TW201100429A - N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors - Google Patents
N-(hetero)aryl-pyrrolidine derivatives of pyrazol-4-yl-pyrrolo[2,3-d]pyrimidines and pyrrol-3-yl-pyrrolo[2,3-d]pyrimidines as janus kinase inhibitors Download PDFInfo
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- TW201100429A TW201100429A TW099116419A TW99116419A TW201100429A TW 201100429 A TW201100429 A TW 201100429A TW 099116419 A TW099116419 A TW 099116419A TW 99116419 A TW99116419 A TW 99116419A TW 201100429 A TW201100429 A TW 201100429A
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- alkyl
- pyrrolo
- ring
- pyridine
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- 229940122245 Janus kinase inhibitor Drugs 0.000 title abstract description 18
- PSJGZWCZKPCRFZ-UHFFFAOYSA-N 2-(1h-pyrrol-3-yl)-7h-pyrrolo[2,3-d]pyrimidine Chemical class N1C2=NC=CC2=CN=C1C=1C=CNC=1 PSJGZWCZKPCRFZ-UHFFFAOYSA-N 0.000 title 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 62
- 201000010099 disease Diseases 0.000 claims abstract description 57
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 31
- 201000011510 cancer Diseases 0.000 claims abstract description 22
- 238000011282 treatment Methods 0.000 claims abstract description 17
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 12
- 208000027866 inflammatory disease Diseases 0.000 claims abstract description 12
- -1 nitro, hydroxy Chemical group 0.000 claims description 299
- 125000000217 alkyl group Chemical group 0.000 claims description 279
- 239000002585 base Substances 0.000 claims description 245
- 150000001875 compounds Chemical class 0.000 claims description 234
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 claims description 172
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 152
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 143
- 150000003839 salts Chemical class 0.000 claims description 121
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 116
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 108
- 125000001153 fluoro group Chemical group F* 0.000 claims description 101
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 96
- 125000001072 heteroaryl group Chemical group 0.000 claims description 83
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 73
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 71
- 229910052739 hydrogen Inorganic materials 0.000 claims description 61
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 58
- 239000000126 substance Substances 0.000 claims description 58
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 57
- 239000001257 hydrogen Substances 0.000 claims description 57
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 55
- UJOBWOGCFQCDNV-UHFFFAOYSA-N 9H-carbazole Chemical compound C1=CC=C2C3=CC=CC=C3NC2=C1 UJOBWOGCFQCDNV-UHFFFAOYSA-N 0.000 claims description 51
- 150000001204 N-oxides Chemical class 0.000 claims description 51
- 125000003545 alkoxy group Chemical group 0.000 claims description 51
- 238000000034 method Methods 0.000 claims description 50
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 48
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 46
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 41
- 125000003118 aryl group Chemical group 0.000 claims description 39
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 37
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 36
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- 150000001412 amines Chemical class 0.000 claims description 33
- 125000003277 amino group Chemical group 0.000 claims description 32
- 239000002253 acid Substances 0.000 claims description 30
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- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims description 29
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- 125000003282 alkyl amino group Chemical group 0.000 claims description 28
- 125000004429 atom Chemical group 0.000 claims description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims description 27
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- 102100033438 Tyrosine-protein kinase JAK1 Human genes 0.000 claims description 17
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- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 10
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- JUJWROOIHBZHMG-UHFFFAOYSA-O pyridinium Chemical compound C1=CC=[NH+]C=C1 JUJWROOIHBZHMG-UHFFFAOYSA-O 0.000 claims description 8
- 239000002689 soil Substances 0.000 claims description 8
- JJTNLWSCFYERCK-UHFFFAOYSA-N 7h-pyrrolo[2,3-d]pyrimidine Chemical group N1=CN=C2NC=CC2=C1 JJTNLWSCFYERCK-UHFFFAOYSA-N 0.000 claims description 7
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 7
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| US18062209P | 2009-05-22 | 2009-05-22 | |
| US22509209P | 2009-07-13 | 2009-07-13 |
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| MY156727A (en) | 2016-03-15 |
| CN102458581A (zh) | 2012-05-16 |
| MX2011012353A (es) | 2011-12-14 |
| SG176130A1 (en) | 2011-12-29 |
| EA025520B1 (ru) | 2017-01-30 |
| ES2487542T3 (es) | 2014-08-21 |
| CA2762174A1 (en) | 2010-11-25 |
| EA201171454A1 (ru) | 2012-06-29 |
| US20100298334A1 (en) | 2010-11-25 |
| WO2010135650A1 (en) | 2010-11-25 |
| CL2011002956A1 (es) | 2012-05-25 |
| CO6440524A2 (es) | 2012-05-15 |
| CN102458581B (zh) | 2016-03-30 |
| AU2010249380A1 (en) | 2011-12-08 |
| IL216463A0 (en) | 2012-02-29 |
| EP2432555A1 (en) | 2012-03-28 |
| NZ596479A (en) | 2014-01-31 |
| US8716303B2 (en) | 2014-05-06 |
| US9334274B2 (en) | 2016-05-10 |
| KR101771401B1 (ko) | 2017-08-25 |
| JP2012527483A (ja) | 2012-11-08 |
| AR076794A1 (es) | 2011-07-06 |
| BRPI1012159A2 (pt) | 2020-09-15 |
| KR20120034665A (ko) | 2012-04-12 |
| AU2010249380B2 (en) | 2015-08-20 |
| IL216463A (en) | 2017-09-28 |
| BRPI1012159B1 (pt) | 2022-01-25 |
| JP5775070B2 (ja) | 2015-09-09 |
| CA2762174C (en) | 2018-02-20 |
| EP2432555B1 (en) | 2014-04-30 |
| ZA201108544B (en) | 2013-04-24 |
| CR20110620A (es) | 2012-02-02 |
| US20140221379A1 (en) | 2014-08-07 |
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