Design and synthesis of novel dihydropyridine alpha-1a antagonists.
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.
Marzabadi
M R
MR
Department of Chemistry, Synaptic Pharmaceutical Corporation, Paramus, NJ 07652, USA.
Hong
X
X
Nagarathnam
D
D
Miao
S W
SW
Chiu
G
G
Wong
W C
WC
Wetzel
J M
JM
Fang
J
J
Forray
C
C
Chen
T B
TB
O'Malley
S S
SS
Chang
R S
RS
Gluchowski
C
C
D018674:Adrenergic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D015220:Calcium Channels / Q000378:metabolism; D004095:Dihydropyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D004285:Dogs; D006801:Humans; D008297:Male; D015394:Molecular Structure; D010656:Phenylephrine / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects; D011470:Prostatic Hyperplasia / Q000188:drug therapy; D011485:Protein Binding; D051381:Rats; D013237:Stereoisomerism
D018674:Adrenergic Antagonists; D015220:Calcium Channels; D004095:Dihydropyridines; D010656:Phenylephrine