KR20140123104A - 유비퀴틴 활성화 효소의 피라졸로피리미디닐 억제제 - Google Patents
유비퀴틴 활성화 효소의 피라졸로피리미디닐 억제제 Download PDFInfo
- Publication number
- KR20140123104A KR20140123104A KR1020147025556A KR20147025556A KR20140123104A KR 20140123104 A KR20140123104 A KR 20140123104A KR 1020147025556 A KR1020147025556 A KR 1020147025556A KR 20147025556 A KR20147025556 A KR 20147025556A KR 20140123104 A KR20140123104 A KR 20140123104A
- Authority
- KR
- South Korea
- Prior art keywords
- sulfamate
- pyrimidin
- pyrazolo
- methyl
- rac
- 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.)
- Ceased
Links
- -1 Pyrazolopyrimidinyl Chemical group 0.000 title claims description 405
- 108010091546 Ubiquitin-Activating Enzymes Proteins 0.000 title abstract description 47
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- 239000003112 inhibitor Substances 0.000 title description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 215
- 238000000034 method Methods 0.000 claims abstract description 93
- 239000000126 substance Substances 0.000 claims abstract description 70
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 46
- 206010028980 Neoplasm Diseases 0.000 claims abstract description 40
- 150000003839 salts Chemical class 0.000 claims abstract description 39
- 201000011510 cancer Diseases 0.000 claims abstract description 36
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 20
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 153
- 125000001931 aliphatic group Chemical group 0.000 claims description 118
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 102
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 100
- FIYXUOWXHWJDAM-UHFFFAOYSA-N methyl sulfamate Chemical compound COS(N)(=O)=O FIYXUOWXHWJDAM-UHFFFAOYSA-N 0.000 claims description 93
- 125000000217 alkyl group Chemical group 0.000 claims description 74
- 125000000623 heterocyclic group Chemical group 0.000 claims description 55
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- 125000001072 heteroaryl group Chemical group 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
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- 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 13
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 13
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- BREKYXZSIKAFOE-UHFFFAOYSA-N 1-[3-(trifluoromethylsulfanyl)phenyl]pyrazole Chemical compound FC(F)(F)SC1=CC=CC(=C1)N1C=CC=N1 BREKYXZSIKAFOE-UHFFFAOYSA-N 0.000 claims description 7
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- 125000001246 bromo group Chemical group Br* 0.000 claims description 5
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- ATRQECRSCHYSNP-UHFFFAOYSA-N 2-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CC=CC=N1 ATRQECRSCHYSNP-UHFFFAOYSA-N 0.000 claims 2
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- 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 1
- YIFZKLFTSGGGQW-UHFFFAOYSA-N 5-(trifluoromethyl)quinoline Chemical compound C1=CC=C2C(C(F)(F)F)=CC=CC2=N1 YIFZKLFTSGGGQW-UHFFFAOYSA-N 0.000 claims 1
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- 125000003636 chemical group Chemical group 0.000 claims 1
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- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 claims 1
- 125000005956 isoquinolyl group Chemical group 0.000 claims 1
- BNFFTDUFHKXVGG-UHFFFAOYSA-N tert-butyl 2h-pyrimidine-1-carboxylate Chemical compound CC(C)(C)OC(=O)N1CN=CC=C1 BNFFTDUFHKXVGG-UHFFFAOYSA-N 0.000 claims 1
- 230000002062 proliferating effect Effects 0.000 abstract description 6
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- A61P35/00—Antineoplastic agents
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- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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| US8008307B2 (en) | 2006-08-08 | 2011-08-30 | Millennium Pharmaceuticals, Inc. | Heteroaryl compounds useful as inhibitors of E1 activating enzymes |
| WO2013123169A1 (en) | 2012-02-17 | 2013-08-22 | Millennium Pharmaceuticals, Inc. | Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme |
| EP2879681A4 (en) | 2012-08-03 | 2015-12-23 | Millennium Pharm Inc | INDOINDUBSTITUTED PYRROLOPYRIMIDINYL HIBITORS OF UBA6 |
| JP6378759B2 (ja) | 2013-07-02 | 2018-08-22 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | Ｓｕｍｏ活性化酵素阻害剤として有用なヘテロアリール化合物 |
| JP6603712B2 (ja) | 2014-07-01 | 2019-11-06 | ミレニアム ファーマシューティカルズ， インコーポレイテッド | Ｓｕｍｏ活性化酵素の阻害薬として有用なヘテロアリール化合物 |
| JP6697453B2 (ja) * | 2014-10-29 | 2020-05-20 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | ユビキチン活性化酵素阻害物質及び放射線の投与 |
| WO2016069392A1 (en) | 2014-10-29 | 2016-05-06 | Millennium Pharmaceuticals, Inc. | Administration of ubiquitin-activating enzyme inhibitor and chemotherapeutic agents |
| JP7385658B2 (ja) | 2018-10-30 | 2023-11-22 | クロノス バイオ インコーポレイテッド | Ｃｄｋ９活性を調節するための化合物、組成物、および方法 |
| CN117412973A (zh) * | 2021-05-31 | 2024-01-16 | 上海瑛派药业有限公司 | 含氮稠合杂芳双环化合物作为usp1抑制剂及其应用 |
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| US7196092B2 (en) | 2002-09-04 | 2007-03-27 | Schering Corporation | N-heteroaryl pyrazolopyrimidines as cyclin dependent kinase inhibitors |
| MXPA05002572A (es) | 2002-09-04 | 2005-09-08 | Schering Corp | Compuestos pirazolo[1,5-a]pirimidinas como inhibidores de cinasa depentes de ciclina. |
| US7563798B2 (en) | 2002-09-04 | 2009-07-21 | Schering Corporation | Substituted pyrazolo[1,5-a]pyrimidines as protein kinase inhibitors |
| US20070179161A1 (en) | 2003-03-31 | 2007-08-02 | Vernalis (Cambridge) Limited. | Pyrazolopyrimidine compounds and their use in medicine |
| JP2005008581A (ja) | 2003-06-20 | 2005-01-13 | Kissei Pharmaceut Co Ltd | 新規なピラゾロ［１，５−ａ］ピリミジン誘導体、それを含有する医薬組成物およびそれらの用途 |
| EP1680431A1 (en) | 2003-10-17 | 2006-07-19 | Rigel Pharmaceuticals, Inc. | Benzothiazole and thiazole'5,5-b!pyridine compositions and their use as ubiquitin ligase inhibitors |
| WO2006002284A1 (en) | 2004-06-22 | 2006-01-05 | Rigel Pharmaceuticals, Inc. | Ubiquitin ligase inhibitors |
| DK1848718T3 (da) | 2005-02-04 | 2012-08-27 | Millennium Pharm Inc | E1 aktiveringsenzymhæmmere |
| US7642266B2 (en) | 2005-10-06 | 2010-01-05 | Schering Corporation | Substituted pyrazolo[1,5-a]pyrimidines as protein kinase inhibitors |
| PT1989206E (pt) * | 2006-02-02 | 2012-10-15 | Millennium Pharm Inc | Inibidores da enzima de ativação e1 |
| EP1992008A1 (en) * | 2006-02-28 | 2008-11-19 | Sez Ag | Device and method for liquid treating disc-like articles |
| US8008307B2 (en) * | 2006-08-08 | 2011-08-30 | Millennium Pharmaceuticals, Inc. | Heteroaryl compounds useful as inhibitors of E1 activating enzymes |
| BRPI0715176A8 (pt) * | 2006-08-08 | 2018-04-10 | Millennium Pharm Inc | compostos de heteroarila utéis como inibidores de enzimas de ativação e1 |
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| RU2553476C2 (ru) | 2007-08-02 | 2015-06-20 | Миллениум Фармасьютикалз, Инк. | Способ синтеза ингибиторов е1-активирующего фермента |
| US9216983B2 (en) | 2007-12-21 | 2015-12-22 | Board Of Regents, University Of Texas System | Dihydroorotate dehydrogenase inhibitors with selective anti-malarial activity |
| WO2010086040A1 (en) | 2009-01-29 | 2010-08-05 | Biomarin Iga, Ltd. | Pyrazolo-pyrimidines for treatment of duchenne muscular dystrophy |
| WO2010088518A2 (en) | 2009-01-31 | 2010-08-05 | Kalypsys, Inc. | Heterocyclic modulators of gpr119 for treatment of disease |
| SG175929A1 (en) * | 2009-05-14 | 2011-12-29 | Millennium Pharm Inc | Hydrochloride salt of ((1s,2s,4r)-4-{4-[(1s)-2,3-dihydro-1h-inden-1-ylamino]-7h-pyrrolo [2,3-d]pyrimidin-7-yl}-2-hydroxycyclopentyl)methyl sulfamate |
| AU2010347233B2 (en) | 2010-03-01 | 2015-06-18 | Oncternal Therapeutics, Inc. | Compounds for treatment of cancer |
| US20120077814A1 (en) | 2010-09-10 | 2012-03-29 | Zhong Wang | Sulfonamide, sulfamate, and sulfamothioate derivatives |
| CN103889988B (zh) | 2011-08-24 | 2018-05-04 | 米伦纽姆医药公司 | Nedd8-活化酶的抑制剂 |
| WO2013123169A1 (en) | 2012-02-17 | 2013-08-22 | Millennium Pharmaceuticals, Inc. | Pyrazolopyrimidinyl inhibitors of ubiquitin-activating enzyme |
| EP2879681A4 (en) | 2012-08-03 | 2015-12-23 | Millennium Pharm Inc | INDOINDUBSTITUTED PYRROLOPYRIMIDINYL HIBITORS OF UBA6 |
| JP6378759B2 (ja) | 2013-07-02 | 2018-08-22 | ミレニアム ファーマシューティカルズ， インコーポレイテッドＭｉｌｌｅｎｎｉｕｍ Ｐｈａｒｍａｃｅｕｔｉｃａｌｓ， Ｉｎｃ． | Ｓｕｍｏ活性化酵素阻害剤として有用なヘテロアリール化合物 |
| JP6603712B2 (ja) | 2014-07-01 | 2019-11-06 | ミレニアム ファーマシューティカルズ， インコーポレイテッド | Ｓｕｍｏ活性化酵素の阻害薬として有用なヘテロアリール化合物 |
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