Synthesis of New Indole and Adamantane Amido Derivatives with Pharmacological Interest

Abstract

The synthesis and preliminary pharmacological evaluation of new indole and adamantane amido derivatives is described. The design was based on the pharmacophoric properties of 4‐{4‐[4‐(trifluoromethoxy)phenoxy]piperidin‐1‐yl), 6‐[4‐(trifluoro methoxy)phenyl]pyridin‐3‐yl and 4‐(trifluoro)phenyl tails, which are present as side chains in the structures of promising drug candidates, currently in clinical tests. These pharmacophores were incorporated into the indole and adamantane scaffolds, respectively. The new derivatives were evaluated for their antimycobacterial potential. The following amides, N‐[2‐(5‐methoxy‐1H‐indol‐3‐yl)ethyl]‐4‐{4‐[4(trifluoromethoxy)phenoxy]piperidin‐1‐yl}benzamide (1 b) and N‐{4‐[4‐(4‐(trifluoromethoxy)phenoxy)piperidin‐1‐yl]benzyl}‐1H‐indolyl‐2‐carboxamide (2 b), are endowed with antitubercular properties, which merit further investigation.

Synthesis and evaluation of novel 2,4-disubstituted arylthiazoles against T. brucei

“…Elution with 20% EtOAc in hexanes afforded compound 2h as a white solid (100 mg, 65%). 1 2-Bromo-1-[4-(1-Tricycloij3.3.1.1 3,7 ]decyl)phenyl]ethanone (19). To a stirred solution of (1-phenyl)adamantane (18) 35 (1.00 g, 4.71 mmol) and AlCl 3 (700 mg, 5.10 mmol) in anhydrous DCM (10 mL) was added a solution of BrCOCH 2 Br (0.5 mL, 4.71 mmol) in anhydrous DCM (10 mL) under an argon atmosphere, at −10°C.…”

“…1, as potent trypanocidals. 6,7 Based on these findings and our involvement in the adamantane chemistry, [9][10][11][12][13][14][15][16][17][18][19][20] we report herein on the chemistry and biology of thiazole derivatives of the general type scaffold IV. The thiazole moiety is an important pharmacophore in many compounds used against several tropical infectious diseases.…”

Design, Synthesis and in vitro Controlled Release of New Adamantanodiarylketone Antimycobacterials

“…For over a decade, we have been interested in adamantane chemistry in an attempt to exploit adamantane's role in a variety of pharmacological activities . Recently, we have been involved with the synthesis of adamantane derivatives with antimycobacterial activity . The adamantane core enhances the lipophilicity of the derivatives, where is present, and acts on the mycobacterial wall .…”

“…[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] Recently, we have been involved with the synthesis of adamantane derivatives with antimycobacterial activity. [24][25][26][27][28][29] The adamantane core enhances the lipophilicity of the derivatives, where is present, and acts on the mycobacterial wall. [30,31] Following this work, we now describe the preparation of three substituted adamantane diarylketones A, B and C, shown in Figure 2.…”