Discovery of potent,selective, and orally bioavailable PDE5 inhibitor: Methyl-4-(3-chloro-4-methoxybenzylamino)-8-(2-hydroxyethyl)-7-methoxyquinazolin-6-ylmethylcarbamate (CKD 533) |
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| Authors: | Hojin Choi Jaekwang Lee Young Hoon Kim Dai Sig Im In-Chang Hwang Soo Jin Kim Seung Kee Moon Hong Woo Lee Sung Sook Lee Soon Kil Ahn Sang Woong Kim Nam Song Choi Kyung Joo Lee |
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| Institution: | 1. Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., PO Box 74, Chonan, Republic of Korea;2. Department of Chemistry, Soong Sil University, Seoul 156-743, Republic of Korea;3. LeadGenex, Venture Town Dasan, 1687-2 Shinil-dong, Daedeok-gu, Daejeon, Republic of Korea |
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| Abstract: | In a continuing effort to discover novel PDE5 inhibitors, we have successfully found quinazolines with 4-benzylamino substitution as potent and selective PDE5 inhibitors. Initial lead compound (1) was found to be easily metabolized when incubated with human liver microsomes mainly through C6 amide hydrolysis. Blocking of this metabolic hot spot led to discovery of 10 (CKD533) which is highly potent, selective and orally efficacious in conscious rabbit model for erectile dysfunction and now is undergoing preclinical toxicology study. |
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