Synthesis and evaluation of N,N-di-n-propyltetrahydrobenz[f]indol-7-amine and related congeners as dopaminergic agonists

Abstract

An evaluation of 6-[2-(di-n-propylamino)ethyl]indole (4), its rigid analogue N,N-di-n-propyl-5,6,7,8-tetrahydrobenz[f]indol-7-amine (5), and some related congeners, for ability to suppress serum prolactin in reserpinized rats, revealed modest biological activity in this in vivo model of dopaminergic activity. Although the indole N-H in these compounds can be considered to be oriented "meta" with respect to the ethylamine side chain, compounds with the indole N-H located in the other "meta" position (i.e. 4-[2-(di-n-propylamino)ethyl]indole (2) or its rigid benz[e]indole analogue 3) were much more potent dopamine agonists. The results argue for a particular orientation of the indole N-H vector. In addition, relatively potent dopamine agonists also resulted when the pyrrole portion of the indole ring was replaced by a methanesulfonamido function, supporting the idea that the indole N-H serves as a hydrogen-bond donor.

Transition State Imbalance in the Deprotonation of Substituted 2-Tetralones by Hydroxide Ion

“…7-Nitro-2-tetralone (1e) eluted as a second major product and was recrystallized from ethyl acetate/hexane (370 mg, 40%), mp 97−98 °C (lit. 16a,b 94−96 °C; 96−97 °C). TLC (hexane/ethyl acetate, 2:1), R f = 0.32.…”

Synthesis and dehydration reaction of 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,2,3,4-tetrahydronaphth-2-ol: possible intermediate of Lasofoxifene

“…In this case, a practically quantitative yield of the required 7b-[4-(benzyloxy)phenyl]-5-methoxy-1a,2,3,7b-tetrahydronaphtho[1,2-b]oxirane (4) was achieved. The subsequent isomerization of pure epoxide 4 to tetralone 5 was performed with the catalysis [10][11][12] by ZnI 2 (75%). The next reaction step was the reaction of phenylmagnesium bromide with tetralone 5, which gave 1-(4-benzyloxyphenyl)-6-methoxy-2-phenyl-1,2,3,4-tetrahydro-2-naphthol (2) (87%).…”

Design and synthesis of a bivalent ligand to explore the putative heterodimerization of the mu opioid receptor and the chemokine receptor CCR5

“…However, Boc group may be sensitive to such acidic conditions. Replacement of BH 3 ·THF with LiAlH 4 , which only needs water to decompose the intermediate formed after the reaction, 47 provided 7 in a reasonable yield (Scheme 2). Reaction of 7 with 4,4-difluorocyclohexanecarboxylic acid 48 8 was mediated by HOBt/EDCI and the coupling product 20 was subsequently converted to the CCR5 antagonist precursor 6 with TFA/DCM (1:10) at ambient temperature 49 (Scheme 3).…”