KR20140022840A - 당뇨병을 치료하기 위한 호르몬 감수성 리파제 저해제로서의 2급-하이드록시사이클로헥실 유도체 - Google Patents
당뇨병을 치료하기 위한 호르몬 감수성 리파제 저해제로서의 2급-하이드록시사이클로헥실 유도체 Download PDFInfo
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- KR20140022840A KR20140022840A KR1020137027122A KR20137027122A KR20140022840A KR 20140022840 A KR20140022840 A KR 20140022840A KR 1020137027122 A KR1020137027122 A KR 1020137027122A KR 20137027122 A KR20137027122 A KR 20137027122A KR 20140022840 A KR20140022840 A KR 20140022840A
- Authority
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- South Korea
- Prior art keywords
- phenyl
- hydroxy
- azaspiro
- compound
- formula
- Prior art date
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- Ceased
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- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 claims abstract description 20
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- 108010055297 Sterol Esterase Proteins 0.000 claims abstract description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 6
- 201000010099 disease Diseases 0.000 claims abstract description 3
- -1 methoxy, ethoxy, n-propoxy, isopropoxy Chemical group 0.000 claims description 132
- 238000000034 method Methods 0.000 claims description 72
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- 208000008338 non-alcoholic fatty liver disease Diseases 0.000 claims description 57
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- 206010053219 non-alcoholic steatohepatitis Diseases 0.000 claims description 27
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 27
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 238000006243 chemical reaction Methods 0.000 claims description 23
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- 125000001424 substituent group Chemical group 0.000 claims description 15
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- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 13
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- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 150000002367 halogens Chemical group 0.000 claims description 10
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
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- 125000005347 halocycloalkyl group Chemical group 0.000 claims description 8
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- 125000003652 trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 8
- 125000004793 2,2,2-trifluoroethoxy group Chemical group FC(CO*)(F)F 0.000 claims description 7
- 125000005120 alkyl cycloalkyl alkyl group Chemical group 0.000 claims description 7
- 125000004858 cycloalkoxyalkyl group Chemical group 0.000 claims description 7
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- 125000004461 halocycloalkylalkyl group Chemical group 0.000 claims description 7
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- 125000002098 pyridazinyl group Chemical group 0.000 claims description 4
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- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical group CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- 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 description 3
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- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 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 description 2
- TWYXVYSMMUCKOW-UHFFFAOYSA-N 8-hydroxy-7-propan-2-yloxy-2-[4-(2,2,2-trifluoroethoxy)phenyl]-2-azaspiro[4.5]decan-1-one Chemical compound C1CC(O)C(OC(C)C)CC11C(=O)N(C=2C=CC(OCC(F)(F)F)=CC=2)CC1 TWYXVYSMMUCKOW-UHFFFAOYSA-N 0.000 claims description 2
- 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 description 2
- 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 description 2
- 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 description 2
- 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 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/54—Spiro-condensed
-
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- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
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Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
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- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
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- General Chemical & Material Sciences (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Cardiology (AREA)
- Obesity (AREA)
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- Urology & Nephrology (AREA)
- Child & Adolescent Psychology (AREA)
- Endocrinology (AREA)
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- Rheumatology (AREA)
- Gastroenterology & Hepatology (AREA)
- Emergency Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Indole Compounds (AREA)
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 (1)
| Publication Number | Publication Date |
|---|---|
| KR20140022840A true KR20140022840A (ko) | 2014-02-25 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020137027122A Ceased KR20140022840A (ko) | 2011-03-16 | 2012-03-13 | 당뇨병을 치료하기 위한 호르몬 감수성 리파제 저해제로서의 2급-하이드록시사이클로헥실 유도체 |
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
Also Published As
| Publication number | Publication date |
|---|---|
| US8722721B2 (en) | 2014-05-13 |
| CN103415506A (zh) | 2013-11-27 |
| WO2012123432A1 (en) | 2012-09-20 |
| JP2014508178A (ja) | 2014-04-03 |
| US20120238613A1 (en) | 2012-09-20 |
| RU2013142647A (ru) | 2015-04-27 |
| BR112013022416A2 (pt) | 2016-12-13 |
| MX339513B (es) | 2016-05-30 |
| HK1190706A1 (en) | 2014-07-11 |
| CA2830126A1 (en) | 2012-09-20 |
| EP2686299A1 (en) | 2014-01-22 |
| JP6117709B2 (ja) | 2017-04-19 |
| CN103415506B (zh) | 2015-08-05 |
| MX2013010006A (es) | 2013-12-06 |
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