Merck Sharp + Dohme Corp.

Hoffmann-La Roche Inc.

Madrigal Pharmaceuticals, Inc.

Trius Therapeutics, Inc.

Vitae Pharmaceuticals, LLC (121374)

F. Hoffmann-La Roche Ag

Robert J Duguid

Charles Howard Reynolds

Jacqueline A Ware

Douglas W Phillipson

D Keith Hester, Ii

Katharina Reichenbacher

Ping Wang

Martha Jean Kelly

Rebecca Taub

Lianhe Shu

Duk Soon Choi

Gang Dong

Anna Chasnoff

Edwin L Crow

D Keith Hester

Charles H Reynolds

Martha Kelly

Carrie A Costello

Douglas Phillipson

John M Finn

John Anthony Grosso

Sergiy Krasutsky

Katharina Reichenbächer

Jaqueline A Ware

Keith D Hester

Jaqueline A Simson

The disclosure describes methods of synthesis of pyridazinone compounds as thyroid hormone analogs and their prodrugs. Preferred methods according to the disclosure allow for large-scale preparation of pyridazinone compounds having high purity. In some embodiments, preferred methods according to the disclosure also allow for the preparation of pyridazinone compounds in better yield than previously used methods for preparing such compounds. Also disclosed are morphic forms of a pyridazinone compound. Further disclosed is a method for treating resistance to thyroid hormone in a subject having at least one TR&#x3b2; mutation.

Methods of synthesizing thyroid hormone analogs and polymorphs thereof

The present disclosure relates to processes for the production of salts and crystalline forms of a compound having the formula. 

Inhibitors of ROR&#x3b3;

A crystalline form of crystalline (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate, methods of making the crystalline form and pharmaceutical compositions comprising the crystalline form are useful antibiotics. Further, the derivatives of the present invention may exert potent antibacterial activity versus various human and animal pathogens, including Gram-positive bacteria such as Staphylococi, Enterococci and Streptococi, anaerobic microorganisms such asand Clostridia, and acid-resistant microorganisms such asand. Accordingly, the compositions comprising the crystalline form may be used in antibiotics.

Forms of R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate

A crystalline form of crystalline (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate, methods of making the crystalline form and pharmaceutical compositions comprising the crystalline form are useful antibiotics. Further, the derivatives of the present invention may exert potent antibacterial activity versus various human and animal pathogens, including Gram-positive bacteria such asand, anaerobic microorganisms such asand, and acid-resistant microorganisms such asand. Accordingly, the compositions comprising the crystalline form may be used in antibiotics.

Methods of preparing a class of oxazolidinones useful to impede bacterial growth are disclosed.

Methods for preparing oxazolidinones and compositions containing them

Method of synthesizing thyroid hormone analogs and polymorphs thereof

Dosage forms or pharmaceutical compositions comprise a compound having the structure of Formula IV:  wherein n is a non-negative integer; wherein each Z is an oxazolidinone-containing moiety having antibiotic activity in vivo upon cleaving, wherein M is independently ORor NRR; wherein Rand Rare independently selected from the group consisting of H, an optionally-substituted hydrocarbyl residue or a pharmaceutically acceptable cation; wherein the compound in the dosage form or a pharmaceutical composition is present in an amount effective for treating or preventing an antibacterial infection in a mammalian subject. Methods of preparing and using these dosage forms or pharmaceutical compositions are also disclosed.

Oxazolidinone containing dimer compounds, compositions and methods to make and use

A crystalline form of crystalline (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate, methods of making the crystalline form and pharmaceutical compositions comprising the crystalline form are useful antibiotics. Further, the derivatives of the present invention may exert potent antibacterial activity versus various human and animal pathogens, including Gram-positive bacteria such as Staphylococi, Enterococci and Streptococi , anaerobic microorganisms such as Bacteroides and Clostridia, and acid-resistant microorganisms such as Mycobacterium tuberculosis and Mycobacterium avium. Accordingly, the compositions comprising the crystalline form may be used in antibiotics.

Crystalline form of R)-3-(4-(2-(2-methyltetrazol-5-yl)pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyl oxazolidin-2-one dihydrogen phosphate

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Glenmont, NY, United States of America

Robert J Duguid