MA30686B1 - Inhibiteurs de la 11-beta-hydroxysteroide deshydrogenase. - Google Patents

Inhibiteurs de la 11-beta-hydroxysteroide deshydrogenase.

Info

Publication number
MA30686B1
MA30686B1 MA31398A MA31398A MA30686B1 MA 30686 B1 MA30686 B1 MA 30686B1 MA 31398 A MA31398 A MA 31398A MA 31398 A MA31398 A MA 31398A MA 30686 B1 MA30686 B1 MA 30686B1
Authority
MA
Morocco
Prior art keywords
inhibitors
beta
compounds
hydroxysteroid dehydrogenase
hsd
Prior art date
Application number
MA31398A
Other languages
English (en)
Inventor
Julie Kay Bush
Marvin Martin Hansen
Renhua Li
Thomas Edward Mabry
Nancy June Snyder
Owen Brendan Wallace
Yanping Xu
Original Assignee
Lilly Co Eli
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=38564359&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=MA30686(B1) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by Lilly Co Eli filed Critical Lilly Co Eli
Publication of MA30686B1 publication Critical patent/MA30686B1/fr

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/12Heterocyclic 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 chain containing hetero atoms as chain links
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/46Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
    • C07D207/50Nitrogen atoms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40Heterocyclic 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
    • A61K31/4015Heterocyclic 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 having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00Drugs for disorders of the metabolism
    • A61P3/08Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D207/00Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D207/24Oxygen or sulfur atoms
    • C07D207/262-Pyrrolidones
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/02Heterocyclic 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
    • C07D401/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D401/00Heterocyclic 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
    • C07D401/14Heterocyclic 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 three or more hetero rings

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Diabetes (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Steroid Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Enzymes And Modification Thereof (AREA)

Abstract

LA PRÉSENTE INVENTION CONCERNE DE NOUVEAUX COMPOSÉS REPRÉSENTÉS PAR LA FORMULE 1: (1) POSSÉDANT UNE ACTIVITÉ ANTAGONISTE 1 DE TYPE 11-HSD, AINSI QUE DES PROCÉDÉS DE PRÉPARATION DE CES COMPOSÉS. DANS UN AUTRE MODE DE RÉALISATION, L'INVENTION CONCERNE DES COMPOSITIONS PHARMACEUTIQUES COMPRENANT DES COMPOSÉS REPRÉSENTÉS PAR LA FORMULE 1, AINSI QUE DES PROCÉDÉ D'UTILISATION DE CES COMPOSÉS ET DE CES COMPOSITIONS POUR TRAITER LE DIABÈTE, L'HYPERGLYCÉMIE, L'OBÉSITÉ, L'HYPERTENSION, L'HYPERLIPIDÉMIE. LE SYNDROME MÉTABOLIQUE ET D'AUTRES ÉTATS ASSOCIÉS À L'ACTIVITÉ 1 DE TYPE 11-HSD.
MA31398A 2006-04-24 2008-11-20 Inhibiteurs de la 11-beta-hydroxysteroide deshydrogenase. MA30686B1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US74547506P 2006-04-24 2006-04-24

Publications (1)

Publication Number Publication Date
MA30686B1 true MA30686B1 (fr) 2009-09-01

Family

ID=38564359

Family Applications (1)

Application Number Title Priority Date Filing Date
MA31398A MA30686B1 (fr) 2006-04-24 2008-11-20 Inhibiteurs de la 11-beta-hydroxysteroide deshydrogenase.

Country Status (32)

Country Link
US (1) US8153807B2 (fr)
EP (1) EP2021336B1 (fr)
JP (1) JP5269765B2 (fr)
KR (1) KR101059614B1 (fr)
CN (1) CN101432275B (fr)
AT (1) ATE472542T1 (fr)
AU (1) AU2007244955B2 (fr)
BR (1) BRPI0710467A2 (fr)
CA (1) CA2646624C (fr)
CO (1) CO6140034A2 (fr)
CR (2) CR10402A (fr)
CY (1) CY1110753T1 (fr)
DE (1) DE602007007473D1 (fr)
DK (1) DK2021336T3 (fr)
EA (1) EA015106B1 (fr)
EC (1) ECSP088833A (fr)
ES (1) ES2345792T3 (fr)
HR (1) HRP20100397T1 (fr)
IL (1) IL194810A (fr)
MA (1) MA30686B1 (fr)
MX (1) MX2008013649A (fr)
MY (1) MY148079A (fr)
NO (1) NO20084318L (fr)
NZ (1) NZ571176A (fr)
PL (1) PL2021336T3 (fr)
PT (1) PT2021336E (fr)
RS (1) RS51450B (fr)
SI (1) SI2021336T1 (fr)
TN (1) TNSN08417A1 (fr)
UA (1) UA94741C2 (fr)
WO (1) WO2007127688A2 (fr)
ZA (1) ZA200808687B (fr)

Families Citing this family (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EA014718B1 (ru) * 2006-04-21 2011-02-28 Эли Лилли Энд Компани Производные бифениламидлактама в качестве ингибиторов 11-бета-гидроксистероиддегидрогеназы 1
JP5161869B2 (ja) * 2006-04-21 2013-03-13 イーライ リリー アンド カンパニー 11−β−ヒドロキシステロイドデヒドロゲナーゼ1の阻害剤としての、シクロヘキシルピラゾール−ラクタム誘導体
AU2007240450B2 (en) 2006-04-21 2011-12-22 Eli Lilly And Company Cyclohexylimidazole lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1
EA016415B1 (ru) 2006-04-24 2012-04-30 Эли Лилли Энд Компани Ингибиторы 11-бета-гидроксистероид-дегидрогеназы типа 1
CN101432263B (zh) 2006-04-24 2012-03-07 伊莱利利公司 作为11-β-羟类固醇脱氢酶1抑制剂的取代的吡咯烷酮类
DK2021337T3 (da) 2006-04-25 2010-03-29 Lilly Co Eli Inhibitorer af 11-beta-hydroxysteroid-dehydrogenase-1
JP5101602B2 (ja) 2006-04-25 2012-12-19 イーライ リリー アンド カンパニー 11−β−ヒドロキシステロイドデヒドロゲナーゼ1の阻害剤
CN101432265B (zh) 2006-04-25 2011-12-14 伊莱利利公司 11-β-羟类固醇脱氢酶1的抑制剂
DK2049513T3 (da) * 2006-04-28 2012-02-27 Lilly Co Eli Piperidinylsubstituerede pyrrolidinoner som inhibitorer af 11-beta-hydroxysteroiddehydrogenase 1
EP2025674A1 (fr) 2007-08-15 2009-02-18 sanofi-aventis Tetrahydronaphthaline substituée, son procédé de fabrication et son utilisation en tant que médicament
EP2243479A3 (fr) 2009-04-20 2011-01-19 Abbott Laboratories Nouvel amide et dérivés d'amidine et utilisations associées
WO2011068927A2 (fr) * 2009-12-04 2011-06-09 Abbott Laboratories Inhibiteurs de la 11-β-hydroxystéroïde déshydrogénase de type 1 (11b-hsd1) et leurs utilisations
WO2011107494A1 (fr) 2010-03-03 2011-09-09 Sanofi Nouveaux dérivés aromatiques de glycoside, médicaments contenants ces composés, et leur utilisation
EP2582709B1 (fr) 2010-06-18 2018-01-24 Sanofi Dérivés d'azolopyridin-3-one en tant qu'inhibiteurs de lipases et de phospholipases
US8530413B2 (en) 2010-06-21 2013-09-10 Sanofi Heterocyclically substituted methoxyphenyl derivatives with an oxo group, processes for preparation thereof and use thereof as medicaments
TW201215387A (en) 2010-07-05 2012-04-16 Sanofi Aventis Spirocyclically substituted 1,3-propane dioxide derivatives, processes for preparation thereof and use thereof as a medicament
TW201221505A (en) 2010-07-05 2012-06-01 Sanofi Sa Aryloxyalkylene-substituted hydroxyphenylhexynoic acids, process for preparation thereof and use thereof as a medicament
TW201215388A (en) 2010-07-05 2012-04-16 Sanofi Sa (2-aryloxyacetylamino)phenylpropionic acid derivatives, processes for preparation thereof and use thereof as medicaments
WO2012120056A1 (fr) 2011-03-08 2012-09-13 Sanofi Dérivés oxathiazine tétra-substitués, procédé pour leur préparation, utilisation en tant que médicament, agent pharmaceutique contenant ces dérivés et utilisation
EP2683704B1 (fr) 2011-03-08 2014-12-17 Sanofi Dérivés oxathiazine ramifiés, procédé pour leur préparation, utilisation en tant que médicament, agents pharmaceutiques contenant ces dérivés et leur utilisation
EP2766349B1 (fr) 2011-03-08 2016-06-01 Sanofi Dérivés d'oxathiazine substitués par des carbocycles ou des hétérocycles, leur procédé de préparation, médicaments contenant ces composés et leur utilisation
US8828994B2 (en) 2011-03-08 2014-09-09 Sanofi Di- and tri-substituted oxathiazine derivatives, method for the production thereof, use thereof as medicine and drug containing said derivatives and use thereof
EP2683699B1 (fr) 2011-03-08 2015-06-24 Sanofi Dérivés oxathiazine di- et tri-substitués, procédé pour leur préparation, utilisation en tant que médicament, agent pharmaceutique contenant ces dérivés et utilisation
WO2013037390A1 (fr) 2011-09-12 2013-03-21 Sanofi Dérivés amides d'acide 6-(4-hydroxyphényl)-3-styryl-1h-pyrazolo[3,4-b]pyridine-4-carboxylique en tant qu'inhibiteurs de kinase
WO2013045413A1 (fr) 2011-09-27 2013-04-04 Sanofi Dérivés d'amide d'acide 6-(4-hydroxyphényl)-3-alkyl-1h-pyrazolo[3,4-b] pyridine-4-carboxylique utilisés comme inhibiteurs de kinase
EP3235813A1 (fr) 2016-04-19 2017-10-25 Cidqo 2012, S.L. Dérivés aza-tétra-cycliques
TWI822716B (zh) * 2017-12-21 2023-11-21 大陸商廣東眾生睿創生物科技有限公司 作為ppar促效劑的吡咯啶衍生物的非晶形及其製備方法
CN110483514B (zh) 2019-09-16 2022-06-14 启元生物(杭州)有限公司 一种氰基取代的环肼衍生物及其应用
CN110724142B (zh) * 2019-10-29 2022-09-02 启元生物(杭州)有限公司 一种作为jak激酶抑制剂的酰胺或磺酰胺取代的肼衍生物

Family Cites Families (23)

* Cited by examiner, † Cited by third party
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WO2004056744A1 (fr) * 2002-12-23 2004-07-08 Janssen Pharmaceutica N.V. Adamantyl acetamides utilises comme inhibiteurs de la hydroxysteroide deshydrogenase
AU2005240784C1 (en) 2004-05-07 2011-12-22 Janssen Pharmaceutica N.V. Pyrrolidin-2-one and piperidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors
AU2005240785B2 (en) * 2004-05-07 2011-02-03 Janssen Pharmaceutica N.V. Adamantyl pyrrolidin-2-one derivatives as 11-beta hydroxysteroid dehydrogenase inhibitors
EP1802623A1 (fr) 2004-10-12 2007-07-04 Novo Nordisk A/S Composes spiro actifs du type a- hydroxysteroide deshydrogenase de type 1
US7713979B2 (en) * 2004-10-29 2010-05-11 Eli Lilly And Company Cycloalkyl lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1
ES2547724T3 (es) 2004-11-10 2015-10-08 Incyte Corporation Compuestos de lactama y su uso como productos farmacéuticos
WO2006068992A1 (fr) 2004-12-20 2006-06-29 Eli Lilly And Company Derives de cycloalkyl-lactame utilises en tant qu'inhibiteurs de la 11-beta-hydroxysteroide deshydrogenase 1
DE602005008282D1 (de) 2004-12-21 2008-08-28 Lilly Co Eli Cycloalkyl-lactam-derivate als inhibitoren von 11-beta-hydroxysteroiddehydrogenase 1
JPWO2006104280A1 (ja) * 2005-03-31 2008-09-11 武田薬品工業株式会社 糖尿病の予防・治療剤
WO2007066921A1 (fr) * 2005-12-08 2007-06-14 Ho Young Lee Structure obtenue par collage d'une matiere etrangere et d'une plaque de compression digitale pour pieds chauds
WO2007084314A2 (fr) 2006-01-12 2007-07-26 Incyte Corporation MODULATEURS de la 11-ß HYDROXYSTEROIDE DESHYDROGENASE DE TYPE 1, LEURS COMPOSITIONS PHARMACEUTIQUES ET LEURS PROCEDES D'UTILISATION
JP5161869B2 (ja) 2006-04-21 2013-03-13 イーライ リリー アンド カンパニー 11−β−ヒドロキシステロイドデヒドロゲナーゼ1の阻害剤としての、シクロヘキシルピラゾール−ラクタム誘導体
AU2007240450B2 (en) 2006-04-21 2011-12-22 Eli Lilly And Company Cyclohexylimidazole lactam derivatives as inhibitors of 11-beta-hydroxysteroid dehydrogenase 1
EA014718B1 (ru) * 2006-04-21 2011-02-28 Эли Лилли Энд Компани Производные бифениламидлактама в качестве ингибиторов 11-бета-гидроксистероиддегидрогеназы 1
CN101432263B (zh) * 2006-04-24 2012-03-07 伊莱利利公司 作为11-β-羟类固醇脱氢酶1抑制剂的取代的吡咯烷酮类
EA016415B1 (ru) 2006-04-24 2012-04-30 Эли Лилли Энд Компани Ингибиторы 11-бета-гидроксистероид-дегидрогеназы типа 1
DK2021337T3 (da) * 2006-04-25 2010-03-29 Lilly Co Eli Inhibitorer af 11-beta-hydroxysteroid-dehydrogenase-1
CN101432265B (zh) 2006-04-25 2011-12-14 伊莱利利公司 11-β-羟类固醇脱氢酶1的抑制剂
JP5101602B2 (ja) * 2006-04-25 2012-12-19 イーライ リリー アンド カンパニー 11−β−ヒドロキシステロイドデヒドロゲナーゼ1の阻害剤
DK2049513T3 (da) 2006-04-28 2012-02-27 Lilly Co Eli Piperidinylsubstituerede pyrrolidinoner som inhibitorer af 11-beta-hydroxysteroiddehydrogenase 1
US20090008890A1 (en) * 2007-06-13 2009-01-08 Woodford James R Suspension system for an all-terrain vehicle
CL2008001839A1 (es) 2007-06-21 2009-01-16 Incyte Holdings Corp Compuestos derivados de 2,7-diazaespirociclos, inhibidores de 11-beta hidroxil esteroide deshidrogenasa tipo 1; composicion farmaceutica que comprende a dichos compuestos; utiles para tratar la obesidad, diabetes, intolerancia a la glucosa, diabetes tipo ii, entre otras enfermedades.
WO2011068927A2 (fr) * 2009-12-04 2011-06-09 Abbott Laboratories Inhibiteurs de la 11-β-hydroxystéroïde déshydrogénase de type 1 (11b-hsd1) et leurs utilisations

Also Published As

Publication number Publication date
AU2007244955B2 (en) 2011-12-08
IL194810A0 (en) 2009-09-22
ECSP088833A (es) 2008-11-27
KR101059614B1 (ko) 2011-08-25
PT2021336E (pt) 2010-07-19
EA200870470A1 (ru) 2009-04-28
CO6140034A2 (es) 2010-03-19
MX2008013649A (es) 2008-11-04
BRPI0710467A2 (pt) 2011-08-16
US8153807B2 (en) 2012-04-10
NZ571176A (en) 2011-10-28
CY1110753T1 (el) 2015-06-10
WO2007127688A2 (fr) 2007-11-08
RS51450B (sr) 2011-04-30
TNSN08417A1 (en) 2010-04-14
ES2345792T3 (es) 2010-10-01
HK1126208A1 (en) 2009-08-28
SI2021336T1 (sl) 2010-11-30
UA94741C2 (en) 2011-06-10
US20090111809A1 (en) 2009-04-30
WO2007127688A3 (fr) 2007-12-21
CR10401A (es) 2009-01-14
DE602007007473D1 (en) 2010-08-12
ATE472542T1 (de) 2010-07-15
MY148079A (en) 2013-02-28
EP2021336A2 (fr) 2009-02-11
CN101432275A (zh) 2009-05-13
CN101432275B (zh) 2013-10-30
CA2646624C (fr) 2013-08-06
NO20084318L (no) 2008-10-15
AU2007244955A1 (en) 2007-11-08
JP5269765B2 (ja) 2013-08-21
KR20090034797A (ko) 2009-04-08
DK2021336T3 (da) 2010-09-13
ZA200808687B (en) 2010-01-27
EA015106B1 (ru) 2011-06-30
CR10402A (es) 2009-07-13
EP2021336B1 (fr) 2010-06-30
CA2646624A1 (fr) 2007-11-08
JP2009534468A (ja) 2009-09-24
HRP20100397T1 (hr) 2010-09-30
IL194810A (en) 2012-12-31
PL2021336T3 (pl) 2010-11-30

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