223 results about "HIV Protease Inhibitor" patented technology

This invention relates to a novel class of peptides having the Formula (I):

which are useful as serine protease inhibitors, and more particularly as Hepatitis C virus(HCV) NS3 protease inhibitors. This invention also relates to pharmaceutical compositions comprising these compounds and methods of using the same in the treatment of HCV infection.

An anti-HIV agent containing, as an active ingredient, a 4-oxoquinoline compound represented by the following formula [I]

wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof. The compound of the present invention has HIV integrase inhibitory action and is useful as an anti-HIV agent for the prophylaxis or therapy of AIDS. Moreover, by a combined use with other anti-HIV agents such as protease inhibitors, reverse transcriptase inhibitors and the like, the compound can become a more effective anti-HIV agent. Since the compound has high inhibitory activity specific for integrases, it can provide a safe pharmaceutical agent with a fewer side effects for human.

A process is provided for preparing the HIV protease inhibitor atazanavir bisulfate wherein a solution of atazanavir free base is reacted with concentrated sulfuric acid in an amount to react with less than about 15% by weight of the free base, seeds of Form A crystals of atazanavir bisulfate are added to the reaction mixture, and as crystals of the bisulfate form, additional concentrated sulfuric acid is added in multiple stages at increasing rates according to a cubic equation, to effect formation of Form A crystals of atazanavir bisulfate. A process is also provided for preparing atazanavir bisulfate as Pattern C material. A novel form of atazanavir bisulfate is also provided which is Form E3 which is a highly crystalline triethanolate solvate of the bisulfate salt from ethanol.

The present invention relates to compounds that are useful as protease inhibitors, particularly as serine protease inhibitors, and more particularly as hepatitis C NS3 protease inhibitors. As such, they act by interfering with the life cycle of the hepatitis C virus and are also useful as antiviral agents. This invention also relates to pharmaceutical compositions comprising these compounds. The compounds and pharmaceutical compositions of this invention are particularly well suited for inhibiting HCV NS3 protease activity and consequently, may be advantageously used as therapeutic agents against the hepatitis C virus and other viruses that are dependent upon a serine protease for proliferation. This invention also relates to methods for inhibiting the activity of proteases, including hepatitis C virus NS3 protease and other serine proteases, using the compounds of this invention and related compounds.

The present invention discloses compounds of formula I, II and III or pharmaceutically acceptable salts, esters, or prodrugs thereof:

which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

Bacteria which co-express protease inhibitors and protease sensitive therapeutic agents, which are surface displayed, secreted and/or released and result in their localized production and maintenance within a target tissue and inactivation outside of the target tissue, thereby increasing therapeutic activity and reducing the systemic toxicity. The bacteria may be attenuated, non-pathogenic, low pathogenic or a probiotic. Protease sensitivity may be further accomplished by engineering protease degradation sites within the therapeutic agents, further enhancing the inactivation outside of the target tissue while retaining activity within the target tissue through co-expression of a protease inhibitor. Novel chimeric proteins secreted by bacteria, including chimeric toxins targeted to neoplastic cells, tumor matrix cells and cells of the immune system, and combination therapies of these protease inhibitor:chimeric toxin-expressing bacteria together with small-molecule and biologic agents are also described. Non-conjugative bacteria limiting exchange of genetic material, and antibody resistant bacteria are also provided.

The present invention provides methods for identifying compounds useful as HCV protease inhibitors.

The present invention relates to compounds of Formula I, or a pharmaceutically acceptable salt, ester, or prodrug, thereof:

which inhibit serine protease activity, particularly the activity of hepatitis C virus (HCV) NS3-NS4A protease. Consequently, the compounds of the present invention interfere with the life cycle of the hepatitis C virus and are also useful as antiviral agents. The present invention further relates to pharmaceutical compositions comprising the aforementioned compounds for administration to a subject suffering from HCV infection. The invention also relates to methods of treating an HCV infection in a subject by administering a pharmaceutical composition comprising the compounds of the present invention.

The invention relates to a combination of treatments, more particularly a combination treatment for HIV-1 infection. The present invention is directed to the use of bryostatin-1 and their natural and synthetic derivatives for AIDS therapy, in particular to the use of bryostatins in combination with other active drugs such as Histone Deacetylases (HDACs) inhibitors and anti-retrovirals, for the treatment of HIV-1 latency. According to the present invention, we provide a combination therapy for the treatment of HIV-1 latency which employs bryostatin-1 (and analogues) and one of the following HDAC inhibitors; valproic acid, butyrate derivatives, hydroxamic acids and benzamides. While HDACi can be used in continuous dosing protocol, bryostatins can be used following a cyclical dosing protocol. Bryostatins can be formulated in pharmaceutical acceptable carriers including nanoparticles, phospholipids nanosomes and/or biodegradable polymer nanospheres. This combination therapy needs to be used in patients treated with antiretroviral therapy (HIV-1 protease inhibitors, HIV-1 reverse transcriptase inhibitors, HIV-1 integrase inhibitors, CCR5 co-receptor inhibitors and fusion inhibitors).

The present invention relates to a process for the stereoselective enzymatic reduction of 1-halo-2-oxo-3-(protected)amino-4-substituted-butanes utilizing certain species of Rhodococcus and Brevibacterium. The product 1-halo-2-hydroxy-3-(protected)amino-4-substituted-butanes, which are useful as intermediates in the synthesis of compounds that are inhibitors of ACE, renin and HIV proteases, are obtained in high yield and, particularly, in very high diastereomeric purity. The process is advantageously highly selective for the (3S,2R) enantiomer of the product.

The invention relates to methods of targeted drug delivery of antiviral compounds, including, chemical agents (like nucleoside analogs or protease inhibitors) and nucleic acid based drugs (like DNA vaccines, antisense oligonucleotides, ribozymes, catalytic DNA (DNAzymes) or RNA molecules, siRNAs or plasmids encoding thereof). Furthermore, the invention relates to targeted drug delivery of antiviral compounds to intracellular target sites within cells, tissues and organs, in particular to target sites within the central nervous system (CNS), into and across the blood-brain barrier, by targeting to internalizing uptake receptors present on these cells, tissues and organs. Thereto, the antiviral compounds, or the pharmaceutical acceptable carrier thereof, are conjugated to ligands that facilitate the specific binding to and internalization by these receptors.

The present disclosure concerns peptides and peptidomimetics having inhibitory activity against serine proteases. The disclosed peptides and peptidomimetics are particularly useful as selective inhibitors of matriptase and MTSP1. Pharmaceutical compositions comprising serine protease inhibitors and methods for administering the compositions also are disclosed.

The present invention encompasses methods and compositions for the treatment and prevention of chronic obstructive pulmonary disease (COPD) or emphysema, typically smoking-induced emphysema. More specifically, the present invention relates to the treatment and prevention of COPD or emphysema by inhalation of alpha one-antitrypsin (AAT).

The present invention relates to synthetic processes useful in the preparation of macrocyclic compounds of Formula (I) that are useful as inhibitors of the hepatitis C virus NS3 protease and have application in the treatment of conditions caused by the hepatitis C virus. The present invention also encompasses intermediates useful in the disclosed synthetic processes and the methods of their preparation.

Described are novel protease inhibitors and methods for using said protease inhibitors in the treatment of human immunodeficiency virus (HIV) infection.

HIV protease inhibitors are among the most powerful drugs in suppressing HIV in human patients. However, HIV developed resistance to all protease inhibitor drugs so far marketed or used in clinical trials. HIV generates resistance by mutating its protease. The strains of HIV containing mutant proteases less vulnerable to inhibitor drug are able to replicate better and maintain the infection. No effective principle exists for the design of resistance-proof HIV protease inhibitors (HIVPr). A new inhibitor has been developed based on a new concept for designing resistance invulnerable HIVPr inhibitors. In vitro data have shown that this inhibitor is effective against many known HIVPr mutants resistant to other HIVPr inhibitor drugs. The new concept is, therefore, generally applicable for the design of other resistance invulnerable HIVPr inhibitor drugs.

The present invention provides pharmaceutical formulations of an HCV protease inhibitor in a solid dispersion with an excipient which provided advantageous pharmacokinetic properties for inhibiting or treating HCV infection. In preferred embodiments, the excipient is at least one polymer. The present invention also provides processes for manufacturing such formulations as well as uses of said composition for the manufacture of a medicament for treating or ameliorating one or more symptoms of HCV or disorders associated with HCV in a subject in need thereof using said formulations.