- PROCESSES FOR THE PREPARATION OF 3,4-SUBSTITUTED-1,2,5-THIADIAZOLES AND INTERMEDIATES THEREOF
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The present invention relates to intermediate compounds useful for the preparation of 1,2,5-thiadiazole compounds, including unsymmetrically substituted compounds such as 4-(3-secondary amino-2-hydroxy-propoxy)-1,2,5-thiadiazole compounds and azacyclic or azabicyclic 1,2,5-thiadiazole compounds and to processes for making the same.
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Page/Page column 9
(2009/07/03)
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- (Acyloxy)alkyl Carbamates as Novel Bioreversible Prodrugs for Amines: Increased Permeation through Biological Membranes
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(Acyloxy)alkyl carbamates of the type R1R2N-CO-O-CHR3-OCO-R4 are described as novel bioreversible prodrugs for primary and secondary amines.These were prepared either by a one-step reaction involving nucleophilic attack on p-nitrophenyl α-(acyloxy)alkyl carbonates with displacement of p-nitrophenol or by reaction of α-haloalkyl carbamates with silver or mercury salts of carboxylic acids.Enzymatic hydrolysis of the ester bond in these ester carbamates leads to a cascade reaction resulting in rapid regeneration of the parent amine.Permeability measurements of such nonionic derivatives of atenolol, betaxolol, pindolol, propranolol, and timolol through fuzzy rat skin and rabbit cornea mounted on diffusion cells show that derivatization of the hydrophilic β-blockers results in several-fold increase in permeation through these biological membranes.However, prodrug modification of the lipophilic β-blockers leads to little advantage in permeability characteristics.
- Alexander, Jose,Cargill, Robyn,Michelson, Stuart R.,Schwam, Harvey
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p. 318 - 322
(2007/10/02)
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- Novel methods and compounds employed therein
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Preparation of an optically active alkamine in the sinister configuration, or a derivative of said alkamine, which is reacted with an 3-X-4-chloro(or RO-- where R is hydrogen or an alkali metal)-1,2,5-thiadiazole to prepare S-3-X-4-(3-substituted amino-2-hydroxypropoxy)-1,2,5-thiadiazole beta adrenergic blocking agents. Novel 3-morpholino-4-chloro(or RO--)-1,2,5-thiadiazoles and their preparation also are described.
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