Design of potent, orally available antagonists of the transient receptor potential vanilloid 1. Structure-activity relationships of 2-piperazin-1-yl-1H- benzimidazoles

Journal of Medicinal Chemistry

Volumn 49, Issue 12, 2006, Pages 3719-3742

  Ognyanov, Vassil I ^a   Balan, Chenera ^a   Bannon, Anthony W ^a   Bo, Yunxin ^a   Dominguez, Celia ^a   Fotsch, Christopher ^a   Gore, Vijay K ^a   Klionsky, Lana ^a   Ma, Vu V ^a   Qian, Yi Xin ^a   Tamir, Rami ^a   Wang, Xianghong ^a   Xi, Ning ^a   Xu, Shimin ^a   Zhu, Dawn ^a   Gavva, Narender R ^a   Treanor, James J S ^a   Norman, Mark H ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6 (3,4 DIFLUOROPHENYL) 2 [4 [3 (TRIFLUOROMETHYL)PYRIDIN 2 YL]PIPERAZIN 1 YL] 1H BENZO[D]IMIDAZOLE; BENZIMIDAZOLE DERIVATIVE; CAPSAICIN; CATION CHANNEL; FREUND ADJUVANT; MEMBRANE RECEPTOR; N [4 (TRIFLUOROMETHYL)BENZYL] 6 (TRIFLUOROMETHYL) 2 [4 [3 (TRIFLUOROMETHYL)PYRIDIN 2 YL]PIPERAZIN 1 YL] 1H BENZO[D]IMIDAZOL 5 AMINE; PIPERAZINE DERIVATIVE; RESINIFERATOXIN; TRANSIENT RECEPTOR POTENTIAL VANILLOID 1 ANTAGONIST; UNCLASSIFIED DRUG; VANILLOID RECEPTOR 1;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DISTRIBUTION VOLUME; DOSE RESPONSE; DRUG ABSORPTION; DRUG BINDING SITE; DRUG BIOAVAILABILITY; DRUG CLEARANCE; DRUG CONFORMATION; DRUG DESIGN; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; GENE EXPRESSION; HYPERALGESIA; IC 50; INFLAMMATION; MALE; NEUROPATHIC PAIN; NONHUMAN; PAIN; RAT; SENSORY STIMULATION; STEREOSPECIFICITY; STRUCTURE ACTIVITY RELATION;

ADMINISTRATION, ORAL; ANALGESICS; ANIMALS; BENZIMIDAZOLES; BIOLOGICAL AVAILABILITY; CALCIUM; CAPSAICIN; CHO CELLS; CRICETINAE; CRICETULUS; FREUND'S ADJUVANT; HEAT; HYDROGEN-ION CONCENTRATION; HYPERALGESIA; MALE; PAIN MEASUREMENT; PIPERAZINES; RATS; RATS, SPRAGUE-DAWLEY; RECOMBINANT PROTEINS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; TRPV CATION CHANNELS;

EID: 33745136758     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm060065y     Document Type: Article

References (46)

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45. All compounds were tested in a separate assay for agonist activity.
46. This result showing that the trifluoromethyl group is the most preferable substituent at position 3′ of the pyridine ring is consistent with that reported in ref 39b by Purdue Pharma researchers.