JP2014508178A5 - - Google Patents
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- Publication number
- JP2014508178A5 JP2014508178A5 JP2013558403A JP2013558403A JP2014508178A5 JP 2014508178 A5 JP2014508178 A5 JP 2014508178A5 JP 2013558403 A JP2013558403 A JP 2013558403A JP 2013558403 A JP2013558403 A JP 2013558403A JP 2014508178 A5 JP2014508178 A5 JP 2014508178A5
- Authority
- JP
- Japan
- Prior art keywords
- compound according
- phenyl
- hydroxy
- prevention
- treatment
- 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.)
- Granted
Links
- 150000001875 compounds Chemical class 0.000 claims 47
- 230000002265 prevention Effects 0.000 claims 25
- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims 24
- 125000000217 alkyl group Chemical group 0.000 claims 12
- 206010012601 diabetes mellitus Diseases 0.000 claims 12
- -1 methoxy, ethoxy, n-propoxy, isopropoxy, trifluoromethoxy, trifluoroethoxy Chemical group 0.000 claims 12
- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 12
- 125000004438 haloalkoxy group Chemical group 0.000 claims 11
- 238000000034 method Methods 0.000 claims 9
- 201000001320 Atherosclerosis Diseases 0.000 claims 8
- 208000024172 Cardiovascular disease Diseases 0.000 claims 8
- 208000032928 Dyslipidaemia Diseases 0.000 claims 8
- 206010061218 Inflammation Diseases 0.000 claims 8
- 208000017170 Lipid metabolism disease Diseases 0.000 claims 8
- 208000001145 Metabolic Syndrome Diseases 0.000 claims 8
- 208000008589 Obesity Diseases 0.000 claims 8
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims 8
- 125000003545 alkoxy group Chemical group 0.000 claims 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims 8
- 230000004064 dysfunction Effects 0.000 claims 8
- 230000004054 inflammatory process Effects 0.000 claims 8
- 230000002107 myocardial effect Effects 0.000 claims 8
- 235000020824 obesity Nutrition 0.000 claims 8
- 125000001188 haloalkyl group Chemical group 0.000 claims 7
- 125000001424 substituent group Chemical group 0.000 claims 7
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims 6
- 229910052739 hydrogen Inorganic materials 0.000 claims 6
- 239000001257 hydrogen Substances 0.000 claims 6
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims 5
- 239000003814 drug Substances 0.000 claims 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims 4
- 229910052736 halogen Inorganic materials 0.000 claims 4
- 150000002367 halogens Chemical class 0.000 claims 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 4
- 208000001072 type 2 diabetes mellitus Diseases 0.000 claims 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 3
- 125000000000 cycloalkoxy group Chemical group 0.000 claims 3
- 150000002431 hydrogen Chemical class 0.000 claims 3
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims 3
- PPWLUVUZMIXMJC-DZKIICNBSA-N (5s,7s,8s)-8-hydroxy-7-(2,2,2-trifluoroethoxy)-2-[4-(trifluoromethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1[C@H](OCC(F)(F)F)[C@@H](O)CC[C@@]11C(=O)N(C=2C=CC(OC(F)(F)F)=CC=2)CC1 PPWLUVUZMIXMJC-DZKIICNBSA-N 0.000 claims 2
- YZTKPBAXESIKIE-CUSZFKRNSA-N (5s,7s,8s)-8-hydroxy-7-(2,2,2-trifluoroethoxy)-2-[4-[(1r)-2,2,2-trifluoro-1-methoxyethyl]phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1=CC([C@@H](OC)C(F)(F)F)=CC=C1N1C(=O)[C@]2(C[C@@H]([C@@H](O)CC2)OCC(F)(F)F)CC1 YZTKPBAXESIKIE-CUSZFKRNSA-N 0.000 claims 2
- BGHKCNHEBSHENM-UHFFFAOYSA-N 8-hydroxy-7-propan-2-yl-2-[4-(2,2,2-trifluoroethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1CC(O)C(C(C)C)CC11C(=O)N(C=2C=CC(OCC(F)(F)F)=CC=2)CC1 BGHKCNHEBSHENM-UHFFFAOYSA-N 0.000 claims 2
- NLHHYKJVMWXELZ-UHFFFAOYSA-N 8-hydroxy-7-propan-2-yl-2-[4-(trifluoromethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1CC(O)C(C(C)C)CC11C(=O)N(C=2C=CC(OC(F)(F)F)=CC=2)CC1 NLHHYKJVMWXELZ-UHFFFAOYSA-N 0.000 claims 2
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical group [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims 2
- 125000005120 alkyl cycloalkyl alkyl group Chemical group 0.000 claims 2
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 claims 2
- 125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- 125000004994 halo alkoxy alkyl group Chemical group 0.000 claims 2
- 125000006769 halocycloalkoxy group Chemical group 0.000 claims 2
- 125000005347 halocycloalkyl group Chemical group 0.000 claims 2
- 125000004461 halocycloalkylalkyl group Chemical group 0.000 claims 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims 2
- 125000002098 pyridazinyl group Chemical group 0.000 claims 2
- 125000004076 pyridyl group Chemical group 0.000 claims 2
- 125000000714 pyrimidinyl group Chemical group 0.000 claims 2
- PPWLUVUZMIXMJC-IIAWOOMASA-N (5r,7r,8r)-8-hydroxy-7-(2,2,2-trifluoroethoxy)-2-[4-(trifluoromethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1[C@@H](OCC(F)(F)F)[C@H](O)CC[C@]11C(=O)N(C=2C=CC(OC(F)(F)F)=CC=2)CC1 PPWLUVUZMIXMJC-IIAWOOMASA-N 0.000 claims 1
- IJQQUSSCHHFEGJ-MPTYRVRUSA-N (5s,7s,8s)-8-hydroxy-7-(2,2,2-trifluoroethoxy)-2-[4-[(1r)-2,2,2-trifluoro-1-hydroxyethyl]phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1=CC([C@@H](O)C(F)(F)F)=CC=C1N1C(=O)[C@]2(C[C@@H]([C@@H](O)CC2)OCC(F)(F)F)CC1 IJQQUSSCHHFEGJ-MPTYRVRUSA-N 0.000 claims 1
- SYPRGLCEKGZXFH-YCSHWKNNSA-N (5s,7s,8s)-8-hydroxy-7-(2,2,2-trifluoroethoxy)-2-[4-[(1r)-2,2,2-trifluoro-1-phenylmethoxyethyl]phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1[C@H](OCC(F)(F)F)[C@@H](O)CC[C@@]11C(=O)N(C=2C=CC(=CC=2)[C@@H](OCC=2C=CC=CC=2)C(F)(F)F)CC1 SYPRGLCEKGZXFH-YCSHWKNNSA-N 0.000 claims 1
- UISKTUYIECGCNM-GNBUJSLZSA-N (5s,7s,8s)-8-hydroxy-7-propan-2-yloxy-2-[4-[(1r)-2,2,2-trifluoro-1-methoxyethyl]phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1=CC([C@@H](OC)C(F)(F)F)=CC=C1N1C(=O)[C@]2(C[C@@H]([C@@H](O)CC2)OC(C)C)CC1 UISKTUYIECGCNM-GNBUJSLZSA-N 0.000 claims 1
- 125000004863 4-trifluoromethoxyphenyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C([H])C([H])=C1* 0.000 claims 1
- DHPMSQPFKXIQSS-UHFFFAOYSA-N 7-ethoxy-8-hydroxy-2-[4-(2,2,2-trifluoroethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1CC(O)C(OCC)CC11C(=O)N(C=2C=CC(OCC(F)(F)F)=CC=2)CC1 DHPMSQPFKXIQSS-UHFFFAOYSA-N 0.000 claims 1
- JNJPMTLZSXBHIJ-UHFFFAOYSA-N 7-ethoxy-8-hydroxy-2-[4-(trifluoromethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1CC(O)C(OCC)CC11C(=O)N(C=2C=CC(OC(F)(F)F)=CC=2)CC1 JNJPMTLZSXBHIJ-UHFFFAOYSA-N 0.000 claims 1
- ZYNDZSWTZGGJGC-UHFFFAOYSA-N 8-hydroxy-7-(2,2,2-trifluoroethoxy)-2-[4-(2,2,2-trifluoroethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1C(OCC(F)(F)F)C(O)CCC11C(=O)N(C=2C=CC(OCC(F)(F)F)=CC=2)CC1 ZYNDZSWTZGGJGC-UHFFFAOYSA-N 0.000 claims 1
- PPWLUVUZMIXMJC-UHFFFAOYSA-N 8-hydroxy-7-(2,2,2-trifluoroethoxy)-2-[4-(trifluoromethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1C(OCC(F)(F)F)C(O)CCC11C(=O)N(C=2C=CC(OC(F)(F)F)=CC=2)CC1 PPWLUVUZMIXMJC-UHFFFAOYSA-N 0.000 claims 1
- SUYFLKVYVRWKMI-UHFFFAOYSA-N 8-hydroxy-7-methoxy-2-[4-(trifluoromethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1CC(O)C(OC)CC11C(=O)N(C=2C=CC(OC(F)(F)F)=CC=2)CC1 SUYFLKVYVRWKMI-UHFFFAOYSA-N 0.000 claims 1
- HNTWSIJLQIMPBZ-UHFFFAOYSA-N 8-hydroxy-7-propan-2-yloxy-2-[4-(trifluoromethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1CC(O)C(OC(C)C)CC11C(=O)N(C=2C=CC(OC(F)(F)F)=CC=2)CC1 HNTWSIJLQIMPBZ-UHFFFAOYSA-N 0.000 claims 1
- PTGRKADUKRSWIA-UHFFFAOYSA-N 8-hydroxy-7-propoxy-2-[4-(trifluoromethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1CC(O)C(OCCC)CC11C(=O)N(C=2C=CC(OC(F)(F)F)=CC=2)CC1 PTGRKADUKRSWIA-UHFFFAOYSA-N 0.000 claims 1
- QGVFVHFQCBELNT-UHFFFAOYSA-N 8-hydroxy-7-propyl-2-[4-(2,2,2-trifluoroethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1CC(O)C(CCC)CC11C(=O)N(C=2C=CC(OCC(F)(F)F)=CC=2)CC1 QGVFVHFQCBELNT-UHFFFAOYSA-N 0.000 claims 1
- CRLYLLMVSJJPLT-UHFFFAOYSA-N 8-hydroxy-7-propyl-2-[4-(trifluoromethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1CC(O)C(CCC)CC11C(=O)N(C=2C=CC(OC(F)(F)F)=CC=2)CC1 CRLYLLMVSJJPLT-UHFFFAOYSA-N 0.000 claims 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical group CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims 1
- 102000000019 Sterol Esterase Human genes 0.000 claims 1
- 108010055297 Sterol Esterase Proteins 0.000 claims 1
- 239000013543 active substance Substances 0.000 claims 1
- 239000003638 chemical reducing agent Substances 0.000 claims 1
- 201000010099 disease Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
- 229910052744 lithium Inorganic materials 0.000 claims 1
- OTCKOJUMXQWKQG-UHFFFAOYSA-L magnesium bromide Chemical compound [Mg+2].[Br-].[Br-] OTCKOJUMXQWKQG-UHFFFAOYSA-L 0.000 claims 1
- 229910001623 magnesium bromide Inorganic materials 0.000 claims 1
- 229910001629 magnesium chloride Inorganic materials 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000008194 pharmaceutical composition Substances 0.000 claims 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims 1
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11158386 | 2011-03-16 | ||
| EP11158386.0 | 2011-03-16 | ||
| PCT/EP2012/054307 WO2012123432A1 (en) | 2011-03-16 | 2012-03-13 | Sec-hydroxycyclohexyl derivatives as hsl inhibitors for the treatment diabetes |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2014508178A JP2014508178A (ja) | 2014-04-03 |
| JP2014508178A5 true JP2014508178A5 (enExample) | 2015-05-07 |
| JP6117709B2 JP6117709B2 (ja) | 2017-04-19 |
Family
ID=45812793
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2013558403A Active JP6117709B2 (ja) | 2011-03-16 | 2012-03-13 | 糖尿病治療のためのｈｓｌ阻害剤としてのｓｅｃ−ヒドロキシシクロヘキシル誘導体 |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US8722721B2 (enExample) |
| EP (1) | EP2686299A1 (enExample) |
| JP (1) | JP6117709B2 (enExample) |
| KR (1) | KR20140022840A (enExample) |
| CN (1) | CN103415506B (enExample) |
| BR (1) | BR112013022416A2 (enExample) |
| CA (1) | CA2830126A1 (enExample) |
| MX (1) | MX339513B (enExample) |
| RU (1) | RU2013142647A (enExample) |
| WO (1) | WO2012123432A1 (enExample) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US8097634B2 (en) * | 2010-04-15 | 2012-01-17 | Hoffmann-La Roche Inc. | Azacyclic derivatives |
| US8809384B2 (en) * | 2011-03-25 | 2014-08-19 | Hoffmann-La Roche Inc. | Azaspirodecanone compounds |
| UY36060A (es) | 2014-04-02 | 2015-10-30 | Bayer Pharma AG | Compuestos de azol sustituidos con amida |
| CN104788360B (zh) * | 2015-03-30 | 2017-07-25 | 曲阜师范大学 | 3‑砜基螺环三烯酮类化合物及其制备方法 |
| CN117551046B (zh) * | 2023-11-17 | 2025-10-28 | 广东药科大学附属第一医院 | 二氨基脲类hsl抑制剂、制备方法及其用途 |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE10247680B4 (de) * | 2002-10-12 | 2005-09-01 | Aventis Pharma Deutschland Gmbh | Neue bicyclische Inhibitoren der Hormon Sensitiven Lipase |
| EP1529528A1 (en) * | 2003-11-07 | 2005-05-11 | Universitätsklinikum Freiburg | 2-pyrrolidone derivatives and their use in protecting mammalian cells against oxidation stress |
| WO2007103719A2 (en) * | 2006-03-03 | 2007-09-13 | Incyte Corporation | MODULATORS OF 11-β HYDROXYL STEROID DEHYDROGENASE TYPE 1, PHARMACEUTICAL COMPOSITIONS THEREOF, AND METHODS OF USING THE SAME |
| DK2035379T3 (da) * | 2006-04-25 | 2010-09-06 | Lilly Co Eli | Inhibitorer af 11-beta-hydroxysteroiddehydrogenase 1 |
| US8329904B2 (en) * | 2009-05-12 | 2012-12-11 | Hoffmann-La Roche Inc. | Azacyclic derivatives |
| US8440710B2 (en) | 2009-10-15 | 2013-05-14 | Hoffmann-La Roche Inc. | HSL inhibitors useful in the treatment of diabetes |
| TW201118069A (en) * | 2009-10-28 | 2011-06-01 | Lundbeck & Co As H | Spirolactam derivatives and uses of same |
| US8389539B2 (en) * | 2009-12-01 | 2013-03-05 | Hoffman-La Roche Inc. | Azacyclic derivatives |
| US8097634B2 (en) * | 2010-04-15 | 2012-01-17 | Hoffmann-La Roche Inc. | Azacyclic derivatives |
| WO2011143163A1 (en) | 2010-05-11 | 2011-11-17 | Sanofi | Substituted n-phenyl spirolactam bipyrrolidines, preparation and therapeutic use thereof |
-
2012
- 2012-03-08 US US13/414,753 patent/US8722721B2/en not_active Expired - Fee Related
- 2012-03-13 EP EP12708036.4A patent/EP2686299A1/en not_active Withdrawn
- 2012-03-13 KR KR1020137027122A patent/KR20140022840A/ko not_active Ceased
- 2012-03-13 JP JP2013558403A patent/JP6117709B2/ja active Active
- 2012-03-13 MX MX2013010006A patent/MX339513B/es active IP Right Grant
- 2012-03-13 CA CA2830126A patent/CA2830126A1/en not_active Abandoned
- 2012-03-13 WO PCT/EP2012/054307 patent/WO2012123432A1/en not_active Ceased
- 2012-03-13 RU RU2013142647/04A patent/RU2013142647A/ru not_active Application Discontinuation
- 2012-03-13 CN CN201280012084.XA patent/CN103415506B/zh not_active Expired - Fee Related
- 2012-03-13 BR BR112013022416A patent/BR112013022416A2/pt not_active IP Right Cessation
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