Syntheses and in vitro evaluation of 4-(2-aminoethyl)-2(3H)-indolones and related compounds as peripheral prejunctional dopamine receptor agonists.
A series of (beta-aminoethyl)indolones and related compounds was synthesized and evaluated in vitro as peripheral prejunctional dopaminergic agonists in the field-stimulated isolated perfused rabbit ear artery. 4-[2-(Di-n-propylamino)ethyl]-7-hydroxy-2(3H)-indolone was the most potent compound (ED50 = 2 +/- 0.3 nM) tested, while the related secondary amine 24 and the des-OH derivatives 28 and 34 were only slightly less potent. 4-Methoxybenzeneethanamine and 2-methyl-3-nitrophenylacetic acid were employed as starting materials for for the synthesis of the 4-(beta-aminoethyl)indolones. The ring-opened 3-acylamino analogues 46 and 47 were prepared via nitration of the phenethylamine 43 derived from 4-methoxyphenylacetic acid. The inactive isomeric indolones 38, 39, and 41 were derived from 4-nitrobenzeneethanamine and from indolone-6-acetic acid.
R M
RM
DeMarinis
G
G
Gallagher
R F
RF
Hall
R G
RG
Franz
C
C
Webster
W F
WF
Huffman
M S
MS
Schwartz
C
C
Kaiser
S T
ST
Ross
J W
JW
Wilson
D000818:Animals; D001158:Arteries / Q000187:drug effects; D004423:Ear / Q000098:blood supply; D006830:Hydralazine / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects*; D013329:Structure-Activity Relationship
D007211:Indoles; D011724:Pyridazines; D011954:Receptors, Dopamine; D006830:Hydralazine