MX2012004379A - Compuestos de pirrolo[2,3-d]pirimidina. - Google Patents
Compuestos de pirrolo[2,3-d]pirimidina.Info
- Publication number
- MX2012004379A MX2012004379A MX2012004379A MX2012004379A MX2012004379A MX 2012004379 A MX2012004379 A MX 2012004379A MX 2012004379 A MX2012004379 A MX 2012004379A MX 2012004379 A MX2012004379 A MX 2012004379A MX 2012004379 A MX2012004379 A MX 2012004379A
- Authority
- MX
- Mexico
- Prior art keywords
- group
- methyl
- hydrogen
- alkyl
- cyclohexyl
- Prior art date
Links
- 150000004943 pyrrolo[2,3-d]pyrimidines Chemical class 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 222
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- -1 cyano, phenyl Chemical group 0.000 claims description 272
- 229910052739 hydrogen Inorganic materials 0.000 claims description 182
- 239000001257 hydrogen Substances 0.000 claims description 182
- 125000000217 alkyl group Chemical group 0.000 claims description 171
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 120
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 106
- 125000001424 substituent group Chemical group 0.000 claims description 92
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 88
- 150000003839 salts Chemical class 0.000 claims description 83
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 70
- 125000003118 aryl group Chemical group 0.000 claims description 51
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 48
- 125000000623 heterocyclic group Chemical group 0.000 claims description 48
- 125000003545 alkoxy group Chemical group 0.000 claims description 45
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 45
- 238000011282 treatment Methods 0.000 claims description 42
- 125000004076 pyridyl group Chemical group 0.000 claims description 41
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 39
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 35
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 33
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 32
- 108010024121 Janus Kinases Proteins 0.000 claims description 32
- 102000015617 Janus Kinases Human genes 0.000 claims description 32
- 125000005843 halogen group Chemical group 0.000 claims description 31
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 30
- 239000011737 fluorine Substances 0.000 claims description 29
- 229910052731 fluorine Inorganic materials 0.000 claims description 29
- 125000004043 oxo group Chemical group O=* 0.000 claims description 23
- 125000001153 fluoro group Chemical group F* 0.000 claims description 21
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 21
- 125000004193 piperazinyl group Chemical group 0.000 claims description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 16
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 15
- 230000001404 mediated effect Effects 0.000 claims description 15
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 15
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 15
- 125000001188 haloalkyl group Chemical group 0.000 claims description 14
- 208000006673 asthma Diseases 0.000 claims description 13
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 13
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 13
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 13
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 12
- 201000006417 multiple sclerosis Diseases 0.000 claims description 12
- 125000006513 pyridinyl methyl group Chemical group 0.000 claims description 12
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 11
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 11
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 11
- 208000023275 Autoimmune disease Diseases 0.000 claims description 9
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 9
- 208000035475 disorder Diseases 0.000 claims description 9
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 9
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 9
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 9
- 206010020751 Hypersensitivity Diseases 0.000 claims description 8
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 8
- 206010012601 diabetes mellitus Diseases 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 8
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims description 8
- 210000000056 organ Anatomy 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000002102 aryl alkyloxo group Chemical group 0.000 claims description 7
- 125000005167 cycloalkylaminocarbonyl group Chemical group 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 7
- 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 7
- 125000003386 piperidinyl group Chemical group 0.000 claims description 7
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 7
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 7
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 238000002054 transplantation Methods 0.000 claims description 7
- 210000001744 T-lymphocyte Anatomy 0.000 claims description 6
- 206010003246 arthritis Diseases 0.000 claims description 6
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 6
- 125000002393 azetidinyl group Chemical group 0.000 claims description 6
- 201000011510 cancer Diseases 0.000 claims description 6
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 6
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 6
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 5
- 206010052779 Transplant rejections Diseases 0.000 claims description 5
- 208000026935 allergic disease Diseases 0.000 claims description 5
- 230000007815 allergy Effects 0.000 claims description 5
- 230000001363 autoimmune Effects 0.000 claims description 5
- 230000001684 chronic effect Effects 0.000 claims description 5
- 239000003937 drug carrier Substances 0.000 claims description 5
- 208000032839 leukemia Diseases 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 4
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 206010009900 Colitis ulcerative Diseases 0.000 claims description 4
- 206010025323 Lymphomas Diseases 0.000 claims description 4
- 206010035226 Plasma cell myeloma Diseases 0.000 claims description 4
- 201000004681 Psoriasis Diseases 0.000 claims description 4
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 4
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 4
- 230000001154 acute effect Effects 0.000 claims description 4
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 4
- 125000006255 cyclopropyl carbonyl group Chemical group [H]C1([H])C([H])([H])C1([H])C(*)=O 0.000 claims description 4
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 4
- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 4
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 4
- DFVBZOPVGGDURA-MRJYIUEKSA-N C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCCC(O)C1 Chemical compound C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCCC(O)C1 DFVBZOPVGGDURA-MRJYIUEKSA-N 0.000 claims description 3
- 208000011231 Crohn disease Diseases 0.000 claims description 3
- 208000022559 Inflammatory bowel disease Diseases 0.000 claims description 3
- 208000034578 Multiple myelomas Diseases 0.000 claims description 3
- 208000033766 Prolymphocytic Leukemia Diseases 0.000 claims description 3
- 206010060862 Prostate cancer Diseases 0.000 claims description 3
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims description 3
- 206010040047 Sepsis Diseases 0.000 claims description 3
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 3
- 206010046851 Uveitis Diseases 0.000 claims description 3
- 125000003282 alkyl amino group Chemical group 0.000 claims description 3
- 238000010322 bone marrow transplantation Methods 0.000 claims description 3
- 206010006451 bronchitis Diseases 0.000 claims description 3
- 125000006517 heterocyclyl carbonyl group Chemical group 0.000 claims description 3
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 208000027866 inflammatory disease Diseases 0.000 claims description 3
- 201000008482 osteoarthritis Diseases 0.000 claims description 3
- JHHZLHWJQPUNKB-UHFFFAOYSA-N pyrrolidin-3-ol Chemical compound OC1CCNC1 JHHZLHWJQPUNKB-UHFFFAOYSA-N 0.000 claims description 3
- FPZWZCWUIYYYBU-UHFFFAOYSA-N 2-(2-ethoxyethoxy)ethyl acetate Chemical group CCOCCOCCOC(C)=O FPZWZCWUIYYYBU-UHFFFAOYSA-N 0.000 claims description 2
- ZCUUVWCJGRQCMZ-UHFFFAOYSA-N 3-hydroxypyridin-4(1H)-one Chemical compound OC1=CC=NC=C1O ZCUUVWCJGRQCMZ-UHFFFAOYSA-N 0.000 claims description 2
- 229910019142 PO4 Inorganic materials 0.000 claims description 2
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 2
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
- CPPKAGUPTKIMNP-UHFFFAOYSA-N cyanogen fluoride Chemical compound FC#N CPPKAGUPTKIMNP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 2
- 125000001207 fluorophenyl group Chemical group 0.000 claims description 2
- 206010025135 lupus erythematosus Diseases 0.000 claims description 2
- 125000006626 methoxycarbonylamino group Chemical group 0.000 claims description 2
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 2
- 125000006405 methylpyridazinyl group Chemical group 0.000 claims description 2
- 125000002971 oxazolyl group Chemical group 0.000 claims description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 claims description 2
- 239000010452 phosphate Substances 0.000 claims description 2
- BIWOSRSKDCZIFM-UHFFFAOYSA-N piperidin-3-ol Chemical compound OC1CCCNC1 BIWOSRSKDCZIFM-UHFFFAOYSA-N 0.000 claims description 2
- PJWRJDCWSHOWTO-UHFFFAOYSA-N piperidin-3-yl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC1CCCNC1 PJWRJDCWSHOWTO-UHFFFAOYSA-N 0.000 claims description 2
- 230000001185 psoriatic effect Effects 0.000 claims description 2
- 230000003612 virological effect Effects 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims 50
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 3
- RRWIERVKMPBTBE-CVYDXHPNSA-N (3s)-1-[[(1s,3r,4s)-3-methyl-4-[methyl(7h-pyrrolo[2,3-d]pyrimidin-4-yl)amino]cyclohexyl]methylsulfonyl]piperidin-3-ol Chemical compound C([C@@H]1C[C@H]([C@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)C)S(=O)(=O)N1CCC[C@H](O)C1 RRWIERVKMPBTBE-CVYDXHPNSA-N 0.000 claims 1
- JCZPOYAMKJFOLA-ZXZARUISSA-N (3s,4r)-pyrrolidine-3,4-diol Chemical compound O[C@H]1CNC[C@H]1O JCZPOYAMKJFOLA-ZXZARUISSA-N 0.000 claims 1
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 1
- DFVBZOPVGGDURA-BZUAXINKSA-N C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCC[C@@H](O)C1 Chemical compound C([C@H]1CC[C@@H](CC1)N(C)C=1C=2C=CNC=2N=CN=1)S(=O)(=O)N1CCC[C@@H](O)C1 DFVBZOPVGGDURA-BZUAXINKSA-N 0.000 claims 1
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Classifications
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Landscapes
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| US25203909P | 2009-10-15 | 2009-10-15 | |
| PCT/IB2010/054447 WO2011045702A1 (en) | 2009-10-15 | 2010-10-01 | Pyrrolo[2,3-d] pyrimidine compounds |
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| MX2012004379A MX2012004379A (es) | 2009-10-15 | 2010-10-01 | Compuestos de pirrolo[2,3-d]pirimidina. |
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| CN102282155B (zh) | 2008-12-02 | 2017-06-09 | 日本波涛生命科学公司 | 磷原子修饰的核酸的合成方法 |
| ES2456515T3 (es) | 2009-03-23 | 2014-04-22 | Glenmark Pharmaceuticals S.A. | Derivados de pirimidindiona fusionados como moduladores de TRPA1 |
| WO2010109329A1 (en) | 2009-03-23 | 2010-09-30 | Glenmark Pharmaceuticals, S.A. | Furopyrimidinedione derivatives as trpa1 modulators |
| WO2011005761A1 (en) | 2009-07-06 | 2011-01-13 | Ontorii, Inc | Novel nucleic acid prodrugs and methods use thereof |
| TW201111385A (en) * | 2009-08-27 | 2011-04-01 | Biocryst Pharm Inc | Heterocyclic compounds as janus kinase inhibitors |
| ES2461967T3 (es) * | 2009-12-18 | 2014-05-21 | Pfizer Inc. | Compuestos de pirrolo[2,3-d]pirimidina |
| WO2012039448A1 (ja) * | 2010-09-24 | 2012-03-29 | 株式会社キラルジェン | 不斉補助基 |
| EP2734208B1 (en) | 2011-07-19 | 2017-03-01 | Wave Life Sciences Ltd. | Methods for the synthesis of functionalized nucleic acids |
| RU2632870C2 (ru) | 2011-08-12 | 2017-10-11 | Ниссан Кемикал Индастриз, Лтд. | Трициклические гетероциклические соединения и ингибиторы jak |
| CN104661664B (zh) | 2012-07-13 | 2020-07-03 | 波涛生命科学有限公司 | 手性控制 |
| AU2013288048A1 (en) | 2012-07-13 | 2015-01-22 | Wave Life Sciences Ltd. | Asymmetric auxiliary group |
| AU2013287630B2 (en) | 2012-07-13 | 2017-05-25 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant |
| HRP20180061T1 (hr) * | 2012-07-17 | 2018-02-23 | Glaxosmithkline Intellectual Property (No. 2) Limited | Indolkarbonitrili kao selektivni modulatori androgenskih receptora |
| CN103896946B (zh) * | 2012-12-28 | 2018-04-03 | 浙江导明医药科技有限公司 | 用于预防及治疗多种自身免疫疾病的新化合物 |
| EP2951590A1 (en) | 2013-02-04 | 2015-12-09 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Methods for assaying jak2 activity in red blood cells and uses thereof |
| WO2014123167A1 (ja) | 2013-02-08 | 2014-08-14 | 日産化学工業株式会社 | ３環性ピロロピリジン化合物及びｊａｋ阻害剤 |
| MA38347A1 (fr) | 2013-02-22 | 2017-10-31 | Pfizer | Dérivés de pyrrolo[2,3-d]pyrimidine en tant qu'inhibiteurs de janus kinases (jak) |
| EA028123B1 (ru) * | 2013-05-02 | 2017-10-31 | Ф. Хоффманн-Ля Рош Аг | ПРОИЗВОДНЫЕ ПИРРОЛО[2,3-d]ПИРИМИДИНА В КАЧЕСТВЕ АГОНИСТОВ РЕЦЕПТОРА CB2 |
| EP3095459A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having antitumor effect and antitumor agent |
| US10144933B2 (en) | 2014-01-15 | 2018-12-04 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having immunity induction activity, and immunity induction activator |
| EP3095460A4 (en) | 2014-01-15 | 2017-08-23 | Shin Nippon Biomedical Laboratories, Ltd. | Chiral nucleic acid adjuvant having anti-allergic activity, and anti-allergic agent |
| CN113278617A (zh) | 2014-01-16 | 2021-08-20 | 波涛生命科学有限公司 | 手性设计 |
| EP2924026A1 (en) | 2014-03-28 | 2015-09-30 | Novartis Tiergesundheit AG | Aminosulfonylmethylcyclohexanes as JAK inhibitors |
| CA2944433A1 (en) | 2014-05-14 | 2015-11-19 | Nissan Chemical Industries, Ltd. | Tricyclic compound and jak inhibitor |
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| PA8474101A1 (es) * | 1998-06-19 | 2000-09-29 | Pfizer Prod Inc | Compuestos de pirrolo [2,3-d] pirimidina |
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| EA006227B1 (ru) | 1999-12-10 | 2005-10-27 | Пфайзер Продактс Инк. | СОЕДИНЕНИЯ ПИРРОЛО[2,3-d]ПИРИМИДИНА |
| DZ3359A1 (fr) * | 2000-06-26 | 2002-01-03 | Pfizer Prod Inc | DÉRIVÉS DE PYRROLO [2,3-d] PYRIMIDINE UTILES COMME AGENTS IMMUNOSUPPRESSEURS |
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