Schering Corporation

John J Wright

Alan K Mallams

Tattanahalli L Nagabhushan

Dinanath F Rane

Russell E Pike

Peter J Daniels

Alan B Cooper

Disclosed are triazolyl-substituted propane derivatives useful in the treatment of fungal diseases of humans and animals. Also disclosed are the processes for preparing the compounds, pharmaceutical compositions containing them, and the method of treating fungal diseases with said compounds.

Triazolyl-substituted propane derivatives

3-Aralkyloxy-2,3-dihydro-2-(triazolylmethyl)benzo(b)thiophenes and related derivatives having antifungal, antibacterial, and antiprotozoal activity are prepared by the reaction of the corresponding 2,3-dihydro-3-hydroxy-2-(triazolylmethyl)benzo(b)thiophene or related derivative and an aralkyl halide. Preferred compounds are those where the aralkyl function is a hetercyclic aromatic, particularly 2-chloro-3-thenyl, and where the benzene nucleus is substituted by chlorine or fluorine. Pharmaceutical formulations comprising compounds of this invention are described, as well as the method for their use in treating microbial infections.

3-Aralkyloxy-2,3-dihydro-2-(triazolymethyl)benzo(b)thiophenes

This invention relates to 2,3-dihydro-2-(imidazolylmethyl)benzo(b)thiophenes, to intermediates useful in their preparation, and to processes for preparing said intermediates. Also included in the invention are pharmaceutical compositions and the method of use of the compounds as antifungal agents.

2,3-Dihydro-2-(imidazolylmethyl)benzo(b)thiophenes

There is disclosed certain cyclopropyl substituted polyenes useful for treating dermatoses such as acne, psoriasis and epithelial cancers.

Cyclopropyl substituted polyenes

3-Aralkyloxy-2,3-dihydro-2-(imidazolylmethyl(benzo(b)thiophenes and related derivatives having antifungal, antibacterial, and antiprotozoal activity are prepared by the reaction of the corresponding 2,3-dihydro-3-hydroxy-2-(imidazolylmethyl)benzo(b)thiophene or related derivative and an aralkyl halide. Preferred compounds are those where the aralkyl function is a hetercyclic aromatic, particularly 2-chloro-3-thenyl, and where the benzene nucleus is substituted by chlorine or fluorine. Pharmaceutical formulations comprising compounds of this invention are described, as well as the method for their use in treating microbial infections.

3-Aralkyloxy-2,3-dihydro-2-(imidazolylmethyl)benzo(b)thiophenes and

This invention describes a novel process whereby 1,3'-di-N-unprotected-poly-N-protected-4,6-di-O-(aminoglycosyl)-1,3-diamin ocyclitols are selectively acylated at the 3'-N-position with 1-Z-imidazole, wherein Z is an amino protecting group; to produce novel 1-N-unprotected-poly-N-protected-4,6-di-O-(aminoglycosyl)-1,3-diaminocycli tols.

Selective 3'-N-acylation of

This invention relates to derivatives of polyene macrolide antibiotics containing an amino sugar moiety, the process for their preparation and pharmaceutical compositions containing them useful in the treatment of fungal infections.

Derivatives of polyene macrolide antibiotics containing an amino sugar

Novel 6'-amino derivatives of 4-0-aminoglycosyl-6-0-garosaminyl-1,3-diaminocyclitols, useful as antibacterial agents, are described.

6'-Amino derivatives of

The preparation of novel 2'-unsubstituted derivatives of 4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols, useful as antibacterial agents, is described.

2-Unsubstituted derivatives of

1,2'-di-N-4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols and 1,6'-di-N-alkyl-4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols and their acid addition salts are valuable as antibacterial agents. Also disclosed are 2'-N-alkyl-4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitol antibacterial agents which are also useful as intermediates in the preparation of the 1,2'-di-N-alkyl-4,6-di-O-(aminoglycosyl)-1,3-diaminocyclitols. Preferred compounds of this invention include 1,2'-di-N-ethylsisomicin and 1,6'-di-N-ethylsisomicin.

Di-N-alkylaminoglycosides, methods for their manufacture and novel

A novel process for preparing novel 1-N-acyl-4,6-di-(aminoglycosyl)aminocyclitols is disclosed. The compounds are useful as antibacterial agents.

Selective acylation of the C-1 amino group of aminoglycoside antibiotics

1-N-Alkyl-4,6-di-(aminoglycosyl)-1,3-diaminocyclitols, valuable as antibacterial agents, are prepared by treating an acid addition salt of a 4,6-di-(aminoglycosyl)-1,3-diamonocyclitol antibacterial agent in an inert solvent, preferably a protic solvent containing water, with one equivalent of a hydride donor reducing agent and with at least one equivalent of an aldehyde. The 1-N-alkyl-4,6-di-(aminoglycosyl)-1,3-diaminocyclitols are also prepared by treating the corresponding 1-N-acyl-4,6-di-(aminoglycosyl)-1,3-diaminocyclitol with an amide-reducing hydride reagent in an inert organic solvent. Other methods of preparing 1-N-alkyl-4,6-di-(aminoglycosyl)-1,3-diaminocyclitols include carrying out the foregoing processes with partially N-protected intermediates. Another useful process involves preparing a Schiff base of the 1-amino function of a partially N-protected 4,6-di-(aminoglycosyl)-1,3-diaminocyclitol followed by reduction of said Schiff base and removal of the N-protecting groups. Pharmaceutical compositions comprising 1-N-alkyl-4,6-di-(aminoglycosyl)-1,3-diaminocyclitols are described as well as the method of using said compositions to elicit an antibacterial response in a warm blooded animal having a susceptible bacterial infection.

1-N-alkyl-4,6-di-(aminoglycosyl)-1,3-diaminocyclitols, methods for their

1-N-Alkyl-Aminoglycoside-XK-88 derivatives, valuable as antibacterial agents, are prepared by the reaction of an acid addition salt of the corresponding 1-N-unsubstituted-Aminoglycoside-XK-88 antibacterial derivative or of a 2'-N-alkanoyl-Aminoglycoside-XK-88-5 derivative in an inert solvent, preferably a protic solvent containing water, with one equivalent of a hydride-donor reducing agent and with at least one equivalent of an aldehyde. The 2'-N-alkanoyl-Aminoglycoside-XK-88-5 intermediates are prepared by the reaction of a partially neutralized acid addition salt of Aminoglycoside-XK-88-5 with an acylating agent, and isolating the 2'-N-alkanoyl-Aminoglycoside-XK-88-5.

Growing community of inventors

Cedar Grove, NJ, United States of America

John J Wright