Design and synthesis of novel dihydropyridine alpha-1a antagonists

M R Marzabadi; X Hong; D Nagarathnam; S W Miao; G Chiu; W C Wong; J M Wetzel; J Fang; C Forray; T B Chen; S S O'Malley; R S Chang; C Gluchowski

doi:10.1016/s0960-894x(99)00484-9

Design and synthesis of novel dihydropyridine alpha-1a antagonists

Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8. doi: 10.1016/s0960-894x(99)00484-9.

Authors

M R Marzabadi¹, X Hong, D Nagarathnam, S W Miao, G Chiu, W C Wong, J M Wetzel, J Fang, C Forray, T B Chen, S S O'Malley, R S Chang, C Gluchowski

Affiliation

¹ Department of Chemistry, Synaptic Pharmaceutical Corporation, Paramus, NJ 07652, USA.

PMID: 10522703
DOI: 10.1016/s0960-894x(99)00484-9

Abstract

A series of analogs of SNAP 5150 containing heteroatoms at C2 or C6 positions is described. Herein, we report that the presence of alkyl substituted heteroatoms at the C2(6)-positions of the dihydropyridine are well tolerated. In addition, 15 inhibited the phenylephrine induced contraction of dog prostate tissue with a Kb of 1.5 nM and showed a Kb (DBP, dogs, microg/kg)/Kb (IUP, dogs, microg/kg) ratio of 14.8/2.5.

MeSH terms

Adrenergic Antagonists / chemical synthesis*
Adrenergic Antagonists / pharmacology
Animals
Calcium Channels / metabolism
Dihydropyridines / chemical synthesis*
Dihydropyridines / pharmacology
Dogs
Humans
Male
Molecular Structure
Phenylephrine / pharmacology
Prostate / drug effects
Prostatic Hyperplasia / drug therapy
Protein Binding
Rats
Stereoisomerism

Substances

Adrenergic Antagonists
Calcium Channels
Dihydropyridines
Phenylephrine