581812-66-0Relevant articles and documents
Novel transient receptor potential vanilloid 1 receptor antagonists for the treatment of pain; Structure-activity relationships for ureas with quinoline, isoquinoline, quinazoline, phthalazine, quinoxaliue, and cinnoline moieties
Gomtsyan, Arthur,Bayburt, Erol K.,Schmidt, Robert G.,Guo, Zhu Zheng,Perner, Richard J.,Didomenico, Stanley,Koenig, John R.,Turner, Sean,Jinkerson, Tammie,Drizin, Irene,Hannick, Steven M.,Macri, Bryan S.,McDonald, Heath A.,Honore, Prisca,Wismer, Carol T.,Marsh, Kennan C.,Wetter, Jill,Stewart, Kent D.,Oie, Tetsuro,Jarvis, Michael F.,Surowy, Carol S.,Faltynek, Connie R.,Lee, Chih-Hung
, p. 744 - 752 (2005)
Novel transient receptor potential vanilloid 1 (TRPV1) receptor antagonists with various bicyclic heteroaromatic pharmacophores were synthesized, and their in vitro activity in blocking capsaicin activation of TRPV1 was assessed. On the basis of the contribution of these pharmacophores to the in vitro potency, they were ranked in the order of 5-isoquinoline > 8-quinoline = 8-quinazoline > 8-isoquinoline ≥ cinnoline ≈ phthalazine ≈ quinoxaline ≈ 5-quinoline. The 5-isoquinoline-containing compound 14a (hTRPV1 IC50 = 4 nM) exhibited 46% oral bioavailability and in vivo activity in animal models of visceral and inflammatory pain. Pharmacokinetic and pharmacological properties of 14a are substantial improvements over the profile of the high-throughput screening hit 1 (hTRPV1 IC50 = 22 nM), which was not efficacious in animal pain models and was not orally bioavailable.
In vitro structure-activity relationship and in vivo characterization of 1-(aryl)-3-(4-(amino)benzyl)urea transient receptor potential vanilloid 1 antagonists
Perner, Richard J.,DiDomenico, Stanley,Koenig, John R.,Gomtsyan, Arthur,Bayburt, Erol K.,Schmidt, Robert G.,Drizin, Irene,Guo, Zhu Zheng,Turner, Sean C.,Jinkerson, Tammie,Brown, Brian S.,Keddy, Ryan G.,Lukin, Kurill,McDonald, Heath A.,Honore, Prisca,Mikusa, Joe,Marsh, Kennan C.,Wetter, Jill M.,St. George, Karen,Jarvis, Michael F.,Faltynek, Connie R.,Lee, Chih-Hung
, p. 3651 - 3660 (2008/02/12)
The synthesis and structure-activity relationship of 1-(aryl)-3-(4-(amino) benzyl)urea transient receptor potential vanilloid 1 (TRPV1) antagonists are described. A variety of cyclic amine substituents are well tolerated at the 4-position of the benzyl group on compounds containing either an isoquinoline or indazole heterocyclic core. These compounds are potent antagonists of capsaicin activation of the TRPV1 receptor in vitro. Analogues, such as compound 45, have been identified that have good in vivo activity in animal models of pain. Further optimization of 45 resulted in compound 58 with substantially improved microsome stability and oral bioavailability, as well as in vivo activity.
Chromanylurea compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor and uses thereof
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Page/Page column 13; 23; 33, (2008/06/13)
Compounds that are antagonists of the VR1 receptor, having formula (I) [image] or a pharmaceutically acceptable salt, prodrug, or salt of a prodrug thereof, wherein A1, A2, A3, A4, R7, R8, R9, X, Y, Z, L, n, and m, are as defined herein, and are useful in disorders prevented or ameliorated by inhibiting the VR1 receptor.
Fused azabicyclic compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
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Page/Page column 30, (2010/02/11)
Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence and bladder overactivity.
Fused compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
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Page 14, (2008/06/13)
Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence, or bladder overactivity.
