CA2722326A1 - Macrocyclic compounds and their use as kinase inhibitors - Google Patents
Macrocyclic compounds and their use as kinase inhibitors Download PDFInfo
- Publication number
- CA2722326A1 CA2722326A1 CA2722326A CA2722326A CA2722326A1 CA 2722326 A1 CA2722326 A1 CA 2722326A1 CA 2722326 A CA2722326 A CA 2722326A CA 2722326 A CA2722326 A CA 2722326A CA 2722326 A1 CA2722326 A1 CA 2722326A1
- Authority
- CA
- Canada
- Prior art keywords
- chloro
- docosa
- nonaen
- tetraazatetracyclo
- pentaazatetracyclo
- 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.)
- Abandoned
Links
- 150000002678 macrocyclic compounds Chemical class 0.000 title abstract description 4
- 229940043355 kinase inhibitor Drugs 0.000 title description 2
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 2
- 150000003839 salts Chemical class 0.000 claims abstract description 138
- 150000003242 quaternary ammonium salts Chemical class 0.000 claims abstract description 81
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- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 22
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- 238000000034 method Methods 0.000 claims abstract description 11
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- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 7
- 230000002757 inflammatory effect Effects 0.000 claims abstract description 4
- 239000000203 mixture Substances 0.000 claims abstract description 4
- 229910020008 S(O) Inorganic materials 0.000 claims description 836
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 claims description 692
- 125000000217 alkyl group Chemical group 0.000 claims description 535
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 242
- 125000003118 aryl group Chemical group 0.000 claims description 225
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 192
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 184
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 178
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 169
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 163
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 163
- 150000001875 compounds Chemical class 0.000 claims description 160
- 125000001424 substituent group Chemical group 0.000 claims description 156
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- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 122
- -1 Cy1 Chemical group 0.000 claims description 117
- 125000005885 heterocycloalkylalkyl group Chemical group 0.000 claims description 112
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- 125000004663 dialkyl amino group Chemical group 0.000 claims description 49
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- 125000005083 alkoxyalkoxy group Chemical group 0.000 claims description 36
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims description 35
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- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 30
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
- 125000003282 alkyl amino group Chemical group 0.000 claims description 26
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- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 16
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- 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 12
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- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
- 208000010201 Exanthema Diseases 0.000 claims description 5
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- 125000006568 (C4-C7) heterocycloalkyl group Chemical group 0.000 claims description 4
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- AIQMFMGMTHTFLK-UHFFFAOYSA-N 6-chloro-2,4,8,15,23-pentaazatetracyclo[15.3.1.1(3,7).1(9,13)]tricosa-1(21),3(23),4,6,9(22),10,12,17,19-nonaen-14-one Chemical compound N1C(=N2)C(Cl)=CN=C2NC(C=2)=CC=CC=2CNC(=O)C2=CC=CC1=C2 AIQMFMGMTHTFLK-UHFFFAOYSA-N 0.000 claims description 3
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- 208000036824 Psoriatic arthropathy Diseases 0.000 claims description 3
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- 125000006416 CBr Chemical group BrC* 0.000 claims description 2
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- 208000001333 Colorectal Neoplasms Diseases 0.000 claims description 2
- 206010010741 Conjunctivitis Diseases 0.000 claims description 2
- 206010020751 Hypersensitivity Diseases 0.000 claims description 2
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- 208000034578 Multiple myelomas Diseases 0.000 claims description 2
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- 229910052727 yttrium Inorganic materials 0.000 claims description 2
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims 370
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims 124
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims 84
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- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 64
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims 59
- 125000001475 halogen functional group Chemical group 0.000 claims 59
- 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims 48
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims 39
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims 26
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims 20
- IVXQBCUBSIPQGU-UHFFFAOYSA-N piperazine-1-carboxamide Chemical compound NC(=O)N1CCNCC1 IVXQBCUBSIPQGU-UHFFFAOYSA-N 0.000 claims 19
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims 17
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- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims 13
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 13
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims 12
- 125000004567 azetidin-3-yl group Chemical group N1CC(C1)* 0.000 claims 12
- DPBWFNDFMCCGGJ-UHFFFAOYSA-N 4-Piperidine carboxamide Chemical compound NC(=O)C1CCNCC1 DPBWFNDFMCCGGJ-UHFFFAOYSA-N 0.000 claims 11
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 10
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims 10
- LCDCPQHFCOBUEF-UHFFFAOYSA-N pyrrolidine-1-carboxamide Chemical compound NC(=O)N1CCCC1 LCDCPQHFCOBUEF-UHFFFAOYSA-N 0.000 claims 8
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- KHBQMWCZKVMBLN-UHFFFAOYSA-N Benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC=C1 KHBQMWCZKVMBLN-UHFFFAOYSA-N 0.000 claims 6
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Applications Claiming Priority (5)
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| US4754708P | 2008-04-24 | 2008-04-24 | |
| US61/047,547 | 2008-04-24 | ||
| US12258208P | 2008-12-15 | 2008-12-15 | |
| US61/122,582 | 2008-12-15 | ||
| PCT/US2009/041555 WO2009132202A2 (en) | 2008-04-24 | 2009-04-23 | Macrocyclic compounds and their use as kinase inhibitors |
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| EP (1) | EP2274288A2 (enExample) |
| JP (1) | JP2011518836A (enExample) |
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| WO (1) | WO2009132202A2 (enExample) |
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| US8338439B2 (en) | 2008-06-27 | 2012-12-25 | Celgene Avilomics Research, Inc. | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| US11351168B1 (en) | 2008-06-27 | 2022-06-07 | Celgene Car Llc | 2,4-disubstituted pyrimidines useful as kinase inhibitors |
| TWI458721B (zh) | 2008-06-27 | 2014-11-01 | Celgene Avilomics Res Inc | 雜芳基化合物及其用途 |
| AU2013202496B2 (en) * | 2008-06-27 | 2016-08-04 | Celgene Car Llc | Heteroaryl compounds and uses thereof |
| JP5749645B2 (ja) | 2008-09-08 | 2015-07-15 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフツングＭｅｒｃｋ Ｐａｔｅｎｔ Ｇｅｓｅｌｌｓｃｈａｆｔ ｍｉｔ ｂｅｓｃｈｒａｅｎｋｔｅｒ Ｈａｆｔｕｎｇ | タンパク質キナーゼ阻害剤としての大環状ピリミジン |
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| KR101705158B1 (ko) | 2009-05-05 | 2017-02-09 | 다나-파버 캔서 인스티튜트 인크. | Ｅｇｆｒ 억제제 및 질환 치료방법 |
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| US8445490B2 (en) | 2009-10-14 | 2013-05-21 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| EP2488526B1 (en) * | 2009-10-14 | 2013-07-24 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis c |
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| EP2566872B1 (en) | 2010-05-04 | 2014-12-24 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis c |
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| WO2012019132A2 (en) | 2010-08-06 | 2012-02-09 | Cell Signaling Technology, Inc. | Anaplastic lymphoma kinase in kidney cancer |
| RU2013109393A (ru) | 2010-08-10 | 2014-09-20 | Сэлджин Авиаломикс Ресеарч, Инк. | Безилатная соль ингибитора втк |
| US8765944B2 (en) | 2010-08-19 | 2014-07-01 | Bristol-Myers Squibb Company | Compounds for the treatment of hepatitis C |
| CA2815858C (en) | 2010-11-01 | 2018-10-16 | Celgene Avilomics Research, Inc. | Heterocyclic compounds and uses thereof |
| EP2635285B1 (en) | 2010-11-01 | 2017-05-03 | Celgene Avilomics Research, Inc. | Heteroaryl compounds and uses thereof |
| CN103370076A (zh) * | 2010-11-02 | 2013-10-23 | 纽约市哥伦比亚大学托管会 | 治疗毛发脱落疾病的方法 |
| US9198911B2 (en) | 2010-11-02 | 2015-12-01 | The Trustees Of Columbia University In The City Of New York | Methods for treating hair loss disorders |
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| PL2646448T3 (pl) | 2010-11-29 | 2017-12-29 | OSI Pharmaceuticals, LLC | Makrocykliczne inhibitory kinazy |
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- 2009-04-23 EP EP09734200A patent/EP2274288A2/en not_active Withdrawn
- 2009-04-23 WO PCT/US2009/041555 patent/WO2009132202A2/en not_active Ceased
- 2009-04-23 CA CA2722326A patent/CA2722326A1/en not_active Abandoned
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| US20090286778A1 (en) | 2009-11-19 |
| WO2009132202A2 (en) | 2009-10-29 |
| JP2011518836A (ja) | 2011-06-30 |
| US8871753B2 (en) | 2014-10-28 |
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