Synthesis and evaluation of pyridazinylpiperazines as vanilloid receptor 1 antagonists

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 22, 2004, Pages 5513-5519

  Tafesse, Laykea ^a   Sun, Qun ^a   Schmid, Lori ^a   Valenzano, Kenneth J ^a   Rotshteyn, Yakov ^a   Su, Xin ^a   Kyle, Donald J ^a  

^a PURDUE PHARMA L P   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

N (4 TERT BUTYLPHENYL) 4 (3 CHLOROPYRIDIN 2 YL)TETRAHYDROPYRAZINE 1(2H) CARBOXAMIDE; PIPERAZINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG ACTIVITY; DRUG POTENCY; DRUG STRUCTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; PH MEASUREMENT;

ANIMALS; CELL LINE; DRUG EVALUATION, PRECLINICAL; HUMANS; MOLECULAR STRUCTURE; PIPERAZINES; PYRAZINES; PYRIDAZINES; PYRIDINES; RECEPTORS, DRUG; TIME FACTORS; TRPV CATION CHANNELS;

EID: 5144232587     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.09.010     Document Type: Article

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29. 16
30. 3CN)
31. 3): δ 8.84 (br s, 1H), 7.61-7.53 (m, 1H), 7.49-7.42 (m, 1H), 7.25-7.21 (m, 1H), 7.16-7.07 (m, 1H), 4.54-4.43 (m, 1H), 4.08 (br d, 1H, J = 12.93 Hz), 3.64-3.56 (m, 1H), 3.54-3.37 (m, 2H), 3.23 (dd, 1H, J = 3.73 Hz, J = 12.49 Hz), 3.11 (dt, 1H, J = 3.51 Hz, J = 12.71 Hz), 2.34 (br d, 3H, J = 0.44 Hz), 1.44 (d, 3H, J = 6.79 Hz)
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33. The assays were conducted on hERG channel expressed in HEK-293 cells (obtained from Wisconsin Alumni Research Foundation) at 1 μM concentration using a standard whole cell voltage-clamp protocol, that is, pre-pulsing from -80 mV to +20 mV for 2 s and then pulsing to -40 mV for 1 s every 15 s. The peak amplitude of the tail current elicited by the second, test, pulse was used to assess the degree of inhibition. Percent inhibition was measured at least in three cells for each compound, with astemizole, 100 nM as a positive control; data is presented as mean ± SEM