ISSN:
0018-019X
Keywords:
Chemistry
;
Organic Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
A series of 5-substituted (-)-(S)-N-[(1-ethylpyrrolidin-2-yl)methyl]-2,3-diniethoxybenzanndes were made by reaction of the corresponding benzoyl chlorides with (S)-1-ethylpyrrolidine-2-methylaruine (→ 14-16, 18-21). The acids required were prepared in a regiospecific manner from 5-bromo-2,3-dimethoxybenzoic acid which was protected as dihydrooxazole (→ 4-8), metalated, reacted with various electrophiles (MeI, EtI, BuBr, CC13CCl3 or MeSSMe), and hydrolyzed (→9-13). Alternatively, (-)-(S)-5-bromo-N-[(1-ethylpyrrolidin-2-yl)methyl]-2,3-di-methoxybenzamide was treated with KH followed by BuLi and an electrophile (I2 or Me3SiCl) to give the 5-iodo and 5-(trimethylsilyl) derivatives 17 and 22, respectively. All 5-substituted amides were highly potent inhibitors of [3H]spiperone binding in rat striatal membranes with IC50 values of 0.5 to 5 nM (Table 3). Thus, a relatively large steric bulk can be accomodated in the position para to the 2-MeO group. This work also supports the notion that a positive as well as negative electrostatic potential can be located in this position. A selected number of derivatives were also investigated in vivo and found to inhibit apomorphine-induced behavioural responses in the same dose range as haloperidol and raclopride (Table 4). This new group of benzamides is suitable for investigations of dopamine D-2 receptors in labelled or unlabelled form.
Additional Material:
4 Tab.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/hlca.19900730221
Permalink
