- SUBSTITUTED BICYCLIC CARBOXAMIDE AND UREA DERIVATIVES AS VANILLOID RECEPTOR LIGANDS
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The invention relates to substituted bicyclic carboxamide and urea derivatives, to processes for the preparation thereof, to pharmaceutical compositions containing these compounds and also to the use of these compounds for preparing pharmaceutical compositions.
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- Substituted Bicyclic Carboxamide and Urea Compounds as Vanilloid Receptor Ligands
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Substituted bicyclic carboxamide and urea compounds corresponding to formula (I) processes for the preparation thereof, pharmaceutical compositions containing these compounds, and a method of using these compounds for the treatment and/or inhibition of pain and other conditions mediated at least in part via the vanilloid receptor 1.
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Page/Page column 31
(2012/05/20)
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- Identification of (R)-1-(5-tert-butyl-2,3-dihydro-1H-inden-1-yl)-3-(1H- indazol-4-yl)urea (ABT-102) as a potent TRPV1 antagonist for pain management
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Vanilloid receptor TRPV1 is a cation channel that can be activated by a wide range of noxious stimuli, including capsaicin, acid, and heat. Blockade of TRPV1 activation by selective antagonists is under investigation by several pharmaceutical companies in an effort to identify novel agents for pain management. Here we report that replacement of substituted benzyl groups by an indan rigid moiety in a previously described N-indazole-N′-benzyl urea series led to a number of TRPV1 antagonists with significantly increased in vitro potency and enhanced drug-like properties. Extensive evaluation of pharmacological, pharmacokinetic, and toxicological properties of synthesized analogs resulted in identification of (R)-7 (ABT-102). Both the analgesic activity and drug-like properties of (R)-7 support its advancement into clinical pain trials.
- Gomtsyan, Arthur,Bayburt, Erol K.,Schmidt, Robert G.,Surowy, Carol S.,Honore, Prisca,Marsh, Kennan C.,Hannick, Steven M.,McDonald, Heath A.,Wetter, Jill M.,Sullivan, James P.,Jarvis, Michael F.,Faltynek, Connie R.,Lee, Chih-Hung
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p. 392 - 395
(2008/09/17)
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- Prodrugs of compounds that inhibit TRPV1 receptor
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Compounds of formula (I) wherein A, R1, R2, and R3 are defined in the specification, and which are useful as therapeutic compounds particularly for treating disorders or conditions associated with inflammation, pain, bladd
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Page/Page column 28
(2010/11/27)
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- Development of a large scale asymmetric synthesis of vanilloid receptor (TRPV1) antagonist ABT-102
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A highly efficient asymmetric synthesis of TRPV1 antagonist ABT-102 was developed and successfully demonstrated on a multi-kilogram scale. This process incorporates a new asymmetric synthesis of (R)-tert-butylaminoindan, which is based on a chiral auxiliary induced diastereoselective reduction of its iminoindan precursor.
- Lukin, Kirill,Hsu, Margaret C.,Chambournier, Gilles,Kotecki, Brian,Venkatramani,Leanna
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p. 578 - 584
(2012/12/31)
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- Fused compounds that inhibit vanilloid receptor subtype 1 (VR1) receptor
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Compounds of formula (I) are novel VR1 antagonists that are useful in treating pain, inflammatory thermal hyperalgesia, urinary incontinence, or bladder overactivity.
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