Discovery of 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxamides as potent and selective CB2 receptor agonists.

Autor: Han S; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA. Electronic address: shan@arenapharm.com., Thoresen L; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Zhu X; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Narayanan S; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Jung JK; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Strah-Pleynet S; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Decaire M; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Choi K; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Xiong Y; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Yue D; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Semple G; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Thatte J; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Solomon M; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Fu L; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Whelan K; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Al-Shamma H; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Gatlin J; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Chen R; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Dang H; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Pride C; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Gaidarov I; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Unett DJ; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Behan DP; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Sadeque A; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Usmani KA; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Chen C; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Edwards J; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Morgan M; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA., Jones RM; Arena Pharmaceuticals, 6154 Nancy Ridge Drive, San Diego, CA 92121, USA.
Jazyk: angličtina
Zdroj: Bioorganic & medicinal chemistry letters [Bioorg Med Chem Lett] 2015 Jan 15; Vol. 25 (2), pp. 322-6. Date of Electronic Publication: 2014 Nov 26.
DOI: 10.1016/j.bmcl.2014.11.040
Abstrakt: The design and synthesis of novel 1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalen-4-carboxamide CB2 selective ligands for the potential treatment of pain is described. Compound (R,R)-25 has good balance between CB2 agonist potency and selectivity over CB1, and possesses overall favorable pharmaceutical properties. It also demonstrated robust in vivo efficacy mediated via CB2 activation in the rodent models of inflammatory and osteoarthritis pain after oral administration.
(Copyright © 2014 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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