Seetharamaiyer Padmanabhan

Asymmetric synthesis of a neuroprotective and orally active N-methyl-d-aspartate receptor ion-channel blocker, CNS 5788

Abstract Asymmetric synthesis of N -(2-chloro-5-methylthiophenyl)- N′ -(3-methylsulfinylphenyl)- N′ -methylguanidine (CNS 5788) was achieved in high enantiomeric excess through condensation of the cyanamide derivative, 6 and the sulfinylaniline hydrochloride, 5 . The key step involved the asymmetric oxidation of N -methyl-3-methylthioaniline using a Davis reagent.

A Convenient One Pot Procedure for N-Methylation of Aromatic Amines Using Trimethyl Orthoformate

Abstract Aromatic amines react with trimethyl orthoformate in the presence of concentrated sulfuric acid followed by acid hydrolysis to afford mono methylated amines in moderate to good yields.

Solution-phase, parallel synthesis and pharmacological evaluation of acylguanidine derivatives as potential sodium channel blockers.

Solution-phase synthesis of various acylguanidine derivatives and the evaluation of a small library of compounds as potential sodium channel blockers are described.

Formation of Chromenes and Coumarin Derivatives From Salicylaldehydes and 2-Pentenedioate: Facile Route to 3-Formylcoumarins

Abstract Condensation of salicylaldehydes with diethyl 2-pentenedioate under the Knoevenagel conditions afforded either coumarin-3-acrylates or 2H-chromenedicarboxylate derivatives depending on the substituents on the aryl nucleus. Osmium tetroxide catalyzed periodate oxidation of coumarin-3-acrylates gave 3-formylcoumarin derivatives.

Reaction of Iodoarenes and Diethyl 2-Pentenedicarboxylate Under the Heck Reaction Conditions. Formation of 3-Aryl-2-pentenedicarboxylates

Abstract Various substituted iodoarenes underwent arylation with diethyl 2-pentenedicarboxylate under the Heck reaction conditions to give the expected diethyl 3-aryl-2-pentenedicarboxylates. Extension of this reaction to 2-iodoaniline gave the hitherto unreported ethyl quinolin-2-one-4-acetate.

Identification and characterization of a potential ischemia-selective N-methyl-D-aspartate (NMDA) receptor ion-channel blocker, CNS 5788.

The identification and characterization of a potentially ischemia-selective and orally-active sulfoxide based NMDA ion-channel blocker showing good neuroprotective activity, (R)-(+)-N-(2-chloro-5-methylthiophenyl)-N-(3-methylsulfinylphenyl)-N-methylguanidine (CNS 5788), is described.

A GENERAL PROCEDURE FOR THE SYNTHESIS OF ACYLGUANIDINES DERIVED FROM ALIPHATIC AND AROMATIC AMINES

Condensation of aliphatic and aromatic amines with 1-aroyl- S-methylisothiourea in the presence of triethylamine affords acylguanidines in moderate to good yields. An improved procedure for the generation of 1-aroyl-S-methylisothiourea derivatives is described.

Formation of Chromene Analogs of Homophthalates: Investigation of Condensation Products Derived from 2-Hydroxybenzaldehydes and Diethyl 2-Pentenedicarboxylates

Abstract Condensation of substituted 2-hydroxybenzaldehyde derivatives (1a-1) with diethyl 2-pentenedicarboxylate (2) in the presence of piperidine gave coumarin and / or chromene derivatives. Attempted reaction of 4-N,N-diethylamino-2-hydroxybenzaldehyde (1a) and 2-hydroxy-3-nitrobenzaldehyde (1i) with diethyl 3-phenyl-2-pentenedicarboxylate (5) led to formation of no coumarin or chromene derivative.