16187-91-0

Upstream product

• 16187-90-9 β-imino-β-phenylpropionitrile 
• 1823-99-0 3-amino-3-phenylacrylonitrile 

Downstream Products

• 16188-24-2 3-(2,4-dichloro-phenyl)-5-methyl-isothiazole-4-carboxylic acid 
• 16188-23-1 3-(2,4-dichloro-phenyl)-5-methyl-isothiazole-4-carbonitrile 
• 16188-02-6 3-(4-chloro-phenyl)-5-methyl-isothiazole-4-carboxylic acid 
• 16188-01-5 3-(4-chloro-phenyl)-5-methyl-isothiazole-4-carbonitrile 
• 16187-97-6 5-methyl-3-phenyl-isothiazole-4-carboxylic acid amide 
• 13369-71-6 3-phenyl-5-methylisothiazole 
• 13950-63-5 5-methyl-3-phenyl-4-isothiazolecarbonitrile 
• 13950-68-0 4-cyano-3-phenylisothiazole 
• 13363-69-4 3-phenyl-1,2-thiazole-5-carboxylic acid 
• 14208-30-1 3-phenyl-isothiazole-5-carbonitrile 
• 10514-34-8 3-phenylisothiazole 
• 19762-79-9 3-(4-bromo-phenyl)-5-methyl-isothiazole-4-carbonitrile 
• 19762-89-1 5-methyl-3-(2,4,5-trichloro-phenyl)-isothiazole-4-carboxylic acid 
• 19762-78-8 5-methyl-3-(2,4,5-trichloro-phenyl)-isothiazole-4-carbonitrile 

Relevant academic research and scientific papers

Pyrimidine benzamide-based thrombopoietin receptor agonists

A series of pyrimidine benzamide-based thrombopoietin receptor agonists is described. The lead molecule contains a 2-amino-5-unsubstituted thiazole, a group that has been associated with idiosyncratic toxicity. The potential for metabolic oxidation at C-5 of the thiazole, the likely source of toxic metabolites, was removed by substitution at C-5 or by replacing the thiazole with a thiadiazole. Potency in the series was improved by modifying the substituents on the pyrimidine and/or on the thiazole or thiadiazole pendant aryl ring. In vivo examination revealed that compounds from the series are not highly bioavailable. This is attributed to low solubility and poor permeability.

Phototransposition chemistry of phenylisothiazoles and phenylthiazoles. 1. Interconversions in benzene solution

Phenylthiazoles 1-3 and phenylisothiazoles 4-6 undergo phototransposition in benzene solvent mainly by P5, P6, and P7 permutation pathways. Phenylisothiazoles 5 and 6 also transpose via a P4 permutation process to yield phenylthiazoles 2 and 3 in less than 1% yield. In benzene saturated with D2O, 2-phenylthiazole (1) and 5-phenylisothiazole (6) each phototranspose to yield 4-deuterio-3-phenylisothiazole (4-D-4) and 4-phenylthiazole (2) without deuterium incorporation. Irradiation of 4-phenylthiazole (2) under these conditions results in rapid photodeuteration to yield 2-deuterio-4-phenylthiazole (2-D-2), which subsequently phototransposes to 5-deuterio-3-phenylisothiazole (5-D-3). These experimental results can be rationalized by a mechanism involving initial electrocyclic ring closure and sigmatropic shift of sulfur around the four sides of the azetine ring. Rearomatization of each bicyclic intermediate thus allows sulfur to insert into each position in the carbon-nitrogen sequence. As a consequence, these compounds divide into a tetrad in which isomers 1, 2,4, and 6 interconvert mainly via P5, P6, and P7 pathways and a dyad of two compounds in which 3 phototransposes to 5 via P5 and P7 pathways. Within the tetrad, BC-6, the bicyclic intermediate derived from 5-phenylisothiazoles (6), is postulated to undergo deuteration with simultaneous sigmatropic shift of sulfur when the reaction is carried out in benzene-D2O. This mechanistic view provides one coherent interpretation for the observed phototransposition and photodeuteration reactions.