3-Thio-quinolinone maxi-K openers for the treatment of erectile dysfunction

Bioorganic and Medicinal Chemistry Letters

Volumn 14, Issue 20, 2004, Pages 5089-5093

  Boy, Kenneth M ^a   Guernon, Jason M ^a   Sit, Sing Yuen ^a   Xie, Kai ^a   Hewawasam, Piyasena ^a   Boissard, Christopher G ^a   Dworetzky, Steven I ^a   Natale, Joanne ^a   Gribkoff, Valentin K ^a   Lodge, Nicholas ^a   Starrett Jr , John E ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

BK; Erectile dysfunction; Maxi K; Potassium channels

Indexed keywords

QUINOLINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CHANNEL GATING; CONTROLLED STUDY; CORPUS CAVERNOSUM; DRUG SYNTHESIS; ERECTILE DYSFUNCTION; GENETIC TRANSFECTION; MALE; NONHUMAN; OOCYTE; RABBIT;

ORYCTOLAGUS CUNICULUS;

EID: 4544335749     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2004.07.080     Document Type: Article

References (11)

1. V.K. Gribkoff, J.E. Starrett Jr., and S.I. Dworetzky Neuroscientist 7 2001 166 177
2. V.P. Korovkina, and S.K. England Clin. Exp. Pharmacol. Physiol. 29 2002 317 323
3. A. Marty Trends Neurosci. 12 1989 33 40
4. R.B. Moreland, G. Hsieh, M. Nakane, and J.D. Brioni J. Pharmacol. Exp. Ther. 296 2001 225 234
5. S. Mariya, R. Rodriguez, R.S. Rosenbaum, H.-Z. Wang, M. Arnold, and G.J. Christ J. Urol. 167 2002 2628 2635
6. P. Hewawasam, W. Fan, J. Knipe, S.L. Moon, C.G. Boissard, V.K. Gribkoff, and J.E. Starrett Bioorg. Med. Chem. Lett. 12 2002 1779 1783
7. P. Hewawasam, W. Fan, M. Ding, K. Flint, D. Cook, G.D. Goggins, R.A. Myers, V.K. Gribkoff, C.G. Boissard, S.I. Dworetzky, J.E. Starrett, and N.J. Lodge J. Med. Chem. 46 2003 2819 2822
8. Hewawasam, P.; Starrett, Jr. J. E. U.S. Patent 6,184,231, 2001
9. V.K. Gribkoff, J.T. Lum-Ragan, C.G. Boissard, D.J. Post-Munson, N.A. Meanwell, J.E. Starrett, E.S. Kozlowski, J.L. Romine, and J.T. Trojnacki Mol. Pharmacol. 50 1996 206 217
10. For comparison, 4-(5-chloro-2-hydroxyphenyl)-3-(2-hydroxyethyl)-6- (trifluoromethyl)quinolin-2(1H)-one was measured to have a 378% ± 35 increase over control in oocytes, and a 83.7% ± 11.0 inhibition of force in rabbit corpus cavernosum (compd 11b in P. Hewawasam, W. Fan, M. Ding, K. Flint, D. Cook, G.D. Goggins, R.A. Myers, V.K. Gribkoff, C.G. Boissard, S.I. Dworetzky, J.E. Starrett, and N.J. Lodge J. Med. Chem. 46 2003 2819 2822
11. n's were typically 3-4; if needed, additional n's were added such that SEM's were less than 10% of the reported value