Novartis Vaccines & Diagnostics, Gmbh

University of Washington

Novartis Ag

Eric Harwood

Keith Bruce Pfister

Allan S Wagman

Toni Beth Kline

Simon C Ng

Niels H Andersen

Asha Yabannavar

Shuguang Zhu

Alice L Erwin

Jason Bowman

Khisimuzi E Mdluli

Ribhi Shawar

David M Ryckman

Xiao Shang

Timothy D Machajewski

Carla C Heise

Joyce Chou

Augustus O Okhamafe

Marion Wiesmann

Peter E Haroldsen

Shaopei Cai

Rampurna Gullapalli

Alison Hannah

Gabriel Galvin

Emil Samara

Jayesh Vora

Niels H Anderson

David Ryckman

Gabriel Calvin

Marc S Tesconi

The present invention relates to non-hydrate crystalline forms of 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one lactic acid salts, solid pharmaceutical formulations containing the same and methods of use. The present invention also relates to crystalline hydrates of 4-amino-5-fluoro-3-[6-(4-methylpiperazin-l-yl)-lH-benzimidazol-2-yl]-lH-quinolin-2-one lactic acid salts, pharmaceutical formulations containing the same and methods of use related thereto. The present invention further relates to crystalline solvates of 4-amino-5-fluoro-3-[6-(4-methylpiperazin-l-yl)-lH-benzimidazol-2-yl]-lH-quinolin-2-one lactic acid salts.

Crystalline and other forms of 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one lactic acid salts

A method for synthesizing a heterocyclic compound includes: reacting 1-methylpiperazine with 5-chloro-2-nitroaniline at an internal temperature sufficient to provide a compound of Formula VIH The 1-methylpiperazine and the 5-chloro-2-nitroaniline are reacted in a solvent that comprises water in an amount greater than 50 percent by volume based on the amount of the solvent and/or are reacted in a solvent that comprises an organic solvent component that has a boiling point of greater than 100&#xb0; C. at atmospheric pressure. 

Methods for synthesizing heterocyclic compounds

Antibacterial compounds of formula I are provided:  As well as stereoisomers, pharmaceutically acceptable salts, esters, and prodrugs thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of the compounds.

Antibacterial agents

Methods of treating cancer using 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one are provided. In particular, the methods are effective for the treatment of solid tumors or leukemias, including prostate, colorectal, breast, multiple myeloma, pancreatic, small cell carcinoma, acute myelogenous leukemia, chronic myelogenous leukemia, or myelo-proliferative disease. Further provided are methods of measuring the amount of 4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]quinolin-2(1H)-one and determining a metabolic profile therefore.

Methods of treating cancer and related methods

Methods of inhibiting fibroblast growth factor receptor 3 and treating various conditions mediated by fibroblast growth factor receptor 3 are provided that include administering to a subject a compound of Structure I, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I have the following structure where and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting fibroblast growth factor receptor 3 and for use in treating conditions mediated by fibroblast growth factor receptor 3 such as multiple myeloma. 

Inhibition of FGFR3 and treatment of multiple myeloma

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Seattle, WA, United States of America

Eric Harwood