Dog coronary artery adenosine receptor: structure of the N6-alkyl subregion.
J Med Chem
; 28(11): 1636-43, 1985 Nov.
Article
in En
| MEDLINE
| ID: mdl-2999397
ABSTRACT
The moderately potent and stereoselective coronary vasoactivity of N6-[1-phenyl-2(R)-propyl]adenosine (1) is the basis for the present study that maps the N6 region of the coronary artery adenosine receptor by means of the structure-coronary vasoactivity relationships of 81 analogues of 1 in the open-thorax dog. Stereoselectivity is a general property of N6-substituted adenosines that have a chiral center adjacent to N6. The activity ratio of 1 to its S diastereomer is 10, the result of the positive interaction with the receptor of the propyl C-3 group of the R diastereomer in combination with the steric hindrance exerted by this group of the S diastereomer. Replacing the benzyl moiety of 1 by an ethyl, phenyl, phenethyl, or naphthyl group lowers potency of the R diastereomer and, accordingly, the R/S ratio. Propyl C-1 of 1 interacts with a receptor region large enough to accommodate three methylene residues and the propyl C-3 residue with a separate region large enough to accommodate two. The receptor subregion that interacts with the propyl C-1 of 1 is more tolerant of bulk and of polar substituents than the subregion that interacts with propyl C-3. Evidence bearing on the possible contribution of N6 to activity, e.g. through hydrogen bonding, is ambiguous. These results support a provisional model of the N6-alkyl subregion.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Adenosine
/
Receptors, Cell Surface
/
Coronary Vessels
Limits:
Animals
Language:
En
Journal:
J Med Chem
Journal subject:
QUIMICA
Year:
1985
Type:
Article