C07D309/28

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOBLOGIN
20190010121 · 2019-01-10 ·

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

Enhanced anti-influenza agents conjugated with anti-inflammatory activity

Novel dual-targeted, bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents are disclosed. Exemplary drugs according to the invention include caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1), ZA-7-CA-amide (7) and ZA-7-Nap (43) for simultaneous inhibition of influenza virus neuraminidase and suppression of proinflammatory cytokines. Synthetic methods for preparation of these enhanced anti-influenza conjugate drugs are provided. The synthetic bifunctional ZA conjugates act synergistically towards protection of mice lethally infected by H1N1 or H5N1 influenza viruses. The efficacy of ZA-7-CA, ZA-7-CA-amide and ZA-7-Nap conjugates is much greater than the combination therapy of ZA with anti-inflammatory agents.

Enhanced anti-influenza agents conjugated with anti-inflammatory activity

Novel dual-targeted, bifunctional anti-influenza drugs formed by conjugation with anti-inflammatory agents are disclosed. Exemplary drugs according to the invention include caffeic acid (CA)-bearing zanamivir (ZA) conjugates ZA-7-CA (1), ZA-7-CA-amide (7) and ZA-7-Nap (43) for simultaneous inhibition of influenza virus neuraminidase and suppression of proinflammatory cytokines. Synthetic methods for preparation of these enhanced anti-influenza conjugate drugs are provided. The synthetic bifunctional ZA conjugates act synergistically towards protection of mice lethally infected by H1N1 or H5N1 influenza viruses. The efficacy of ZA-7-CA, ZA-7-CA-amide and ZA-7-Nap conjugates is much greater than the combination therapy of ZA with anti-inflammatory agents.

COMPOUNDS FOR MEDICINAL APPLICATIONS

The present invention provides compounds for use in treating and/or preventing influenza. The compound comprises a first and second domain in which the first domain comprises at least one anchoring group which binds to the surface of influenza viruses and the second domain comprises at least one anionic group. The first and second domains are covalently linked. Also provided are pharmaceutically acceptable salts, solvates, prodrugs or stereoisomer of the compounds.

STEREOSPECIFIC PROCESS FOR 3-HETEROCYCLYLCYCLOALIPHATIC-1,2-DIOLS
20180230112 · 2018-08-16 ·

A process for the stereoselective synthesis of chiral 3-heterocyclyl-1,2-dihydroxy cyclohexanes is disclosed. The process involves reacting a tricyclic nitrogenous heterocycle with an allyl carbonate in the presence of a chiral palladium catalyst followed by oxidation of the olefinic bond to provide 3-heterocyclyl-1,2-dihydroxy cyclohexanes, cyclopentanes and corresponding alicyclic heterocycles. Also disclosed are methods for converting the heterocyclyl-1,2-dihydroxy cyclohexanes to 2-amino-6-(heteroaryl)cyclohexanols (and related cyclic compounds).

STEREOSPECIFIC PROCESS FOR 3-HETEROCYCLYLCYCLOALIPHATIC-1,2-DIOLS
20180230112 · 2018-08-16 ·

A process for the stereoselective synthesis of chiral 3-heterocyclyl-1,2-dihydroxy cyclohexanes is disclosed. The process involves reacting a tricyclic nitrogenous heterocycle with an allyl carbonate in the presence of a chiral palladium catalyst followed by oxidation of the olefinic bond to provide 3-heterocyclyl-1,2-dihydroxy cyclohexanes, cyclopentanes and corresponding alicyclic heterocycles. Also disclosed are methods for converting the heterocyclyl-1,2-dihydroxy cyclohexanes to 2-amino-6-(heteroaryl)cyclohexanols (and related cyclic compounds).

CYCLOALKENYL HYDROXAMIC ACID DERIVATIVES AND THEIR USE AS HISTONE DEACETYLASE INHIBITORS

The present invention provides compounds of formula (I):

##STR00001##

or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein W, X, n, s, t, and R.sup.a are as described herein. The present invention relates generally to selective inhibitors of histone deacetylase and to methods of making and using them.

CYCLOALKENYL HYDROXAMIC ACID DERIVATIVES AND THEIR USE AS HISTONE DEACETYLASE INHIBITORS

The present invention provides compounds of formula (I):

##STR00001##

or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein W, X, n, s, t, and R.sup.a are as described herein. The present invention relates generally to selective inhibitors of histone deacetylase and to methods of making and using them.

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN
20180201577 · 2018-07-19 ·

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.

COMPOUNDS AND USES THEREOF FOR THE MODULATION OF HEMOGLOBIN
20180201577 · 2018-07-19 ·

Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.