Literature DB >> 24900382

Discovery of 2-Alkyl-1-arylsulfonylprolinamides as 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors.

Jianxin Yu1, Haiyan Liu1, Guangxin Xia2, Lin Liu2, Zhenmin Xu1, Qian Chen1, Chen Ma1, Xing Sun1, Jiajun Xu1, Hua Li1, Ping Li1, Yufang Shi1, Bing Xiong3, Xuejun Liu1, Jingkang Shen2.   

Abstract

On the basis of scaffold hopping, a novel series of 2-alkyl-1-arylsulfonylprolinamides was discovered as 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) inhibitors. A representative compound 4ek, obtained through SAR and structure optimization studies, demonstrates excellent in vitro potency against 11β-HSD-1 and dose-dependent in vivo inhibition of 11β-HSD-1 in a prednisone/prednisolone transformation biomarker study in mice.

Entities:  

Keywords:  11β-hydroxysteroid dehydrogenase type 1; 2-alkylproline; enzyme inhibitor; metabolic syndrome; prolinamide; sulfonamide

Year:  2012        PMID： 24900382      PMCID： PMC4025654          DOI： 10.1021/ml300144n

Source DB:  PubMed          Journal:  ACS Med Chem Lett        ISSN： 1948-5875            Impact factor:   4.345


  19 in total

1.  Effects of an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, MK-0916, in patients with type 2 diabetes mellitus and metabolic syndrome.

Authors:  P U Feig; S Shah; A Hermanowski-Vosatka; D Plotkin; M S Springer; S Donahue; C Thach; E J Klein; E Lai; K D Kaufman
Journal:  Diabetes Obes Metab       Date:  2011-06       Impact factor: 6.577

2.  The development and SAR of pyrrolidine carboxamide 11beta-HSD1 inhibitors.

Authors:  Hengmiao Cheng; Jacqui Hoffman; Phuong Le; Sajiv K Nair; Stephan Cripps; Jean Matthews; Christopher Smith; Michele Yang; Stan Kupchinsky; Klaus Dress; Martin Edwards; Bridget Cole; Evan Walters; Christine Loh; Jacques Ermolieff; Andrea Fanjul; Ganesh B Bhat; Jocelyn Herrera; Tom Pauly; Natilie Hosea; Genevieve Paderes; Paul Rejto
Journal:  Bioorg Med Chem Lett       Date:  2010-03-10       Impact factor: 2.823

3.  Development and application of a scintillation proximity assay (SPA) for identification of selective inhibitors of 11beta-hydroxysteroid dehydrogenase type 1.

Authors:  S Mundt; K Solly; R Thieringer; A Hermanowski-Vosatka
Journal:  Assay Drug Dev Technol       Date:  2005-08       Impact factor: 1.738

4.  Discovery of adamantane ethers as inhibitors of 11beta-HSD-1: Synthesis and biological evaluation.

Authors:  Jyoti R Patel; Qi Shuai; Jurgen Dinges; Marty Winn; Marina Pliushchev; Steven Fung; Katina Monzon; William Chiou; Jiahong Wang; Liping Pan; Seble Wagaw; Kenneth Engstrom; Francis A Kerdesky; Kenton Longenecker; Russell Judge; Wenying Qin; Hovis M Imade; Deanne Stolarik; David W A Beno; Michael Brune; Linda E Chovan; Hing L Sham; Peer Jacobson; J T Link
Journal:  Bioorg Med Chem Lett       Date:  2006-10-28       Impact factor: 2.823

5.  Synthesis and biological evaluation of cyclic sulfamide derivatives as 11β-hydroxysteroid dehydrogenase 1 inhibitors.

Authors:  Se Hoan Kim; Ju Han Bok; Jae Hong Lee; Il Hyang Kim; Sung Wook Kwon; Gui Bin Lee; Seung Kyu Kang; Ji Seon Park; Won Hoon Jung; Hee Yeon Kim; Sang Dal Rhee; Sung Hoon Ahn; Myung Ae Bae; Deok Chan Ha; Ki Young Kim; Jin Hee Ahn
Journal:  ACS Med Chem Lett       Date:  2012-01-17       Impact factor: 4.345

Review 6.  Inhibitors of 11β-hydroxysteroid dehydrogenase type 1 in antidiabetic therapy.

Authors:  Minghan Wang
Journal:  Handb Exp Pharmacol       Date:  2011

7.  Transgenic amplification of glucocorticoid action in adipose tissue causes high blood pressure in mice.

Authors:  Hiroaki Masuzaki; Hiroshi Yamamoto; Christopher J Kenyon; Joel K Elmquist; Nicholas M Morton; Janice M Paterson; Hiroshi Shinyama; Matthew G F Sharp; Stewart Fleming; John J Mullins; Jonathan R Seckl; Jeffrey S Flier
Journal:  J Clin Invest       Date:  2003-07       Impact factor: 14.808

8.  The 11-beta-hydroxysteroid dehydrogenase type 1 inhibitor INCB13739 improves hyperglycemia in patients with type 2 diabetes inadequately controlled by metformin monotherapy.

Authors:  Julio Rosenstock; Salomon Banarer; Vivian A Fonseca; Silvio E Inzucchi; William Sun; Wenqing Yao; Gregory Hollis; Robert Flores; Richard Levy; William V Williams; Jonathan R Seckl; Reid Huber
Journal:  Diabetes Care       Date:  2010-04-22       Impact factor: 17.152

9.  Demonstration of proof of mechanism and pharmacokinetics and pharmacodynamic relationship with 4'-cyano-biphenyl-4-sulfonic acid (6-amino-pyridin-2-yl)-amide (PF-915275), an inhibitor of 11 -hydroxysteroid dehydrogenase type 1, in cynomolgus monkeys.

Authors:  B Ganesh Bhat; Natilie Hosea; Andrea Fanjul; Jocelyn Herrera; Justin Chapman; Fred Thalacker; Paul M Stewart; Paul A Rejto
Journal:  J Pharmacol Exp Ther       Date:  2007-10-05       Impact factor: 4.030

10.  11beta-HSD1 inhibition ameliorates metabolic syndrome and prevents progression of atherosclerosis in mice.

Authors:  Anne Hermanowski-Vosatka; James M Balkovec; Kang Cheng; Howard Y Chen; Melba Hernandez; Gloria C Koo; Cheryl B Le Grand; Zhihua Li; Joseph M Metzger; Steven S Mundt; Heather Noonan; Christian N Nunes; Steven H Olson; Bill Pikounis; Ning Ren; Nancy Robertson; James M Schaeffer; Kashmira Shah; Martin S Springer; Alison M Strack; Matthias Strowski; Kenneth Wu; Tsueiju Wu; Jianying Xiao; Bei B Zhang; Samuel D Wright; Rolf Thieringer
Journal:  J Exp Med       Date:  2005-08-15       Impact factor: 14.307
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  1 in total

1.  Optimization of 1,2,4-Triazolopyridines as Inhibitors of Human 11β-Hydroxysteroid Dehydrogenase Type 1 (11β-HSD-1).

Authors:  Jun Li; Lawrence J Kennedy; Haixia Wang; James J Li; Steven J Walker; Zhenqiu Hong; Stephen P O'Connor; Akbar Nayeem; Daniel M Camac; Paul E Morin; Steven Sheriff; Mengmeng Wang; Timothy Harper; Rajasree Golla; Ramakrishna Seethala; Thomas Harrity; Randolph P Ponticiello; Nathan N Morgan; Joseph R Taylor; Rachel Zebo; David A Gordon; Jeffrey A Robl
Journal:  ACS Med Chem Lett       Date:  2014-05-22       Impact factor: 4.345
  1 in total

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