JP6391571B2 - Atx調節剤 - Google Patents
Atx調節剤 Download PDFInfo
- Publication number
- JP6391571B2 JP6391571B2 JP2015524470A JP2015524470A JP6391571B2 JP 6391571 B2 JP6391571 B2 JP 6391571B2 JP 2015524470 A JP2015524470 A JP 2015524470A JP 2015524470 A JP2015524470 A JP 2015524470A JP 6391571 B2 JP6391571 B2 JP 6391571B2
- Authority
- JP
- Japan
- Prior art keywords
- cis
- trifluoromethyl
- naphthalen
- oxy
- carboxylic acid
- 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.)
- Expired - Fee Related
Links
- 125000000217 alkyl group Chemical group 0.000 claims description 342
- 150000001875 compounds Chemical class 0.000 claims description 218
- -1 monofluoromethyl Chemical group 0.000 claims description 198
- 229910052757 nitrogen Inorganic materials 0.000 claims description 180
- 125000000623 heterocyclic group Chemical group 0.000 claims description 115
- 229910052739 hydrogen Inorganic materials 0.000 claims description 104
- 239000001257 hydrogen Substances 0.000 claims description 104
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 87
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 75
- 125000003545 alkoxy group Chemical group 0.000 claims description 68
- NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 claims description 68
- 150000003839 salts Chemical class 0.000 claims description 66
- 125000003118 aryl group Chemical group 0.000 claims description 63
- 125000001072 heteroaryl group Chemical group 0.000 claims description 59
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 52
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 52
- 229910052799 carbon Inorganic materials 0.000 claims description 42
- 125000005347 halocycloalkyl group Chemical group 0.000 claims description 42
- 125000004452 carbocyclyl group Chemical group 0.000 claims description 40
- VZFUCHSFHOYXIS-UHFFFAOYSA-N cycloheptane carboxylic acid Natural products OC(=O)C1CCCCCC1 VZFUCHSFHOYXIS-UHFFFAOYSA-N 0.000 claims description 34
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 33
- 125000002950 monocyclic group Chemical group 0.000 claims description 33
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 29
- 201000006417 multiple sclerosis Diseases 0.000 claims description 29
- 125000004122 cyclic group Chemical group 0.000 claims description 28
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 24
- QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 23
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 23
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 22
- 125000006769 halocycloalkoxy group Chemical group 0.000 claims description 22
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 21
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 21
- 239000008194 pharmaceutical composition Substances 0.000 claims description 21
- 208000002193 Pain Diseases 0.000 claims description 20
- 206010028980 Neoplasm Diseases 0.000 claims description 17
- 241000124008 Mammalia Species 0.000 claims description 15
- 239000002253 acid Substances 0.000 claims description 15
- 238000011282 treatment Methods 0.000 claims description 15
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 12
- DMUXSGAKEXSNGN-UHFFFAOYSA-N 2-ethyloctanoic acid Chemical compound CCCCCCC(CC)C(O)=O DMUXSGAKEXSNGN-UHFFFAOYSA-N 0.000 claims description 12
- 150000001721 carbon Chemical group 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 12
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 11
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 11
- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 11
- 208000000094 Chronic Pain Diseases 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 10
- TXWOGHSRPAYOML-UHFFFAOYSA-N cyclobutanecarboxylic acid Chemical compound OC(=O)C1CCC1 TXWOGHSRPAYOML-UHFFFAOYSA-N 0.000 claims description 9
- 208000004296 neuralgia Diseases 0.000 claims description 9
- 208000021722 neuropathic pain Diseases 0.000 claims description 9
- 208000005069 pulmonary fibrosis Diseases 0.000 claims description 9
- 208000024891 symptom Diseases 0.000 claims description 9
- 206010065390 Inflammatory pain Diseases 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 8
- 208000027866 inflammatory disease Diseases 0.000 claims description 8
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 8
- 208000023275 Autoimmune disease Diseases 0.000 claims description 7
- 239000003937 drug carrier Substances 0.000 claims description 7
- 125000001188 haloalkyl group Chemical group 0.000 claims description 7
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- 239000002955 immunomodulating agent Substances 0.000 claims description 6
- 229940121354 immunomodulator Drugs 0.000 claims description 6
- SZBVQLXGZWYFCQ-UHFFFAOYSA-N 9-[8-(trifluoromethyl)-7-[4-(trifluoromethyl)cyclohexyl]oxynaphthalene-2-carbonyl]-9-azabicyclo[3.3.1]nonane-3-carboxylic acid Chemical compound C1C(C(=O)O)CC2CCCC1N2C(=O)C(C=C1C=2C(F)(F)F)=CC=C1C=CC=2OC1CCC(C(F)(F)F)CC1 SZBVQLXGZWYFCQ-UHFFFAOYSA-N 0.000 claims description 5
- QUTQICJBWHIKGL-UHFFFAOYSA-N 9-[[8-chloro-7-(4-methylcyclohexyl)oxynaphthalen-2-yl]methyl]-9-azabicyclo[3.3.1]nonane-3-carboxylic acid Chemical compound C1CC(C)CCC1OC1=CC=C(C=CC(CN2C3CCCC2CC(C3)C(O)=O)=C2)C2=C1Cl QUTQICJBWHIKGL-UHFFFAOYSA-N 0.000 claims description 5
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- FVGQYNFQNOHFPX-UEDWGHLCSA-N CC[C@H]1CC[C@H](CC1)Oc1ccc2ccc(CN3CCC(CC3)C(O)=O)cc2c1Cl Chemical compound CC[C@H]1CC[C@H](CC1)Oc1ccc2ccc(CN3CCC(CC3)C(O)=O)cc2c1Cl FVGQYNFQNOHFPX-UEDWGHLCSA-N 0.000 claims description 5
- GRJRKAIUGAAAKL-DFVIVQSZSA-N ClC=1C(=CC=C2C=CC(=CC12)C(C)N1CCC(CC1)C(=O)O)O[C@@H]1CC[C@@H](CC1)C(F)(F)F Chemical compound ClC=1C(=CC=C2C=CC(=CC12)C(C)N1CCC(CC1)C(=O)O)O[C@@H]1CC[C@@H](CC1)C(F)(F)F GRJRKAIUGAAAKL-DFVIVQSZSA-N 0.000 claims description 5
- DRNZZVUIAKJEJG-KDURUIRLSA-N FC(C=1C(=CC=C2C=CC(=CC12)CN1CCC(CC1)C(=O)O)O[C@@H]1CC[C@@H](CC1)C(F)(F)F)(F)F Chemical compound FC(C=1C(=CC=C2C=CC(=CC12)CN1CCC(CC1)C(=O)O)O[C@@H]1CC[C@@H](CC1)C(F)(F)F)(F)F DRNZZVUIAKJEJG-KDURUIRLSA-N 0.000 claims description 5
- RZPPKCWFXKPGOK-XBZZPOKOSA-N OC(=O)C1CC2CCCC(C1)N2Cc1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(c2c1)C(F)(F)F Chemical compound OC(=O)C1CC2CCCC(C1)N2Cc1ccc2ccc(O[C@H]3CC[C@H](CC3)C(F)(F)F)c(c2c1)C(F)(F)F RZPPKCWFXKPGOK-XBZZPOKOSA-N 0.000 claims description 5
- DASZWTMGJQVNFR-BGYRXZFFSA-N OC(=O)C1CCN(Cc2ccc3ccc(O[C@H]4CC[C@H](CC4)C(F)(F)F)c(C#N)c3c2)CC1 Chemical compound OC(=O)C1CCN(Cc2ccc3ccc(O[C@H]4CC[C@H](CC4)C(F)(F)F)c(C#N)c3c2)CC1 DASZWTMGJQVNFR-BGYRXZFFSA-N 0.000 claims description 5
- KTQSEQDZGRAAHL-AHRSYUTCSA-N OC(=O)C[C@H]1CCCN(Cc2ccc3ccc(O[C@H]4CC[C@H](CC4)C(F)(F)F)c(c3c2)C(F)(F)F)C1 Chemical compound OC(=O)C[C@H]1CCCN(Cc2ccc3ccc(O[C@H]4CC[C@H](CC4)C(F)(F)F)c(c3c2)C(F)(F)F)C1 KTQSEQDZGRAAHL-AHRSYUTCSA-N 0.000 claims description 5
- SRJOCJYGOFTFLH-UHFFFAOYSA-N isonipecotic acid Chemical compound OC(=O)C1CCNCC1 SRJOCJYGOFTFLH-UHFFFAOYSA-N 0.000 claims description 5
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- 230000002265 prevention Effects 0.000 claims description 5
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Classifications
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- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D211/36—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D223/06—Heterocyclic compounds containing seven-membered rings having one nitrogen atom as the only ring hetero atom not condensed with other rings with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
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- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- C—CHEMISTRY; METALLURGY
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- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/08—Bridged systems
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- C07C2602/42—Systems containing two condensed rings the rings having more than two atoms in common the bicyclo ring system containing seven carbon atoms
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
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| IN2014DN09346A (https=) | 2012-06-13 | 2015-07-17 | Hoffmann La Roche | |
| EA027809B1 (ru) | 2012-07-27 | 2017-09-29 | Биоген Айдек Ма Инк. | Соединения, которые являются s1p-модулирующими агентами и/или atx-модулирующими агентами |
| US9555050B2 (en) | 2012-07-27 | 2017-01-31 | Biogen Ma Inc. | ATX modulating agents |
| WO2014025709A1 (en) | 2012-08-06 | 2014-02-13 | Biogen Idec Ma Inc. | Compounds that are s1p modulating agents and/or atx modulating agents |
| WO2014025708A1 (en) | 2012-08-06 | 2014-02-13 | Biogen Idec Ma Inc. | Compounds that are s1p modulating agents and/or atx modulating agents |
| KR102179599B1 (ko) | 2012-09-25 | 2020-11-19 | 에프. 호프만-라 로슈 아게 | 이환형 유도체 |
| AR095079A1 (es) | 2013-03-12 | 2015-09-16 | Hoffmann La Roche | Derivados de octahidro-pirrolo[3,4-c]-pirrol y piridina-fenilo |
| CN105764905B (zh) | 2013-11-26 | 2019-06-07 | 豪夫迈·罗氏有限公司 | 新的八氢-环丁二烯并[1,2-c;3,4-c’]二吡咯-2基 |
| CN106103446B (zh) | 2014-03-26 | 2019-07-30 | 豪夫迈·罗氏有限公司 | 作为自分泌运动因子(atx)和溶血磷脂酸(lpa)生产抑制剂的二环化合物 |
| WO2015144609A1 (en) | 2014-03-26 | 2015-10-01 | F. Hoffmann-La Roche Ag | Condensed [1,4]diazepine compounds as autotaxin (atx) and lysophosphatidic acid (lpa) production inhibitors |
| GB201501870D0 (en) | 2015-02-04 | 2015-03-18 | Cancer Rec Tech Ltd | Autotaxin inhibitors |
| GB201502020D0 (en) | 2015-02-06 | 2015-03-25 | Cancer Rec Tech Ltd | Autotaxin inhibitory compounds |
| MA41898A (fr) | 2015-04-10 | 2018-02-13 | Hoffmann La Roche | Dérivés de quinazolinone bicyclique |
| AU2016270373A1 (en) | 2015-06-05 | 2018-01-04 | Vertex Pharmaceuticals Incorporated | Triazoles for the treatment of demyelinating diseases |
| CA2992889A1 (en) | 2015-09-04 | 2017-03-09 | F. Hoffmann-La Roche Ag | Phenoxymethyl derivatives |
| RU2018112230A (ru) | 2015-09-24 | 2019-10-30 | Ф. Хоффманн-Ля Рош Аг | Бициклические соединения в качестве ингибиторов atx |
| CR20180057A (es) | 2015-09-24 | 2018-04-02 | Hoffmann La Roche | Nuevos compuestos biciclicos como inhibidores duales de atx/ca. |
| KR20180054830A (ko) | 2015-09-24 | 2018-05-24 | 에프. 호프만-라 로슈 아게 | 오토탁신(atx) 억제제로서의 이환형 화합물 |
| AU2016328365B2 (en) | 2015-09-24 | 2020-04-23 | F. Hoffmann-La Roche Ag | New bicyclic compounds as dual ATX/CA inhibitors |
| WO2018106646A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Aminotriazoles for the treatment of demyelinating diseases |
| WO2018106641A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Pyrazoles for the treatment of demyelinating diseases |
| WO2018106643A1 (en) | 2016-12-06 | 2018-06-14 | Vertex Pharmaceuticals Incorporated | Heterocyclic azoles for the treatment of demyelinating diseases |
| SG11201908560SA (en) | 2017-03-16 | 2019-10-30 | Hoffmann La Roche | Heterocyclic compounds useful as dual atx/ca inhibitors |
| WO2018167113A1 (en) | 2017-03-16 | 2018-09-20 | F. Hoffmann-La Roche Ag | New bicyclic compounds as atx inhibitors |
| EP3638672A1 (en) | 2017-06-13 | 2020-04-22 | GlaxoSmithKline Intellectual Property Development Limited | Chemical compounds as h-pgds inhibitors |
| WO2020156459A1 (zh) | 2019-02-01 | 2020-08-06 | 湖北生物医药产业技术研究院有限公司 | 吡咯并嘧啶衍生物及其用途 |
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| UA113507C2 (xx) * | 2011-02-07 | 2017-02-10 | Модулятори s1p | |
| WO2012107500A1 (en) * | 2011-02-10 | 2012-08-16 | Novartis Ag | [1, 2, 4] triazolo [4, 3 -b] pyridazine compounds as inhibitors of the c-met tyrosine kinase |
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| MX363388B (es) * | 2012-07-27 | 2019-03-20 | Biogen Ma Inc | Agentes moduladores de autotaxina. |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2018135379A (ja) * | 2012-07-27 | 2018-08-30 | バイオジェン・エムエイ・インコーポレイテッドBiogen MA Inc. | Atx調節剤 |
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