Structure-activity relationships among di- and tetramine disulfides related to benextramine.
The synthesis and irreversible alpha-blocking activity in the rat vas deferens of a series of tetra- and diamine disulfides 2-38, structural analogues of benextramine (BHC), are described. All compounds containing a central cystamine moiety displayed an irreversible alpha-adrenergic blockade at concentrations ranging from 10(-4) to 6 X 10(-6)M. Potency was increased in cystamines N,N'-disubstituted with 6-aminohexyl groups, especially when the outer nitrogen atoms bear arylalkyl substituents or are enclosed in a ring. However, N,N,N',N'-tetrasubstituted cystamines were poor blockers. Structural specificity in the outer portion of the tetramine disulfide is low, since many types of substituents gave rise to potent alpha-blockers. Even replacement of the outer amines with nonbasic ethers or amides was observed to maintain irreversible alpha-blockade.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D003538:Cystamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004220:Disulfides / Q000138:chemical synthesis / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000317:Adrenergic alpha-Antagonists; D004220:Disulfides; C029998:benextramine; D003538:Cystamine; D009638:Norepinephrine