2-(Aminomethyl)phenols, a new class of saluretic agents. 1. Effects of nuclear substitution

Abstract

A series of 2-(aminomethyl)phenols was synthesized and tested in rats and dogs for saluretic and diuretic activity. A number of these compounds exhibit a high order of activity on iv or po administration. The most active compounds belong to a subseries of 4-alkyl-6-halo derivatives of which 2, 2-(aminomethyl)-4-(1,1-dimethylethyl)-6-iodophenol, is the most active. Compound 2 also possesses significant antihypertensive activity, an adjunctive pharmacological parameter which distinguishes 2 from the other compounds prepared in this series. In addition, 2 displays both topical saluretic and antiinflammatory activities.

Synthesis of microtubule-interfering halogenated noscapine analogs that perturb mitosis in cancer cells followed by cell death

“…Chlorination of noscapine using sulfuryl chloride in chloroform at low temperature gave excellent yields and the desired regioselectivity. Using this method, 9-Cl-nos (4) was obtained in 90% yield (Scheme 1) [35]. The chlorination took place chemoselectively on ring A of isoquinoline nucleus at position C-9.…”

Adenosine Analogues as Selective Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase of Trypanosomatidae via Structure-Based Drug Design

“…28,33,34 2-Naphthalenemethylamine hydrochloride (51), 4-methoxy-1-naphthalenemethylamine hydrochloride (55), and 3-methoxy-1-naphthalenemethylamine hydrochloride (57) were prepared by LiAlH 4 reduction of 2-naphthonitrile (50), 35 4-methoxy-1-naphthonitrile (54), and 3-methoxy-1-naphthonitrile (56), 36 respectively. By use of the methodology of Deana et al 37,38 for the synthesis of 2-hydroxy-1-naphthalenemethylamine, 2-methoxy-1-naphthalenemethylamine (53) was prepared by treatment of 2-methoxynaphthalene (52) with 2-chloro-N-(hydroxymethyl)acetamide and hydrochloric acid. 3-Hydroxy-1-naphthalenemethylamine hydrobromide (58) was prepared by treatment of 57 with BBr 3 (Scheme 4).…”

Rational Design of the Microtubule-Targeting Anti–Breast Cancer Drug EM015

“…EM015 was prepared under mild conditions by aromatic halogenation of noscapine using sulfuryl chloride in chloroform at 25jC yielding the desired compound (ref. 28; Fig. 1B).…”

“…chloroform (100 mL) to a solution of 12.01 mmol/L noscapine in chloroform (200 mL) and stirred for 10 hours at 25jC until subjected to TLC (7% methanol in chloroform; ref. 28). On completion of the reaction, the mixture was poured into 300 mL of water and extracted with chloroform twice.…”