Potent anticonflict activity and lessening of memory impairment with a series of novel [1]benzothieno[2,3-c]pyridines and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines

Abstract

[1]Benzothieno[2,3-c]pyridines (10a-c, 11, 12a-t, and 13a,b) and 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridines (3a-c, 7, 8a-c, and 9) were synthesized. The compounds are bioisosteres of beta-carbolines and 1,2,3,4-tetrahydro-beta-carbolines where the indole nitrogen is replaced by sulfur. Their pharmacological activity was evaluated in a water lick conflict test in rats and a passive avoidance test in mice. In the 1,2,3,4-tetrahydro[1]benzothieno[2,3-c]pyridine series, the presence of ethyl ester (3b) or cyclohexyl carboxamide (7) groups at C-3 conferred good anticonflict activity and lessening of memory impairment, while N-acylation of 3b abolished activity. In the [1]benzothieno(2,3-c]pyridine series, the aminoethyl carboxamide (12a) group at C-3 also conferred activity, but other amides studied were not active. The most potent compounds (3b, 7, and 12a) were also administered orally and had potent anticonflict and antiscopolamine amnesia-reversal activity. These compounds did not bind to the BZP receptor in spite of having structures similar to those of beta-carbolines. Compound 7 bound strongly to 5-HT1A receptors and would be expected to be a novel anxiolytic.

Enantio- and Chemoselective Intramolecular Iridium-Catalyzed O-Allylation of Oximes

“…To this end, γ-hydroxy thienyl oxime 1c was chosen as a starting point for the preparation of diverse enantioenriched building blocks (Scheme A). The rhodium-catalyzed and oxime-directed C–H activation of enantioenriched ( S )- 1c furnished thienopyridine 4 , a promising motif in drug discovery, without any erosion of the optical purity. The lithiation of dihydrooxazine 3c and subsequent trapping with allyl bromide allowed the selective installation of an additional stereocenter ( 5 ), showcasing the applicability of the method for the synthesis of highly substituted heterocycles.…”

Dialkylaminoacetonitrile Derivatives as Amide Synthons. A One-Pot Preparation of Heteroaryl Amides via a Strategy of Sequential SNAr Substitution and Oxidation

“…Heteroaryl amides are both useful synthetic intermediates and important structural elements of several drugs and candidates, including the hypnotic agent rilmazafone and the HIV non-nucleoside reverse transcriptase inhibitor delavirdine (Figure ). , We have previously demonstrated that N,N-disubstituted aminoacetonitrile derivatives ( 1 ) are effective synthons of the corresponding amides 2 via a procedure that takes advantage of umpolung-like properties of 1 , as summarized in Figure . The anion of 1 , prepared by deprotonation using NaHDMS in THF, was reacted with an ester 3 to provide intermediate 4 (Scheme ).…”