Salts and Polymorph Screens for Bedaquiline.

Bedaquiline is used to treat multi-resistant tuberculosis in adults. The fumarate salt is commercially available and used in the product Sirturo. To provide open access to bedaquiline molecule once the patent on the chemical substance expires, new salts were screened.

Maleate salts of bedaquiline.

Bedaquiline is one of two important new drugs for the treatment of drug-resistant tuberculosis (TB). It is marketed in the US as its fumarate salt, but only a few salts of bedaquiline have been structurally described so far. We present here five crystal structures of bedaquilinium maleate {systematic name: [4-(6-bromo-2-meth-oxy-quinolin-3-yl)-3-hy-droxy-3-(naphthalen-1-yl)-4-phenyl-but-yl]di-methyl-aza-nium 3-carb-oxy-prop-2-enoate}, CHBrNO ·CHO , namely, a hemihydrate, a tetra-hydro-furan (THF) solvate, a mixed acetone/hexane solvate, an ethyl acetate solvate, and a solvate-free structure obtained from the acetone/hexane solvate by single-crystal-to-single-crystal desolvation.

Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]- 3-[2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]- 6,6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: a potential therapeutic agent for the treatment of hepatitis C infection.

Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-alpha or polyethylene glycol (PEG)-interferon-alpha alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response.