Literature DB >> 24944750

Discovery of MK-4409, a Novel Oxazole FAAH Inhibitor for the Treatment of Inflammatory and Neuropathic Pain.

Harry R Chobanian1, Yan Guo1, Ping Liu1, Marc D Chioda1, Selena Fung1, Thomas J Lanza1, Linda Chang1, Raman K Bakshi1, James P Dellureficio1, Qingmei Hong1, Mark McLaughlin1, Kevin M Belyk1, Shane W Krska1, Amanda K Makarewicz1, Elliot J Martel1, Joseph F Leone1, Lisa Frey1, Bindhu Karanam1, Maria Madeira1, Raul Alvaro1, Joyce Shuman1, Gino Salituro1, Jenna L Terebetski1, Nina Jochnowitz1, Shruti Mistry1, Erin McGowan1, Richard Hajdu1, Mark Rosenbach1, Catherine Abbadie1, Jessica P Alexander1, Lin-Lin Shiao1, Kathleen M Sullivan1, Ravi P Nargund1, Matthew J Wyvratt1, Linus S Lin1, Robert J DeVita1.   

Abstract

We report herein the identification of MK-4409, a potent and selective fatty acid amide hydrolase (FAAH) inhibitor. Starting from a high throughput screening (HTS) hit, medicinal chemistry efforts focused on optimizing of FAAH inhibition in vitro potency, improving the pharmacokinetic (PK) profile, and increasing in vivo efficacy in rodent inflammatory and neuropathic pain assays.

Entities:  

Keywords:  CNS; FAAH; Fatty acid amide hydrolase; MK-4409; enzyme; inflammatory pain; inhibitor; neuropathic pain; oxazole; pyrazole

Year:  2014        PMID： 24944750      PMCID： PMC4060928          DOI： 10.1021/ml5001239

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


  19 in total

1.  Reversible inhibitors of fatty acid amide hydrolase that promote analgesia: evidence for an unprecedented combination of potency and selectivity.

Authors:  Aron H Lichtman; Donmienne Leung; Christopher C Shelton; Alan Saghatelian; Christophe Hardouin; Dale L Boger; Benjamin F Cravatt
Journal:  J Pharmacol Exp Ther       Date:  2004-06-30       Impact factor: 4.030

2.  Suzuki coupling of oxazoles.

Authors:  Emmanuel Ferrer Flegeau; Matthew E Popkin; Michael F Greaney
Journal:  Org Lett       Date:  2006-06-08       Impact factor: 6.005

3.  Supersensitivity to anandamide and enhanced endogenous cannabinoid signaling in mice lacking fatty acid amide hydrolase.

Authors:  B F Cravatt; K Demarest; M P Patricelli; M H Bracey; D K Giang; B R Martin; A H Lichtman
Journal:  Proc Natl Acad Sci U S A       Date:  2001-07-24       Impact factor: 11.205

4.  Discovery of PF-04457845: A Highly Potent, Orally Bioavailable, and Selective Urea FAAH Inhibitor.

Authors:  Douglas S Johnson; Cory Stiff; Scott E Lazerwith; Suzanne R Kesten; Lorraine K Fay; Mark Morris; David Beidler; Marya B Liimatta; Sarah E Smith; David T Dudley; Nalini Sadagopan; Shobha N Bhattachar; Stephen J Kesten; Tyzoon K Nomanbhoy; Benjamin F Cravatt; Kay Ahn
Journal:  ACS Med Chem Lett       Date:  2011-02-10       Impact factor: 4.345

5.  Antidepressant-like activity and modulation of brain monoaminergic transmission by blockade of anandamide hydrolysis.

Authors:  G Gobbi; F R Bambico; R Mangieri; M Bortolato; P Campolongo; M Solinas; T Cassano; M G Morgese; G Debonnel; A Duranti; A Tontini; G Tarzia; M Mor; V Trezza; S R Goldberg; V Cuomo; D Piomelli
Journal:  Proc Natl Acad Sci U S A       Date:  2005-12-13       Impact factor: 11.205

6.  Identification of potent, noncovalent fatty acid amide hydrolase (FAAH) inhibitors.

Authors:  Darin J Gustin; Zhihua Ma; Xiaoshan Min; Yihong Li; Christine Hedberg; Cris Guimaraes; Amy C Porter; Michelle Lindstrom; Dianna Lester-Zeiner; Guifen Xu; Timothy J Carlson; Shouhua Xiao; Cesar Meleza; Richard Connors; Zhulun Wang; Frank Kayser
Journal:  Bioorg Med Chem Lett       Date:  2011-02-17       Impact factor: 2.823

7.  Cyclohexylcarbamic acid 3'- or 4'-substituted biphenyl-3-yl esters as fatty acid amide hydrolase inhibitors: synthesis, quantitative structure-activity relationships, and molecular modeling studies.

Authors:  Marco Mor; Silvia Rivara; Alessio Lodola; Pier Vincenzo Plazzi; Giorgio Tarzia; Andrea Duranti; Andrea Tontini; Giovanni Piersanti; Satish Kathuria; Daniele Piomelli
Journal:  J Med Chem       Date:  2004-10-07       Impact factor: 7.446

Review 8.  Evidence that adjuvant arthritis in the rat is associated with chronic pain.

Authors:  F C Colpaert
Journal:  Pain       Date:  1987-02       Impact factor: 6.961

9.  Analogs of MK-499 are differentially affected by a mutation in the S6 domain of the hERG K+ channel.

Authors:  Jerzy Karczewski; Jixin Wang; Stefanie A Kane; Laszlo Kiss; Kenneth S Koblan; J Christopher Culberson; Robert H Spencer
Journal:  Biochem Pharmacol       Date:  2009-02-27       Impact factor: 5.858

10.  Mice lacking fatty acid amide hydrolase exhibit a cannabinoid receptor-mediated phenotypic hypoalgesia.

Authors:  Aron H Lichtman; Christopher C Shelton; Tushar Advani; Benjamin F Cravatt
Journal:  Pain       Date:  2004-06       Impact factor: 6.961
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  3 in total

1.  Safety, Tolerability, and Pharmacokinetics of FAAH Inhibitor BIA 10-2474: A Double-Blind, Randomized, Placebo-Controlled Study in Healthy Volunteers.

Authors:  José-Francisco Rocha; Ana Santos; Helena Gama; Paul Moser; Amílcar Falcão; Peter Pressman; A Wallace Hayes; Patricio Soares-da-Silva
Journal:  Clin Pharmacol Ther       Date:  2021-06-24       Impact factor: 6.903

2.  Discovery of a Potent, Long-Acting, and CNS-Active Inhibitor (BIA 10-2474) of Fatty Acid Amide Hydrolase.

Authors:  László E Kiss; Alexandre Beliaev; Humberto S Ferreira; Carla P Rosa; Maria João Bonifácio; Ana I Loureiro; Nuno M Pires; P Nuno Palma; Patrício Soares-da-Silva
Journal:  ChemMedChem       Date:  2018-09-11       Impact factor: 3.466

3.  Pharmacological characterization of a novel, potent, selective, and orally active fatty acid amide hydrolase inhibitor, PKM-833 [(R)-N-(pyridazin-3-yl)-4-(7-(trifluoromethyl)chroman-4-yl)piperazine-1-carboxamide] in rats: Potential for the treatment of inflammatory pain.

Authors:  Toshiya Endo; Takashi Takeuchi; Shunsuke Maehara
Journal:  Pharmacol Res Perspect       Date:  2020-04
  3 in total

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