- Compound used for inhibiting hepatitis C virus, and pharmaceutical applications thereof
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The invention relates to a compound which is represented by formula I, is used for inhibiting hepatitis C virus, and possesses excellent bioavailability, and a nontoxic pharmaceutically acceptable salt thereof. The compound possesses extremely high inhibition effect on HCV of all genotypes. In the formula I, R is used for representing hydrogen atom, glycyl, L-alanyl, L-leucyl, L-valyl, or L-isoleucyl.
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- Deuterated antiviral active compounds for hepatitis C viruses
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The invention relates to antiviral compounds for hepatitis C viruses (HCVs) and nontoxic pharmacologically-acceptable salts thereof, wherein the compounds are represented by a formula I shown in the description and have good bioavailability, and the compounds have potent inhibiting effects on the all-genotypic HCVs. In the structural formula I, R1, R2, R3 and R4 are independently selected from methyl (-CH3) or deuterated methyl (-CD3); X1, X2, X3, X4 and X5 are separately hydrogen (H) or deuterium (D); and one of the R1, the R2, the R3 and the R4 must be deuterated methyl (-CD3) or one of theX1, the X2, the X3, the X4, and the X5 must be deuterium (D).
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- BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided herein is a bridged bring compound of formula (I) or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating treat hepatitis C virus (HCV) infection or hepatitis C disease. Furthermore provided herein are pharmaceutical compositions containing the compounds and the method of using the compounds or pharmaceutical compositions thereof in the treatment of HCV infection or hepatitis C.
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- BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
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Provided herein is a bridged bring compound of formula (I) or a stereoisomer, a tautomer, an N-oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof, which can be used for treating treat hepatitis C virus (HCV) infection or hepatitis C disease. Furthermore provided herein are pharmaceutical compositions containing the compounds and the method of using the compounds or harmaceutical com ositions thereof in the treatment of HCV infection or he atitis C.
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- PROCESSES FOR PREPARING ANTIVIRAL COMPOUNDS
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The present disclosure provides processes for the preparation of a compound of formula: which is useful as an antiviral agent. The disclosure also provides compounds that are synthetic intermediates.
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- ANTIVIRAL COMPOUNDS
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The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.
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- ANTIVIRAL COMPOUNDS
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The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.
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- HEPATITIS C VIRUS INHIBITORS
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The invention provides compounds of formula (I): wherein the variables are defined in the specification, or a pharmaceutically-acceptable salt thereof, that are inhibitors of replication of the hepatitis C virus. The invention also provides pharmaceutical compositions comprising such compounds, methods of using such compounds to treat hepatitis C viral infections, and processes and intermediates useful for preparing such compounds.
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- CONDENSED IMIDAZOLYLIMIDAZOLES AS ANTIVIRAL COMPOUNDS
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The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.
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- ANTIVIRAL COMPOUNDS
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The disclosure is related to anti-viral compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.
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- N-ACYL CYCLIC AMINE DERIVATIVE OR PHARMACEUTICALLY ACCEPTABLE SALT THEREOF
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The present invention provides compounds which show high effectiveness against positive symptoms, negative symptoms and cognitive dysfunction in schizophrenia and reduce conventional side-effect risks as well as have remarkable effects for central neurolo
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- Discovery, structure - Activity relationship, and pharmacological evaluation of (5-substituted-pyrrolidinyl-2-carbonyl)-2-cyanopyrrolidines as potent dipeptidyl peptidase IV inhibitors
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A series of (5-substituted pyrrolidinyl-2-carbonyl)-2-cyanopyrrolidine (C5-Pro-Pro) analogues was discovered as dipeptidyl peptidase IV (DPPIV) inhibitors as a potential treatment of diabetes and obesity. X-ray crystallography data show that these inhibitors bind to the catalytic site of DPPIV with the cyano group forming a covalent bond with the serine residue of DPPIV. The C5-substituents make various interactions with the enzyme and affect potency, chemical stability, selectivity, and PK properties of the inhibitors. Optimized analogues are extremely potent with subnanomolar Ki's, are chemically stable, show very little potency decrease in the presence of plasma, and exhibit more than 1,000-fold selectivity against related peptidases. The best compounds also possess good PK and are efficacious in lowering blood glucose in an oral glucose tolerance test in ZDF rats.
- Pei, Zhonghua,Li, Xiaofeng,Longenecker, Kenton,Von Geldern, Thomas W.,Wiedeman, Paul E.,Lubben, Thomas H.,Zinker, Bradley A.,Stewart, Kent,Ballaron, Stephen J.,Stashko, Michael A.,Mika, Amanda K.,Beno, David W. A.,Long, Michelle,Wells, Heidi,Kempf-Grote, Anita J.,Madar, David J.,McDermott, Todd S.,Bhagavatula, Lakshmi,Fickes, Michael G.,Pireh, Daisy,Solomon, Larry R.,Lake, Marc R.,Edalji, Rohinton,Fry, Elizabeth H.,Sham, Hing L.,Trevillyan, James M.
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p. 3520 - 3535
(2007/10/03)
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- Discovery of 2-[4-{{2-(2S,5R)-2-cyano-5-ethynyl-1-pyrrolidinyl]-2-oxoethyl] amino-4-methyl-1-piperidinyl]-4-pyridinecarboxylic acid (ABT-279): A very potent, selective, effective, and well-tolerated inhibitor of dipeptidyl peptidase-IV, useful for the treatment of diabetes
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Dipeptidyl peptidase-IV (DPP-IV) inhibitors are poised to be the next major drug class for the treatment of type 2 diabetes. Structure-activity studies of substitutions at the C5 position of the 2-cyanopyrrolidide warhead led to the discovery of potent inhibitors of DPP-IV that lack activity against DPP8 and DPP9. Further modification led to an extremely potent (KiDPP-IV = 1.0 nM) and selective (KiDPP8 > 30 μM; KiDPP9 > 30 μM) clinical candidate, ABT-279, that is orally available, efficacious, and remarkably safe in preclinical safety studies.
- Madar, David J.,Kopecka, Hana,Pireh, Daisy,Yong, Hong,Pei, Zhonghua,Li, Xiaofeng,Wiedeman, Paul E.,Djuric, Stevan W.,Von Geldern, Thomas W.,Fickes, Michael G.,Bhagavatula, Lakshmi,McDermott, Todd,Wittenberger, Steven,Richards, Steven J.,Longenecker, Kenton L.,Stewart, Kent D.,Lubben, Thomas H.,Ballaron, Stephen J.,Stashko, Michael A.,Long, Michelle A.,Wells, Heidi,Zinker, Bradley A.,Mika, Amanda K.,Beno, David W. A.,Kempf-Grote, Anita J.,Polakowski, James,Segreti, Jason,Reinhart, Glenn A.,Fryer, Ryan M.,Sham, Hing L.,Trevillyan, James M.
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p. 6416 - 6420
(2008/04/18)
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- PHARMACEUTICAL COMPOSITIONS AS INHIBITORS OF DIPEPTIDYL PEPTIDASE-IV (DPP-IV)
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The present invention relates to compounds which inhibit dipeptidyl peptidase IV (DPP-IV) and are useful for the prevention or treatment of diabetes, especially type II diabetes, as well as hyperglycemia, Syndrome X, hyperinsulinemia, obesity, atherosclerosis, and various immunomodulatory diseases.
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- COMPOUNDS HAVING PROLYL OLIGOPEPTIDASE INHIBITORY ACTIVITY
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The invention provides a compound of formula (I), wherein in the formula X, R1, R2 and R3 are as defined in claim 1, or a pharmaceutically acceptable salt or ester thereof, useful as a prolyl oligopeptidase inhibitor. The compounds of formula (I) can be used for the treatment of diseases or conditions where prolyl oligopeptidase inhibitors are indicated to be effective, for example for the treatment of neurodegenerative diseases, such as Alzheimer's disease and senile dementia
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