Literature DB >> 24900461

Discovery of MK-7725, A Potent, Selective Bombesin Receptor Subtype-3 Agonist for the Treatment of Obesity.

Harry R Chobanian1, Yan Guo1, Ping Liu1, Marc Chioda1, Thomas J Lanza1, Linda Chang1, Theresa M Kelly1, Yanqing Kan1, Oksana Palyha1, Xiao-Ming Guan1, Donald J Marsh1, Joseph M Metzger1, Judith N Gorski1, Kate Raustad1, Sheng-Ping Wang1, Alison M Strack1, Randy Miller1, Jianmei Pang1, Maria Madeira1, Kathy Lyons1, Jasminka Dragovic1, Marc L Reitman1, Ravi P Nargund1, Linus S Lin1.   

Abstract

Extensive structure-activity relationship studies of a series derived from atropisomer 1, a previously described chiral benzodiazepine sulfonamide series, led to a potent, brain penetrant and selective compound with excellent preclinical pharmacokinetic across species. We also describe the utilization of a high throughput mouse pharmacodynamic assay which allowed for expedient assessment of pharmacokinetic and brain distribution.

Entities:  

Keywords:  BRS-3; Bombesin receptor subtype-3; MK-7725; agonist; atropisomer; benzodiazepine sulfonamide; obesity

Year:  2012        PMID： 24900461      PMCID： PMC4025675          DOI： 10.1021/ml200304j

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


  15 in total

Review 1.  Nonpeptidic ligands for peptide-activated G protein-coupled receptors.

Authors:  Jade S Blakeney; Robert C Reid; Giang T Le; David P Fairlie
Journal:  Chem Rev       Date:  2007-07       Impact factor: 60.622

2.  Factors influencing the interconversion of a new class of dibenzodiazepine sulfonamide atropisomers.

Authors:  Christopher J Welch; Xiaoyi Gong; Wes Schafer; Harry Chobanian; Linus Lin; Mirlinda Biba; Ping Liu; Yan Guo; Adam Beard
Journal:  Chirality       Date:  2009       Impact factor: 2.437

3.  Synthesis and SAR of derivatives based on 2-biarylethylimidazole as bombesin receptor subtype-3 (BRS-3) agonists for the treatment of obesity.

Authors:  Jian Liu; Shuwen He; Tianying Jian; Peter H Dobbelaar; Iyassu K Sebhat; Linus S Lin; Allan Goodman; Cheng Guo; Peter R Guzzo; Mark Hadden; Alan J Henderson; Kevin Pattamana; Megan Ruenz; Bruce J Sargent; Brian Swenson; Larry Yet; Constantin Tamvakopoulos; Qianping Peng; Jie Pan; Yanqing Kan; Oksana Palyha; Theresa M Kelly; Xiao-Ming Guan; Andrew D Howard; Donald J Marsh; Joseph M Metzger; Marc L Reitman; Matthew J Wyvratt; Ravi P Nargund
Journal:  Bioorg Med Chem Lett       Date:  2010-02-21       Impact factor: 2.823

4.  Catalysts for Suzuki-Miyaura coupling processes: scope and studies of the effect of ligand structure.

Authors:  Timothy E Barder; Shawn D Walker; Joseph R Martinelli; Stephen L Buchwald
Journal:  J Am Chem Soc       Date:  2005-04-06       Impact factor: 15.419

5.  Pyridinesulfonylureas and pyridinesulfonamides as selective bombesin receptor subtype-3 (BRS-3) agonists.

Authors:  Michael M-C Lo; Harry R Chobanian; Oksana Palyha; Yanqing Kan; Theresa M Kelly; Xiao-Ming Guan; Marc L Reitman; Jasminka Dragovic; Kathryn A Lyons; Ravi P Nargund; Linus S Lin
Journal:  Bioorg Med Chem Lett       Date:  2011-02-25       Impact factor: 2.823

6.  Discovery of benzodiazepine sulfonamide-based bombesin receptor subtype 3 agonists and their unusual chirality.

Authors:  Ping Liu; Thomas J Lanza; Marc Chioda; Carrie Jones; Harry R Chobanian; Yan Guo; Linda Chang; Theresa M Kelly; Yanqing Kan; Oksana Palyha; Xiao-Ming Guan; Donald J Marsh; Joseph M Metzger; Katie Ramsay; Sheng-Ping Wang; Alison M Strack; Randy Miller; Jianmei Pang; Kathy Lyons; Jasminka Dragovic; Jian G Ning; Wes A Schafer; Christopher J Welch; Xiaoyi Gong; Ying-Duo Gao; Viktor Hornak; Richard G Ball; Nancy Tsou; Marc L Reitman; Matthew J Wyvratt; Ravi P Nargund; Linus S Lin
Journal:  ACS Med Chem Lett       Date:  2011-10-03       Impact factor: 4.345

7.  Discovery of substituted biphenyl imidazoles as potent, bioavailable bombesin receptor subtype-3 agonists.

Authors:  Shuwen He; Peter H Dobbelaar; Jian Liu; Tianying Jian; Iyassu K Sebhat; Linus S Lin; Allan Goodman; Cheng Guo; Peter R Guzzo; Mark Hadden; Alan J Henderson; Megan Ruenz; Bruce J Sargent; Larry Yet; Theresa M Kelly; Oksana Palyha; Yanqing Kan; Jie Pan; Howard Chen; Donald J Marsh; Lauren P Shearman; Alison M Strack; Joseph M Metzger; Scott D Feighner; Carina Tan; Andrew D Howard; Constantin Tamvakopoulos; Qianping Peng; Xiao-Ming Guan; Marc L Reitman; Arthur A Patchett; Matthew J Wyvratt; Ravi P Nargund
Journal:  Bioorg Med Chem Lett       Date:  2010-02-04       Impact factor: 2.823

8.  Discovery of small molecule agonists for the bombesin receptor subtype 3 (BRS-3) based on an omeprazole lead.

Authors:  David L Carlton; Lissa J Collin-Smith; Alejandro J Daniels; David N Deaton; Aaron S Goetz; Christopher P Laudeman; Thomas R Littleton; David L Musso; Ronda J Ott Morgan; Jerzy R Szewczyk; Cunyu Zhang
Journal:  Bioorg Med Chem Lett       Date:  2008-09-11       Impact factor: 2.823

9.  Mice lacking bombesin receptor subtype-3 develop metabolic defects and obesity.

Authors:  H Ohki-Hamazaki; K Watase; K Yamamoto; H Ogura; M Yamano; K Yamada; H Maeno; J Imaki; S Kikuyama; E Wada; K Wada
Journal:  Nature       Date:  1997-11-13       Impact factor: 49.962

10.  Factors contributing to obesity in bombesin receptor subtype-3-deficient mice.

Authors:  Ellen E Ladenheim; Nahketah L Hamilton; Robert R Behles; Sheng Bi; Lori L Hampton; James F Battey; Timothy H Moran
Journal:  Endocrinology       Date:  2007-11-26       Impact factor: 4.736
View more
  2 in total

Review 1.  Bombesin receptor subtype 3 as a potential target for obesity and diabetes.

Authors:  Nieves González; Paola Moreno; Robert T Jensen
Journal:  Expert Opin Ther Targets       Date:  2015-06-12       Impact factor: 6.902

2.  Bombesin receptor subtype-3-expressing neurons regulate energy homeostasis through a novel neuronal pathway in the hypothalamus.

Authors:  Minoru Maruyama; Natsu Hotta; Yasunori Nio; Kenichi Hamagami; Toshimi Nagi; Masaaki Funata; Junichi Sakamoto; Masanori Nakakariya; Nobuyuki Amano; Mayumi Nishida; Tomohiro Okawa; Yasuyoshi Arikawa; Shinobu Sasaki; Shizuo Kasai; Yasutaka Nagisa; Yugo Habata; Masaaki Mori
Journal:  Brain Behav       Date:  2017-12-15       Impact factor: 2.708
  2 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.