsulfanyl) propiono] -1,2,3,6- tetrahydropyridine -4- bases } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) -1,2,3,6- tetrahydropyridine -4- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [tetrahydropyridine -4- bases of 1- (2- methylpropionyls) -1,2,3,6-] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2R)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } epoxide) phenyl]
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2S)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } epoxide) phenyl]
Azetidine -1- formamides；
N- (4- { [1- (2- hydroxy-2-methyls propiono) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [(2S)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } epoxide) phenyl] azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiophene -2- bases carbonyl) piperidin-4-yl] epoxide } phenyl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- (4- { [1- (thiene-3-yl carbonyl) piperidin-4-yl] epoxide } phenyl) azetidine -1- first
Acid amides；
N- [4- ({ 1- [(1- Acetylpiperidin -4- bases) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ 1- [(2- methylcyclopropyl groups) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- ({ 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- [4- ({ 1- [3- (morpholine -4- bases) propiono] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- ({ 1- [3- (4- methylpiperazine-1-yls) propiono] piperidin-4-yl } epoxide) phenyl] -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ 1- [3- (pyrrolidin-1-yl) propiono] piperidin-4-yl } epoxide) phenyl] azacyclo-
Butane -1- formamides；
N- (4- { [1- (Cyclopropyl-acetyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { [1- (3- methylvaleryls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { [1- (4- methylvaleryls) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [(1- bytyries piperidin-4-yl) epoxide] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (Ethoxyacetyl base) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { [1- (cyclopropyl carbonyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { [1- (Methoxyacetyl) piperidin-4-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [(tetrahydrofuran -3- ylmethyls) carbamoyl] phenyl } azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) piperidin-4-yl] phenyl } azetidine -
1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } phenyl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] piperidin-4-yl } phenyl) azetidine -
1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- methylpropionyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- benzoyl piperidine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoro propiono) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] pyrrolidines -1- t-butyl formates；
(3R) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1- formic acid
The tert-butyl ester；
(3S) -3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] pyrrolidines -1- formic acid
The tert-butyl ester；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] tertiary fourth of azetidine -1- formic acid
Ester；
3- [4- ({ [3- (pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenoxy group] azetidine -1- formic acid uncles
Butyl ester；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] phenyl } azetidin
Alkane -1- formamides；
N- { 4- [1- (2- methylpropionyls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } phenyl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } phenyl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- { 4- [1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- (1- benzoyl pyrrole compound alkane -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoro propiono) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- { 4- [1- (cyclopropyl carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- [4- (1- bytyries pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] epoxide } benzene
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (2- methylpropionyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3R) -1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide) benzene
Base] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3R) -1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide) benzene
Base] azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [(3R) -1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- benzoyl pyrrole compound alkane -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (3,3,3- trifluoro propiono) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (cyclopropyl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- [4- ({ (3R) -1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- bytyries pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) pyrrolidin-3-yl] epoxide } benzene
Base) azetidine -1- formamides；
N- (4- { [(3S) -1- (2- methylpropionyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3S) -1- [(2S)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide) benzene
Base] azetidine -1- formamides；
3- (pyridin-3-yl)-N- [4- ({ (3S) -1- [(2R)-tetrahydrofuran -2- bases carbonyl] pyrrolidin-3-yl } epoxide) benzene
Base] azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (tetrahydrofuran -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3S) -1- (Cyclopropyl-acetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [(3S) -1- (2- hydroxy-2-methyls propiono) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3S) -1- benzoyl pyrrole compound alkane -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- (4- { [(3S) -1- (3,3,3- trifluoro propiono) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3S) -1- (cyclopropyl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- [4- ({ (3S) -1- [(2S) -2- methylbutyryls base] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3S) -1- bytyries pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrochysene -2H- pyrans -4- bases acetyl group) azetidine -3- bases] phenyl } azepine
Cyclobutane -1- formamides；
N- { 4- [1- (2- methylpropionyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- (4- { 1- [(2S)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } phenyl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(2R)-tetrahydrofuran -2- bases carbonyl] azetidine -3- bases } phenyl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- bases carbonyl) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- { 4- [1- (Cyclopropyl-acetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- hydroxy-2-methyls propiono) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- benzoyl azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (3,3,3- trifluoro propiono) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- { 4- [1- (cyclopropyl carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { 1- [(2S) -2- methylbutyryls base] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- [4- (1- bytyry azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
4- [4- ({ [3- (2- chloropyridine -3- bases) azetidine -1- bases] carbonyl } amino) phenyl] tertiary fourth of piperidines -1- formic acid
Ester；
4- [4- ({ [3- (4- chloropyridine -3- bases) azetidine -1- bases] carbonyl } amino) phenyl] tertiary fourth of piperidines -1- formic acid
Ester；
N- (4- { [1- (Cyclopropyl-acetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (furans -2- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
4- [4- ({ [3- (2- fluorine pyridin-3-yl) azetidine -1- bases] carbonyl } amino) phenyl] tertiary fourth of piperidines -1- formic acid
Ester；
N- { 4- [(1- valeryl azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- ({ 1- [(2- methoxy ethoxies) acetyl group] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [1- (Ethoxyacetyl base) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (Methoxyacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (3- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- ({ 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] azetidine -3- bases } epoxide) phenyl] -3-
(pyridin-3-yl) azetidine -1- formamides；
N- (4- { [1- (2,3- dimethylbutanoyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (4- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- ({ 1- [(2- methylcyclopropyl groups) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (4,4,4- trifluoro bytyry) azetidine -3- bases] epoxide } phenyl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (2- methylpropionyls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (2,2- Dimethylpropanoyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [(1- bytyry azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [(1- propiono azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { [1- (2,2- dimethylbutanoyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [1- (3- methylbutyryls base) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (3,3,3- trifluoro propiono) azetidine -3- bases] epoxide } phenyl) azacyclo-
Butane -1- formamides；
N- [4- ({ 1- [(1- methylcyclopropyl groups) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [1- (2- methylvaleryls) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [(1- acetyl group azetidine -3- bases) epoxide] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { [1- (Cyclohexylacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (cyclohexyl-carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (cyclopropyl carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiophene -2- bases carbonyl) azetidine -3- bases] epoxide } phenyl) azetidin
Alkane -1- formamides；
N- (4- { [1- (cyclopentylcarbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [1- (morpholine -4- bases acetyl group) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3-thiazoles -5- bases carbonyl) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- [4- ({ 1- [(3,5- dimethyl -1,2- oxazole -4- bases) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyrroles
Pyridine -3- bases) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (thiene-3-yl carbonyl) azetidine -3- bases] epoxide } phenyl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3-thiazoles -4- bases carbonyl) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- (4- { [1- (1,2- oxazole -5- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ 1- [(4- methylpiperazine-1-yls) acetyl group] azetidine -3- bases } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [1- (N, N- dimethyl-β-alanyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- (4- { [1- (furans -3- bases carbonyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- ({ 1- [(1- methylcyclohexyls) carbonyl] azetidine -3- bases } epoxide) phenyl] -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [1- (Cyclopentylacetyl) azetidine -3- bases] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (1,3-thiazoles -2- bases carbonyl) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [1- (pyrrolidin-1-yl acetyl group) azetidine -3- bases] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
3- (2- fluorine pyridin-3-yl)-N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } azetidine-
1- formamides；
N- { 4- [1- (2- methyl-propyls) -1H- pyrazoles -4- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- propyl group -1H- pyrazoles -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { 1- [(3S)-tetrahydrofuran -3- bases carbonyl] piperidin-4-yl } phenyl) azetidine -
1- formamides；
3- (4- chloropyridine -3- bases)-N- (4- { 1- [(3S)-tetra oxygen furyl -3- bases carbonyl] piperidin-4-yl } phenyl) azetidin
Alkane -1- formamides；
3- (2- chloropyridine -3- bases)-N- { 4- [1- (2- hydroxy-2-methyls propiono) piperidin-4-yl] phenyl } azetidine -
1- formamides；
N- [4- (1- valeryls piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(1S, 4R)-two ring [221] hept- 2- bases acetyl group] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- { 4- [1- (4- methylvaleryls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methylvaleryls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- ethoxy-cs acyl group) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2,2- dimethylbutanoyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3,3- dimethylbutanoyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2,2- Dimethylpropanoyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- (1- bytyries piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Ethoxyacetyl base) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methylbutyryls base) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (N- acetyl group-L- leucyl-s) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (cyclohexyl-carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Cyclohexylacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoro bytyry) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- { 4- [1- (cyclopentylcarbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (furans -3- bases carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- Acetylpiperidin -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) piperidin-4-yl] phenyl } azetidine -1- formamides；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (morpholine -4- bases acetyl group) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) piperidin-4-yl] phenyl } azetidine -1- formamides；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (furans -2- bases carbonyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- (1- propionos piperidin-4-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (pyrrolidin-1-yl acetyl group) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (1,3-thiazoles -2- bases carbonyl) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- { 4- [1- (Cyclopentylacetyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2,3- dimethylbutanoyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- (1- valeryl azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] azetidine -3- bases } phenyl) -3- (pyridine -
3- yls) azetidine -1- formamides；
N- { 4- [1- (4- methylvaleryls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (3- methylvaleryls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (3- ethoxy-cs acyl group) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2,2- dimethylbutanoyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (2,2- Dimethylpropanoyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (Ethoxyacetyl base) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (3- methylbutyryls base) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (N- acetyl group-L- leucyl-s) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；N- (4- { 1- [(2- methoxy ethoxies) acetyl group] azetidine -3- bases } phenyl) -3- (pyridine -3-
Base) azetidine -1- formamides；
N- { 4- [1- (cyclohexyl-carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (Cyclohexylacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoro bytyry) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- { 4- [1- (cyclopentylcarbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (furans -3- bases carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- [4- (1- acetyl group azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) azetidine -3- bases] phenyl } azetidine -1- first
Acid amides；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [1- (morpholine -4- bases acetyl group) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) azetidine -3- bases] phenyl } azetidine -1- first
Acid amides；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- [4- (1- propiono azetidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] azetidine -3- bases } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (1,3-thiazoles -2- bases carbonyl) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- { 4- [1- (Cyclopentylacetyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2,3- dimethylbutanoyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
N- { 4- [1- (cyclopentyl-methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (cyclohexyl methyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- methyl amyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- methyl-propyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methyl butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- ethyl-butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2,2- dimethyl propyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- methyl butyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- butyl piperidine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- propylpiperdine -4- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2- cyclopropylethyls) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- ylmethyls) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- { 4- [1- (2,2- dimethylbutyl) piperidin-4-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (cyclopentyl-methyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (cyclohexyl methyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3,3- dimethylbutyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (Cvclopropvlmethvl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2- methyl amyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -2- ylmethyls) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- { 4- [1- (2- methyl-propyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (3- methyl butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2- ethyl-butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (2,2- dimethyl propyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2- methyl butyls) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (tetrahydrofuran -3- ylmethyls) azetidine -3- bases] phenyl } azetidine -
1- formamides；
N- { 4- [1- (2,2- dimethylbutyl) azetidine -3- bases] phenyl } -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- (1- valeryls pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methylvaleryls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1S, 4R)-two ring [2.2.1] hept- 2- bases acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
N- { 4- [1- (Cyclopentylacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (morpholine -4- bases acetyl group) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (furans -3- bases carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
3- (pyridin-3-yl)-N- { 4- [1- (pyrrolidin-1-yl acetyl group) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- { 4- [1- (N, N- dimethyl-β-alanyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (1,3-thiazoles -2- bases carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
3- (pyridin-3-yl)-N- { 4- [1- (thiene-3-yl carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- formyls
Amine；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- (4- { 1- [(3 methyl thiophene -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (4,4,4- trifluoro bytyry) pyrrolidin-3-yl] phenyl } azetidine -1- first
Acid amides；
N- (4- { 1- [(4- methylpiperazine-1-yls) acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- { 4- [1- (5- oxo-L-prolyls base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (3- ethoxy-cs acyl group) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- { 4- [1- (4- methylvaleryls) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(1- methylcyclohexyls) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- [4- (1- acetyl-pyrrolidine -3- bases) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Cyclohexylacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- [4- (1- propionos pyrrolidin-3-yl) phenyl] -3- (pyridin-3-yl) azetidine -1- formamides；
N- (4- { 1- [(2- methoxy ethoxies) acetyl group] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { 1- [3- (morpholine -4- bases) propiono] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (2,2- Dimethylpropanoyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { 1- [(5- methylthiophene -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
3- (pyridin-3-yl)-N- { 4- [1- (thiophene -2- bases carbonyl) pyrrolidin-3-yl] phenyl } azetidine -1- formyls
Amine；
N- (4- { 1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- { 4- [1- (furans -2- bases carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { 1- [3- (piperidin-1-yl) propiono] pyrrolidin-3-yl } phenyl) -3- (pyridin-3-yl) azetidines -1-
Formamide；
N- { 4- [1- (Ethoxyacetyl base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2,2- dimethylbutanoyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- { 4- [1- (2- oxos propiono) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (Methoxyacetyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (cyclohexyl-carbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (3- methylbutyryls base) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (cyclopentylcarbonyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- formamides；
N- { 4- [1- (2,3- dimethylbutanoyl) pyrrolidin-3-yl] phenyl } -3- (pyridin-3-yl) azetidine -1- first
Acid amides；
N- (4- { [(3R) -1- valeryls pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- (4- { [(3R) -1- (3- methylvaleryls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [1- (two rings [2.2.1] hept- 2- bases acetyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclopentylacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- ({ (3R) -1- [(2- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (morpholine -4- bases acetyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [(3R) -1- (furans -3- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (pyrrolidin-1-yl acetyl group) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (5- oxo-D- prolyls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (N, N- dimethyl-β-alanyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (1,3-thiazoles -2- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (thiene-3-yl carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azetidin
Alkane -1- formamides；
N- [4- ({ (3R) -1- [(1- methylcyclopropyl groups) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- [4- ({ (3R) -1- [(3 methyl thiophene -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (4,4,4- trifluoro bytyry) pyrrolidin-3-yl] epoxide } phenyl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(4- methylpiperazine-1-yls) acetyl group] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- (4- { [(3R) -1- (5- oxo-L-prolyls base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (3- ethoxy-cs acyl group) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azacyclo-
Butane -1- formamides；
N- (4- { [(3R) -1- (4- methylvaleryls) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- ({ (3R) -1- [(1- methylcyclohexyls) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (Cyclohexylacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [(3R) -1- (N- acetyl group-L- leucyl-s) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- propionos pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -1- formyls
Amine；
N- [4- ({ (3R) -1- [(2- methoxy ethoxies) acetyl group] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -3-
Base) azetidine -1- formamides；
N- [4- ({ (3R) -1- [3- (morpholine -4- bases) propiono] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (2,2- Dimethylpropanoyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- ({ (3R) -1- [(5- methylthiophene -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl)
Azetidine -1- formamides；
3- (pyridin-3-yl)-N- (4- { [(3R) -1- (thiophene -2- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) azetidin
Alkane -1- formamides；
N- [4- ({ (3R) -1- [(1- methyl isophthalic acid H- pyrroles -2- bases) carbonyl] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridine -
3- yls) azetidine -1- formamides；
N- (4- { [(3R) -1- (furans -2- bases carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- [4- ({ (3R) -1- [3- (piperidin-1-yl) propiono] pyrrolidin-3-yl } epoxide) phenyl] -3- (pyridin-3-yl) nitrogen
Azetidine -1- formamides；
N- (4- { [(3R) -1- (Ethoxyacetyl base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [(3R) -1- (3,3- dimethylbutanoyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (2,2- dimethylbutanoyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- (4- { [(3R) -1- (Methoxyacetyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [(3R) -1- (cyclohexyl-carbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [(3R) -1- (3- methylbutyryls base) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidin
Alkane -1- formamides；
N- (4- { [(3R) -1- (cyclopentylcarbonyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azetidine -
1- formamides；
N- (4- { [(3R) -1- (2,3- dimethylbutanoyl) pyrrolidin-3-yl] epoxide } phenyl) -3- (pyridin-3-yl) azepine
Cyclobutane -1- formamides；
N- [4- (1- benzoyl piperidine -4- bases) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides；
N- { 4- [1- (2- fluoro benzoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- { 4- [1- (2- methyl benzoyls) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- { 4- [1- (2,2- Dimethylpropanoyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine；
N- { 4- [1- (cyclopropyl carbonyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- [4- (1- Acetylpiperidin -4- bases) phenyl] -3- (pyridazine -3- bases) azetidine -1- formamides；
N- { 4- [1- (3,3- dimethylbutanoyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formyls
Amine；
N- { 4- [1- (cyclobutyl carbonyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
3- (pyridazine -3- bases)-N- { 4- [1- (4,4,4- trifluoro bytyry) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
3- (pyridazine -3- bases)-N- { 4- [1- (3,3,3- trifluoro propiono) piperidin-4-yl] phenyl } azetidine -1- formyls
Amine；
N- (4- { 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } phenyl) -3- (pyridazine -3- bases) azetidine -1- first
Acid amides；
N- { 4- [1- (Cyclopropyl-acetyl) piperidin-4-yl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- { 4- [(1- benzoyl piperidine -4- bases) methyl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- (4- { [1- (2- fluoro benzoyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -1- first
Acid amides；
N- (4- { [1- (2,2- Dimethylpropanoyl) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- (4- { [1- (3,3- dimethylbutanoyl) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- (4- { [1- (2- ethylbutanoyls base) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -1- first
Acid amides；
3- (pyridazine -3- bases)-N- (4- { [1- (4,4,4- trifluoro bytyry) piperidin-4-yl] methyl } phenyl) azetidine -
1- formamides；
N- (4- { [1- (2- methylpropionyls) piperidin-4-yl] methyl } phenyl) -3- (pyridazine -3- bases) azetidine -1- first
Acid amides；
N- { 4- [(1- Acetylpiperidin -4- bases) methyl] phenyl } -3- (pyridazine -3- bases) azetidine -1- formamides；
N- [4- ({ 1- [(2S) -2- methylbutyryls base] piperidin-4-yl } methyl) phenyl] -3- (pyridazine -3- bases) azetidine -
1- formamides；
N- [4- ({ 1- [(1- methylcyclopropyl groups) carbonyl] piperidin-4-yl } methyl) phenyl] -3- (pyridazine -3- bases) azetidin
Alkane -1- formamides；With its pharmaceutically acceptable salt.
8. the compound or the composition of its pharmaceutically acceptable salt of the claim 1 comprising excipient and therapeutically effective amount.
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| US201361779702P | 2013-03-13 | 2013-03-13 | |
| US61/779702 | 2013-03-13 | ||
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| EA201692091A1 (en) | 2014-04-18 | 2017-04-28 | Милленниум Фармасьютикалз, Инк. | CHINOXALINE COMPOUNDS AND THEIR APPLICATION |
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| ES2957464T3 (en) * | 2017-04-14 | 2024-01-19 | Univ Arizona | Compositions and methods for treating pulmonary fibrosis |
| MA51189A (en) | 2017-04-27 | 2020-03-04 | Seattle Genetics Inc | QUATERNARIZED NICOTINAMIDE ADENINE DINUCLEOTIDE RECOVERY ROUTE INHIBITOR CONJUGATES |
| AU2019222644B2 (en) | 2018-02-13 | 2021-04-01 | Gilead Sciences, Inc. | PD-1/PD-L1 inhibitors |
| CN112041311B (en) | 2018-04-19 | 2023-10-03 | 吉利德科学公司 | PD-1/PD-L1 inhibitors |
| AU2019269372A1 (en) | 2018-05-14 | 2020-11-26 | Takeda Pharmaceutical Company Limited | Pharmaceutical salts of pyrimidine derivatives and method of treating disorders |
| EP4234030A3 (en) | 2018-07-13 | 2023-10-18 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| WO2020086556A1 (en) | 2018-10-24 | 2020-04-30 | Gilead Sciences, Inc. | Pd-1/pd-l1 inhibitors |
| AU2020325315A1 (en) * | 2019-08-07 | 2022-03-24 | Aqualung Therapeutics Corp. | Anti-NAMPT antibodies and uses thereof |
| JP2023522949A (en) | 2020-04-23 | 2023-06-01 | オプナ バイオ ソシエテ アノニム | Compounds and methods for modulating CD73 and indications thereof |
| CN116057045A (en) | 2020-06-05 | 2023-05-02 | 金耐特生物制药公司 | Fibroblast growth factor receptor kinase inhibitors |
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Also Published As
| Publication number | Publication date |
|---|---|
| EP2852585A1 (en) | 2015-04-01 |
| CN104684906A (en) | 2015-06-03 |
| CA2873075A1 (en) | 2013-07-14 |
| JP2015516436A (en) | 2015-06-11 |
| WO2013170113A1 (en) | 2013-11-14 |
| MX2014013752A (en) | 2014-12-08 |
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