Literature DB >> 24900474

Discovery of BMS-846372, a Potent and Orally Active Human CGRP Receptor Antagonist for the Treatment of Migraine.

Guanglin Luo1, Ling Chen1, Charles M Conway1, Rex Denton1, Deborah Keavy1, Michael Gulianello1, Yanling Huang1, Walter Kostich1, Kimberley A Lentz1, Stephen E Mercer1, Richard Schartman1, Laura Signor1, Marc Browning1, John E Macor1, Gene M Dubowchik1.   

Abstract

Calcitonin gene-related peptide (CGRP) receptor antagonists have been clinically shown to be effective in the treatment of migraine, but identification of potent and orally bioavailable compounds has been challenging. Herein, we describe the conceptualization, synthesis, and preclinical characterization of a potent, orally active CGRP receptor antagonist 5 (BMS-846372). Compound 5 has good oral bioavailability in rat, dog, and cynomolgus monkeys and overall attractive preclinical properties including strong (>50% inhibition) exposure-dependent in vivo efficacy in a marmoset migraine model.

Entities:  

Keywords:  CGRP; CGRP receptor; antagonist; migraine

Year:  2012        PMID： 24900474      PMCID： PMC4025799          DOI： 10.1021/ml300021s

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


  24 in total

1.  Tandem catalysis: the sequential mediation of olefin metathesis, hydrogenation, and hydrogen transfer with single-component Ru complexes.

Authors:  J Louie; C W Bielawski; R H Grubbs
Journal:  J Am Chem Soc       Date:  2001-11-14       Impact factor: 15.419

Review 2.  Excellent tolerability but relatively low initial clinical efficacy of telcagepant in migraine.

Authors:  Peer Tfelt-Hansen
Journal:  Headache       Date:  2010-11-10       Impact factor: 5.887

Review 3.  Calcitonin gene-related peptide antagonists as treatments of migraine and other primary headaches.

Authors:  Peter J Goadsby
Journal:  Drugs       Date:  2005       Impact factor: 9.546

4.  Conjugate addition of 2- and 4-pyridylcuprates: an expeditious asymmetric synthesis of natural (-)-evoninic acid.

Authors:  Alan C Spivey; Lena Shukla; Judy F Hayler
Journal:  Org Lett       Date:  2007-02-09       Impact factor: 6.005

5.  Prevalence and burden of migraine in the United States: data from the American Migraine Study II.

Authors:  R B Lipton; W F Stewart; S Diamond; M L Diamond; M Reed
Journal:  Headache       Date:  2001 Jul-Aug       Impact factor: 5.887

6.  Randomized controlled study of telcagepant plus ibuprofen or acetaminophen in migraine.

Authors:  David J Hewitt; Vincent Martin; Richard B Lipton; Jan Brandes; Paulette Ceesay; Regina Gottwald; Eleanor Schaefer; Christopher Lines; Tony W Ho
Journal:  Headache       Date:  2011-04       Impact factor: 5.887

7.  Potent, orally bioavailable calcitonin gene-related peptide receptor antagonists for the treatment of migraine: discovery of N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1- (2,2,2-trifluoroethyl)azepan-3-yl]-4- (2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin- 1-yl)piperidine-1-carboxamide (MK-0974).

Authors:  Daniel V Paone; Anthony W Shaw; Diem N Nguyen; Christopher S Burgey; James Z Deng; Stefanie A Kane; Kenneth S Koblan; Christopher A Salvatore; Scott D Mosser; Victor K Johnston; Bradley K Wong; Cynthia M Miller-Stein; James C Hershey; Samuel L Graham; Joseph P Vacca; Theresa M Williams
Journal:  J Med Chem       Date:  2007-10-11       Impact factor: 7.446

8.  Efforts to expand the genetic alphabet: identification of a replicable unnatural DNA self-pair.

Authors:  Allison A Henry; Anne Goldbech Olsen; Shigeo Matsuda; Chengzhi Yu; Bernhard H Geierstanger; Floyd E Romesberg
Journal:  J Am Chem Soc       Date:  2004-06-09       Impact factor: 15.419

9.  Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine.

Authors:  Jes Olesen; Hans-Christoph Diener; Ingo W Husstedt; Peter J Goadsby; David Hall; Ulrich Meier; Stephane Pollentier; Lynna M Lesko
Journal:  N Engl J Med       Date:  2004-03-11       Impact factor: 91.245

Review 10.  Neurobiology of migraine.

Authors:  P J Goadsby; A R Charbit; A P Andreou; S Akerman; P R Holland
Journal:  Neuroscience       Date:  2009-03-19       Impact factor: 3.590
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  5 in total

1.  Transition-metal-free C-H amidation and chlorination: synthesis of N/N'-mono-substituted imidazopyridin-2-ones from N-pyridyl-N-hydroxylamine intermediates.

Authors:  Katarzyna N Lee; Dominique N Spiegowski; Johnny W Lee; Sanghyun Lim; Fuhua Zhao; Ming-Yu Ngai
Journal:  Chem Commun (Camb)       Date:  2018-06-19       Impact factor: 6.222

Review 2.  CGRP mechanism antagonists and migraine management.

Authors:  Nazia Karsan; Peter J Goadsby
Journal:  Curr Neurol Neurosci Rep       Date:  2015-05       Impact factor: 5.081

3.  Partially Saturated Bicyclic Heteroaromatics as an sp(3) -Enriched Fragment Collection.

Authors:  David G Twigg; Noriyasu Kondo; Sophie L Mitchell; Warren R J D Galloway; Hannah F Sore; Andrew Madin; David R Spring
Journal:  Angew Chem Int Ed Engl       Date:  2016-09-06       Impact factor: 15.336

Review 4.  G protein-coupled receptors: structure- and function-based drug discovery.

Authors:  Dehua Yang; Qingtong Zhou; Viktorija Labroska; Shanshan Qin; Sanaz Darbalaei; Yiran Wu; Elita Yuliantie; Linshan Xie; Houchao Tao; Jianjun Cheng; Qing Liu; Suwen Zhao; Wenqing Shui; Yi Jiang; Ming-Wei Wang
Journal:  Signal Transduct Target Ther       Date:  2021-01-08

5.  Ubrogepant Is Not Associated With Clinically Meaningful Elevations of Alanine Aminotransferase in Healthy Adult Males.

Authors:  Wendy Ankrom; Phung Bondiskey; Chi-Chung Li; John Palcza; Wen Liu; Marissa F Dockendorf; Catherine Matthews; Deborah Panebianco; Tom Reynders; John A Wagner; Abhijeet Jakate; Sofie Mesens; Walter K Kraft; Eugene E Marcantonio
Journal:  Clin Transl Sci       Date:  2020-01-03       Impact factor: 4.689
  5 in total

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