160801-73-0

Upstream product

• 6638-79-5 N,O-dimethylhydroxylamine*hydrochloride 
• 53308-95-5 N-tert-butoxycarbonyl-L-norvaline 

Downstream Products

• 1034154-46-5 (S)-tert-butyl 1-oxo-1-phenylpentan-2-ylcarbamate 
• 856707-38-5 acetic acid (2S)-2-tert-butoxycarbonylamino-1-cyclopropylcarbamoylpentyl ester 
• 850252-34-5 (3S)-3-amino-N-cyclopropyl-2-hydroxyhexanamide hydrochloride 
• 160801-88-7 Boc-Phe-Leu-Nva-CONH-CH₂CH₃ 
• 160868-27-9 Boc-D-Phe-Leu-Nva-CONH-CH₂CH₃ 
• 209398-26-5 (3S)-3-(tert-butoxycarbonylamino)-2-hydroxyhexanoic acid 
• 402959-32-4 (S)-3-Amino-2-hydroxy-hexanoic acid 
• 160801-74-1 (2S)-2-(1,1-dimethylethoxycarbonylamino)pentanal 

Relevant academic research and scientific papers

Defining the Determinants of Specificity of Plasmodium Proteasome Inhibitors

The Plasmodium proteasome is an emerging antimalarial target due to its essential role in all the major life cycle stages of the parasite and its contribution to the establishment of resistance to artemisinin (ART)-based therapies. However, because of a similarly essential role for the host proteasome, the key property of any antiproteasome therapeutic is selectivity. Several parasite-specific proteasome inhibitors have recently been reported, however, their selectivity must be improved to enable clinical development. Here we describe screening of diverse libraries of non-natural synthetic fluorogenic substrates to identify determinants at multiple positions on the substrate that produce enhanced selectivity. We find that selection of an optimal electrophilic "warhead" is essential to enable high selectivity that is driven by the peptide binding elements on the inhibitor. We also find that host cell toxicity is dictated by the extent of coinhibition of the human β2 and β5 subunits. Using this information, we identify compounds with over 3 orders of magnitude selectivity for the parasite enzyme. Optimization of the pharmacological properties resulted in molecules that retained high potency and selectivity, were soluble, sufficiently metabolically stable and orally bioavailable. These molecules are highly synergistic with ART and can clear parasites in a mouse model of infection, making them promising leads as antimalarial drugs.

COMPOUNDS THAT INHIBIT PROTEASE CATHEPSIN S AND HCV REPLICATION

The present invention is directed to compounds that have the dual property of acting as cathepsin S inhibitors and of inhibiting HCV replication. Such compounds are therefore useful in treating disease states that include hepatitis C, Alzheimer's disease,

INDAZOLYL ESTER AND AMIDE DERIVATIVES FOR THE TREATMENT OF GLUCOCORTICOID RECEPTOR MEDIATED DISORDERS

Compounds of formula (I): The present invention relates to novel indazolyl ester or amide derivatives, to pharmaceutical compositions comprising such derivatives, to processes for preparing such novel derivatives and to the use of such derivatives as medicaments

HCV INHIBITORS

The present invention is directed to compounds that are antiviral agents. Specifically, the compounds of the present invention inhibit replication of HCV and are therefore useful in treating hepatitis C infections. The present invention is also directed to pharmaceutical compositions comprising these compounds and processes for preparing them.

HCV INHIBITORS

The present invention is directed to compounds that are antiviral agents. Specifically the compounds of the present invention inhibit replication of HCV and are therefore useful in treating hepatitis C infections. The present invention is also directed to pharmaceutical compositions comprising these compounds and processes for preparing them.

Pharmaceutical formulations and methods of treatment using the same

Pharmaceutical formulations containing at least one compound of Formulae I-XXVI herein and at least one surfactant. Pharmaceutically acceptable carriers and excipients may also be included in the formulations. The formulations of the present invention are suited for use in single unit dosages.

Liver/plasma concentration ratio for dosing hepatitis C virus protease inhibitor

Compositions and therapeutic combinations are provided including at least one compound selected from the group consisting of compounds of Formulae I to XXVI as defined herein as well as methods of treatment, prevention or amelioration of one or more symptoms of hepatitis C, treating disorders associated with HCV virus, modulating activity of HCV protease, in which liver to plasma concentration ratio of the compound ranges from about 2:1 to about 10:1.

Administration of HCV protease inhibitors in combination with food to improve bioavailability

Methods of treating, preventing or ameliorating one or more symptoms of hepatitis C in a subject comprising the step of administering at least one HCV protease inhibitor in combination with food are provided. Also provided are methods of increasing bioavailability of an HCV protease inhibitor and methods of increasing serum levels of an HCV protease inhibitor in a subject. All methods comprise adminstering at least one HCV protease inhibitor in combination with food, the at least one HCV protease inhibitor selected from the group consisting of compounds of Formulae I-XXVI, described herein. Administration of compounds of the present invention in combination with food provides improved bioavailability and increased peak serum levels of the compounds as compared to administration without food.

Keto-1,3,4-oxadiazoles as cathepsin K inhibitors

We have prepared a series of cathepsin K inhibitors bearing the keto-1,3,4-oxadiazole warhead capable of forming a hemithioketal complex with the target enzyme. By modifying binding moieties at the P1, P2, and prime side positions of the inhibitors, we have achieved selectivity over cathepsins B, L, and S, and have achieved sub-nanomolar potency against cathepsin K. This series thus represents a promising chemotype that could be used in diseases implicated by imbalances in cathepsin K activity such as osteoporosis.

Methods of treating hepatitis C virus

Methods for preventing, ameliorating or treating one or more symptoms of Hepatitis C virus (HCV), modulating HCV protease activity and/or inhibiting cathepsin activity in a subject, wherein the methods comprise administering to a subject in need of such treatment a dosage formulation containing at least one compound of Formulae I-XXVI herein, wherein the dosage formulation is capable of maintaining an average Cmin plasma concentration of the compound at or above 10 ng/ml.