US2014378449A1PendingUtilityA1
Triazolopyridine jak inhibitor compounds and methods
Est. expiryJun 20, 2028(~1.9 yrs left)· nominal 20-yr term from priority
Inventors:Bing-Yan ZhuMichael SiuSteven R. MagnusonRichard PastorHe HaiyingXiao YisongZheng JifuXu XingZhao JunpingWendy Liu
A61P 9/04A61P 37/00A61P 37/06A61P 7/02A61P 9/10A61P 43/00A61P 7/00A61P 37/02A61P 3/10A61P 9/00A61P 37/08A61P 5/00A61P 25/28A61P 25/16A61P 29/00A61P 35/02A61P 25/00A61P 31/12A61P 25/14A61P 35/00A61P 21/02A61P 19/08A61P 17/00A61P 11/16A61P 19/02A61P 17/06A61P 19/00A61P 13/12A61P 1/16A61K 31/437A61K 31/444A61K 31/541A61K 31/4545A61K 31/506C07D 401/12A61K 31/496C07D 471/04A61K 31/5377A61K 45/06
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Claims
Abstract
A compound of Formula I, enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein R 1 , R 2 , R 3 , R 4 and R 5 are defined herein, are useful as JAK kinase inhibitors. A pharmaceutical composition that includes a compound of Formula I and a pharmaceutically acceptable carrier, adjuvant or vehicle, and methods of treating or lessening the severity of a disease or condition responsive to the inhibition of JAK kinase activity in a patient are disclosed.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of Formula I
enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein:
R 1 is H, C(O)OR a , phenyl or C 1 -C 9 heteroaryl, wherein said phenyl and heteroaryl are optionally substituted by 1 to 6 R 6 ;
R 2 is phenyl, C 1 -C 9 heteroaryl or C 1 -C 9 heterocyclyl, wherein the phenyl, heteroaryl and heterocyclyl are optionally substituted by 1 to 5 R 7 ;
R 3 , R 4 and R 5 are independently H, CH 3 , CH 2 CH 3 , CF 3 , F or Cl, with the proviso that when R 1 is H, then R 4 is H, CH 3 , CH 2 CH 3 , F or Cl;
R 6 is independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, (C 0 -C 6 alkyl)OR a , (C 0 -C 6 alkyl)NR a R b , halo, CN, S(O) 1-2 R a , S(O) 1-2 NR a R b , NR a S(O) 1-2 R b , NR a C(O)R b , NR a C(O)OR b , OC(O)NR a R b , CF 3 (C 0 -C 5 alkyl)C 1 -C 5 heteroaryl, (C 0 -C 5 alkyl)C 1 -C 5 heterocyclyl, (C 0 -C 5 alkyl)C 3 -C 6 cycloalkyl, (C 0 -C 5 alkyl)C 6 -C 9 aryl, C(O)OR a , C(O)(C 0 -C 5 alkyl)NR a R b , C(O)(C 0 -C 5 alkyl)(C 1 -C 5 heterocyclyl), C(O)NR a (C 0 -C 5 alkyl)(C 1 -C 5 heterocyclyl), C(O)NR a (C 0 -C 5 alkyl)(C 3 -C 6 cycloalkyl), C(O)NR a (C 0 -C 5 alkyl)(C 1 -C 5 heteroaryl), C(O)NR a (C 1 -C 5 alkyl)NR a R b , C(O)NR a (C 1 -C 5 alkyl)(C 6 aryl), wherein said alkyl, alkenyl and alkynyl are optionally substituted by 1 to 5 substituents independently selected from OR a , NR c R d , oxo, S(O) 1-2 R a , S(O) 1-2 NR a R b , and halo, and said aryl, heterocyclyl, heteroaryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from (C 0 -C 5 alkyl)OR a , oxo, halo, CF 3 , (C 0 -C 5 alkyl)NR c R d , C 1 -C 4 alkyl and C(O)R c ;
R 7 is independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, (C 0 -C 6 alkyl)OR a , (C 0 -C 6 alkyl)NR a R b , (C 0 -C 6 alkyl)C 1 -C 5 heterocyclyl, C(O)(C 0 -C 6 alkyl)C 1 -C 5 heterocyclyl, (C 0 -C 6 alkyl)(C 6 -C 9 aryl), halo, CF 3 , OCF 3 , C(O)NR a (C 0 -C 6 alkyl)C 1 -C 5 heterocyclyl, C(O)NR a R b , NR a C(O)R b , SO 2 (C 1 -C 6 alkyl), SO 2 NR a R b , S(O) 1-2 R a , S(O)NR a R b , NR a S(O) 1-2 R b , CN, nitro, wherein said alkyl, alkenyl and alkynyl are optionally substituted by 1 to 5 substituents independently selected from oxo and halo, and said aryl and heterocyclyl are optionally substituted by 1 to 5 substituents independently selected from OR a , halo, CF 3 , NR c R d , oxo and C 1 -C 4 alkyl;
R a and R b are independently H, OR c , C(O)O(C 1 -C 6 alkyl), C 1 -C 6 alkyl, C 6 aryl or C 3 -C 6 cycloalkyl, wherein said alkyl, aryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from C 1 -C 4 alkyl, (C 0 -C 3 alkyl)OR c , oxo, halo, NR c R d and C 4 -C 5 heterocyclyl; or
R a and R b together with the atom to which they are attached form a C 1 -C 5 heterocyclyl, optionally substituted by oxo, halo or C 1 -C 3 alkyl; and
R c and R d are independently H, C 1 -C 3 alkyl, C 3 -C 6 cycloalkyl or phenyl, wherein said alkyl, cycloalkyl and phenyl are optionally substituted by 1 to 5 substituents independently selected from halo, CH 3 OH or NH 2 , C(O)O(C 1 -C 6 alkyl) and C(O)NH(C 1 -C 6 alkyl).
2 . The compound of claim 1 , selected from Formula I:
enantiomers, diasteriomers, tautomers or pharmaceutically acceptable salts thereof, wherein:
R 1 is H, C(O)OR a , phenyl or C 1 -C 9 heteroaryl, wherein said phenyl and heteroaryl are optionally substituted by 1 to 6 R 6 ;
R 2 is phenyl, C 1 -C 9 heteroaryl or C 1 -C 9 heterocyclyl, wherein the phenyl, heteroaryl and heterocyclyl are optionally substituted by 1 to 5 R 7 ;
R 3 , R 4 and R 5 are independently H, CH 3 , CH 2 CH 3 , CF 3 , F or Cl, with the proviso that when R 1 is H, then R 4 is H, CH 3 , CH 2 CH 3 , F or Cl;
R 6 is independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, (C 0 -C 6 alkyl)OR a , (C 0 -C 6 alkyl)NR a R b , halo, CN, C 1 -C 5 heteroaryl, C 1 -C 5 heterocyclyl, C 3 -C 6 cycloalkyl, C 6 -C 9 aryl, C(O)OR a , C(O)(C 0 -C 5 alkyl)NR a R b , C(O)(C 0 -C 5 alkyl)(C 1 -C 5 heterocyclyl), C(O)NR a (C 0 -C 5 alkyl)(C 1 -C 5 heterocyclyl), C(O)NR a (C 0 -C 5 alkyl)(C 3 -C 6 cycloalkyl), C(O)NR a (C 0 -C 5 alkyl)(C 1 -C 5 heteroaryl), C(O)NR a (C 1 -C 5 alkyl)NR a R b , C(O)NR a (C 1 -C 5 alkyl)(C 6 aryl), wherein said alkyl, alkenyl and alkynyl are optionally substituted by 1 to 5 substituents independently selected from OR a , NR c R d , oxo and halo, and said aryl, heterocyclyl, heteroaryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from OR a , oxo, halo, CF 3 , NR c R d , C 1 -C 4 alkyl and C(O)(C 1 -C 4 alkyl);
R 7 is independently H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, (C 0 -C 6 alkyl)OR a , (C 0 -C 6 alkyl)NR a R b , (C 0 -C 6 alkyl)(C 6 -C 9 aryl), halo, C(O)NR a R b , NR a C(O)R b , SO 2 (C 1 -C 6 alkyl), SO 2 NR a R b , CN, nitro, wherein said alkyl, alkenyl and alkynyl are optionally substituted by 1 to 5 substituents independently selected from oxo and halo, and said aryl is optionally substituted by 1 to 5 substituents independently selected from OR a , halo, CF 3 , NR c R d and C 1 -C 4 alkyl;
R a and R b are independently H, OR c , C(O)O(C 1 -C 6 alkyl), C 1 -C 6 alkyl, C 6 aryl or C 3 -C 6 cycloalkyl, wherein said alkyl, aryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from C 1 -C 4 alkyl, (C 0 -C 3 alkyl)OR c , oxo, halo, NR c R d and C 4 -C 5 heterocyclyl; or
R a and R b together with the atom to which they are attached form a C 1 -C 5 heterocyclyl; and
R c and R d are independently H, C 1 -C 3 alkyl, C 3 -C 6 cycloalkyl or phenyl, wherein said alkyl, cycloalkyl and phenyl are optionally substituted by 1 to 5 substituents independently selected from halo, CH 3 OH or NH 2 , C(O)O(C 1 -C 6 alkyl) and C(O)NH(C 1 -C 6 alkyl).
3 . The compound of claim 1 , wherein R 1 is phenyl or C 1 -C 9 heteroaryl, wherein said phenyl and heteroaryl are optionally substituted by 1 to 5 R 6 .
4 . The compound of claim 3 , wherein R 1 is phenyl optionally substituted by 1 to 5 R 6 .
5 . The compound of claim 3 , wherein R 1 is C 1 -C 9 heteroaryl optionally substituted by 1 to 5 R 6 .
6 . The compound of claim 5 , wherein said C 1 -C 9 heteroaryl is pyridinyl, imidazolyl, imidazopyridinyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, triazolyl, thiadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl or furopyridinyl, each of which is optionally substituted by 1 to 5 R 6 .
7 . The compound of claim 6 , wherein said C 1 -C 9 heteroaryl is pyridinyl optionally substituted by 1 to 4 R 6 .
8 . The compound of claim 3 , wherein R 6 is independently C 1 -C 6 alkyl, (C 0 -C 6 alkyl)OR a , (C 0 -C 6 alkyl)NR a R b , halo, CN, C 1 -C 5 heteroaryl, C 4 -C 5 heterocyclyl, C 3 -C 6 cycloalkyl, C 6 aryl, C(O)OR a , C(O)(C 0 -C 5 alkyl)NR a R b , C(O)(C 0 -C 5 alkyl)(C 1 -C 5 heterocyclyl), C(O)NR a (C 0 -C 5 alkyl)(C 1 -C 5 heterocyclyl), C(O)NR a (C 0 -C 5 alkyl)(C 3 -C 6 cycloalkyl), C(O)NR a (C 0 -C 5 alkyl)(C 1 -C 5 heteroaryl), C(O)NR a (C 1 -C 5 alkyl)NR a R b , C(O)NR a (C 1 -C 5 alkyl)(C 6 aryl), wherein said alkyl is optionally substituted by 1 to 5 substituents independently selected from OR a , NR c R d , oxo and halo, and said aryl, heterocyclyl, heteroaryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from OR a , oxo, halo, CF 3 , NR c R d , C 1 -C 4 alkyl and C(O)(C 1 -C 4 alkyl).
9 . The compound of claim 8 , wherein R 6 is C 4 -C 5 heterocyclyl optionally substituted by 1 to 5 substituents independently selected from OH, oxo, halo, CF 3 , NR c R d , C 1 -C 4 alkyl and C(O)(C 1 -C 4 alkyl).
10 . The compound of claim 9 , wherein said heterocyclyl is pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, 1,1-dioxotetrahydrothiophenyl, piperidinyl, piperizinyl, tetrahydropyranyl, thianyl, morpholinyl, pyridizinyl or hexahydropyrimidinyl.
11 . The compound of claim 8 , wherein said heterocyclyl is piperidinyl, piperizinyl or morpholinyl.
12 . The compound of claim 8 , wherein R 6 is (C 0 -C 6 alkyl)OR a or (C 0 -C 6 alkyl)NR a R b .
13 . The compound of claim 12 , wherein R 6 is (CO—C 3 alkyl)OR a or (C 0 -C 3 alkyl)NR a R b .
14 . The compound of claim 8 , wherein R 6 is halo.
15 . The compound of claim 14 , wherein R 6 is F or Cl.
16 . The compound of claim 8 , wherein R 6 is C(O)NR a (C 0 -C 5 alkyl)(C 1 -C 5 heterocyclyl), C(O)NR a (C 0 -C 5 alkyl)(C 3 -C 6 cycloalkyl), C(O)NR a (C 0 -C 5 alkyl)(C 1 -C 5 heteroaryl), C(O)NR a (C 1 -C 5 alkyl)NR a R b , C(O)NR a (C 1 -C 5 alkyl)(C 6 aryl), wherein said alkyl is optionally substituted by 1 to 5 substituents independently selected from OR a , NR c R d , oxo and halo, and said aryl, heterocyclyl, heteroaryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from OR a , oxo, halo, CF 3 , NR c R d , C 1 -C 4 alkyl and C(O)(C 1 -C 4 alkyl).
17 . The compound of claim 8 , wherein R 6 is C(O)OR a , C(O)(C 0 -C 5 alkyl)NR a R b or C(O)(C 0 -C 5 alkyl)(C 1 -C 5 heterocyclyl), wherein said alkyl is optionally substituted by 1 to 5 substituents independently selected from OR a , NR c R d , oxo and halo, and said aryl, heterocyclyl, heteroaryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from OR a , oxo, halo, CF 3 , NR c R d , C 1 -C 4 alkyl and C(O)(C 1 -C 4 alkyl).
18 . The compound of claim 1 , wherein R 1 is H.
19 . The compound of claim 1 , wherein R 1 is C(O)OR a , wherein R a is independently H, OR c , C(O)O(C 1 -C 6 alkyl), C 1 -C 6 alkyl, C 6 aryl or C 3 -C 6 cycloalkyl, wherein said alkyl, aryl and cycloalkyl are optionally substituted by 1 to 5 substituents independently selected from C 1 -C 4 alkyl, (C 0 -C 3 alkyl)OR c , oxo, halo, NR c R d and C 4 -C 5 heterocyclyl.
20 . The compound of claim 1 , wherein R 3 , R 4 and R 5 are independently H, CH 3 , CF 3 , or F, with the proviso that when R 1 is H, then R 4 is H, CH 3 or F.
21 . The compound of claim 1 , wherein R 3 , R 4 and R 5 are independently H or F.
22 . The compound of claim 1 , wherein R 3 , R 4 and R 5 are H.
23 . The compound of claim 1 , wherein R 2 is phenyl, C 1 -C 9 heteroaryl or C 3 -C 5 heterocyclyl, wherein the phenyl, heteroaryl and heterocyclyl are optionally substituted by 1 to 5 R 7 .
24 . The compound of claim 23 , wherein R 2 is phenyl optionally substituted by 1 to 5 R 7 .
25 . The compound of claim 24 , wherein R 7 is independently C 1 -C 6 alkyl, (C 0 -C 6 alkyl)OR a , (C 0 -C 6 alkyl)NR a R b , (C 0 -C 6 alkyl)(C 6 -C 9 aryl), halo, C(O)NR a R b , NR a C(O)R b , SO 2 (C 1 -C 6 alkyl), SO 2 NR a R b , CN, nitro, wherein said alkyl is optionally substituted by 1 to 5 substituents independently selected from oxo and halo, and said and said aryl is optionally substituted by 1 to 5 substituents independently selected from OR a , halo, CF 3 , NR c R d and C 1 -C 4 alkyl.
26 . The compound of claim 25 , wherein R 7 is independently C 1 -C 4 alkyl, (C 0 -C 6 alkyl)OR a , (C 0 -C 6 alkyl)NR a R b , halo, NR a C(O)R b , SO 2 (C 1 -C 6 alkyl), SO 2 NR a R b , CN or nitro.
27 . The compound of claim 26 , wherein R 7 is independently NH 2 , OCH 3 , CH 3 , CH 2 CH 3 , CH(CH 3 ) 2 , NO 2 , OCF 3 , S(O) 2 N(CH 3 ) 2 , S(O) 2 NH(CH(CH 3 ) 2 ), S(O) 2 NH(C(CH 3 ) 3 ), CN, CF 3 , F, Cl, NHC(O)CH 3 or S(O) 2 CH 3 .
28 . The compound of claim 23 , wherein R 2 is C 1 -C 9 heteroaryl optionally substituted by 1 to 5 R 7 .
29 . The compound of claim 28 , wherein said C 1 -C 9 heteroaryl is pyridinyl, imidazolyl, imidazopyridinyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, tetrazolyl, furyl, thienyl, isoxazolyl, thiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, oxadiazolyl, triazolyl, thiadiazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl or furopyridinyl, each of which is optionally substituted by 1 to 5 R 7 .
30 . The compound of claim 29 , wherein said C 1 -C 9 heteroaryl is pyridinyl or pyrazolyl optionally substituted by 1 to 5 R 7 .
31 . The compound of claim 30 , wherein R 7 is independently CH 3 , CH 2 (phenyl), CH 2 CH(CH 3 ) 2 , or CF 3 .
32 . The compound of claim 23 , wherein said R 2 is C 3 -C 5 heterocyclyl optionally substituted by 1 to 5 R 7 .
33 . The compound of claim 32 , wherein R 2 is piperidinyl, morpholinyl or piperizinyl optionally substituted by 1 to 5 R 7 .
34 . The compound of claim 34 , wherein R 7 is independently CH 3 , CH 2 CH 3 , OH or OCH 3 .
35 . The compound of claim 1 , wherein R 1 is phenyl, optionally substituted by 1 to 5 R 6 ; and R 2 is phenyl, optionally substituted by 1 to 5 R 7 .
36 . The compound of claim 1 , wherein R 1 is phenyl, optionally substituted by 1 to 5 R 6 ; and R 2 is heterocyclyl, optionally substituted by 1 to 5 R 7 .
37 . The compound of claim 36 , wherein said heterocyclyl is piperidinyl, morpholinyl or piperizinyl.
38 . The compound of claim 1 , wherein R 1 is pyridyl, optionally substituted by 1 to 5 R 6 ; and R 2 is phenyl, optionally substituted by 1 to 5 R 7 .
39 . The compound of claim 1 , wherein R 1 is pyridyl, optionally substituted by 1 to 4 R 6 ; and R 2 is heterocyclyl, optionally substituted by 1 to 5 R 7 .
40 . The compound of claim 39 , wherein said heterocyclyl is piperidinyl, morpholinyl or piperizinyl.
41 . The compound of claim 1 , wherein R 1 is phenyl, optionally substituted by 1 to 5 R 6 ; and R 2 is pyridyl, optionally substituted by 1 to 4 R 7 .
42 . The compound of claim 1 , wherein R 1 is pyridyl, optionally substituted by 1 to 4 R 6 ; and R 2 is pyridyl, optionally substituted by 1 to 4 R 7 .
43 . A compound selected from:
44 . A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier, adjuvant or vehicle.
45 . The composition of claim 43 , further comprising an additional therapeutic agent selected from an anti-proliferative agent, an anti-inflammatory agent, an immunomodulatory agent, a neurotropic factor, an agent for treating cardiovascular disease, an agent for treating liver disease, an anti-viral agent, an agent for treating blood disorders, an agent for treating diabetes, or an agent for treating immunodeficiency disorders.
46 . A pharmaceutical composition comprising a compound of claim 1 in an amount to detectably inhibit JAK2 kinase activity and a pharmaceutically acceptable carrier, adjuvant or vehicle.
47 . The composition of claim 46 , wherein said compound of claim 1 is in an amount to detectably inhibit JAK2 kinase activity and is at least 10 fold or more selective in inhibiting JAK2 kinase activity over inhibiting each of JAK1, JAK3 and Tyk-2 activity.
48 . A method of treating or lessening the severity of a disease or condition responsive to the inhibition of JAK2 kinase activity in a patient, comprising administering to said patient a therapeutically effective amount of a compound of claim 1 .
49 . The method of claim 48 , wherein said disease or condition is cancer, stroke, diabetes, hepatomegaly, cardiovascular disease, multiple sclerosis, Alzheimer's disease, cystic fibrosis, viral disease, autoimmune diseases, atherosclerosis, restenosis, psoriasis, allergic disorders, inflammation, neurological disorders, a hormone-related disease, conditions associated with organ transplantation, immunodeficiency disorders, destructive bone disorders, proliferative disorders, infectious diseases, conditions associated with cell death, thrombin-induced platelet aggregation, liver disease, pathologic immune conditions involving T cell activation, CNS disorders or a myeloproliferative disorder.
50 . The method of claim 49 , wherein said disease or condition is cancer.
51 . The method of claim 49 , wherein said disease is a myeloproliferative disorder.
52 . The method of claim 51 , wherein said myeloproliferative disorder is polycythemia vera, essential thrombocytosis, myelofibrosis or chronic myelogenous leukemia (CML).
53 . The method of claim 50 , wherein said cancer is breast, ovary, cervix, prostate, testis, penile, genitourinary tract, seminoma, esophagus, larynx, gastric, stomach, gastrointestinal, skin, keratoacanthoma, follicular carcinoma, melanoma, lung, small cell lung carcinoma, non-small cell lung carcinoma (NSCLC), lung adenocarcinoma, squamous carcinoma of the lung, colon, pancreas, thyroid, papillary, bladder, liver, biliary passage, kidney, bone, myeloid disorders, lymphoid disorders, hairy cells, buccal cavity and pharynx (oral), lip, tongue, mouth, salivary gland, pharynx, small intestine, colon, rectum, anal, renal, prostate, vulval, thyroid, large intestine, endometrial, uterine, brain, central nervous system, cancer of the peritoneum, hepatocellular cancer, head cancer, neck cancer, Hodgkin's or leukemia.
54 . The method of claim 49 , wherein said cardiovascular disease is restenosis, cardiomegaly, atherosclerosis, myocardial infarction or congestive heart failure.
55 . The method of claim 49 , wherein said neurodegenerative disease is Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and cerebral ischemia, and neurodegenerative disease caused by traumatic injury, glutamate neurotoxicity or hypoxia.
56 . The method of claim 49 , wherein said inflammatory diseases is rheumatoid arthritis, psoriasis, contact dermatitis or delayed hypersensitivity reactions.
57 . The method of claim 48 , further comprising administering a second chemotherapeutic agent.
58 . A kit for treating a disease or disorder responsive to the inhibition of a JAK kinase, comprising:
(a) a first pharmaceutical composition comprising a compound of claim 1 ; and (b) instructions for use.
59 . The kit of claim 58 , further comprising:
(c) a second pharmaceutical composition, comprising a chemotherapeutic agent.
60 . The kit of claim 59 , wherein said instructions comprise instructions for the simultaneous, sequential or separate administration of said first and second pharmaceutical compositions to a patient in need thereof.
61 . The kit of claim 59 , wherein said first and second compositions are contained in separate containers.
62 . The kit of claim 59 , wherein said first and second compositions are contained in the same container.
63 . The compound of claim 1 , selected from the compounds of Examples 1-438.Cited by (0)
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