- 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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Paragraph 0011; 0016
(2018/04/01)
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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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Paragraph 0010; 0011; 0016
(2018/04/01)
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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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Paragraph 0218; 0231; 0232; 0233
(2017/04/11)
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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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Paragraph 0311; 0316
(2015/12/31)
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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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Paragraph 00165
(2015/08/06)
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- Flexible and modular syntheses of enantiopure 5-cis-substituted prolinamines from l-pyroglutamic acid
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A wide range (25 examples) of 5-cis-substituted prolinamines is prepared in five to ten steps starting from cheap l-pyroglutamic acid. Three routes, differing mainly in the order of introduction of the substituents at the 5-cis position, the pyrrolidine nitrogen atom, and the exocyclic amino function, are successfully developed.
- Prause, Felix,Kaldun, Johannes,Arensmeyer, Benjamin,Wennemann, Benedikt,Fr?hlich, Benjamin,Scharnagel, Dagmar,Breuning, Matthias
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p. 575 - 586
(2015/02/19)
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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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Paragraph 0252
(2014/07/08)
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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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Paragraph 0426
(2013/05/21)
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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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Page/Page column 131; 133
(2013/06/05)
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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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Paragraph 0348
(2013/12/03)
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- Synthesis and evaluation of novel orally active p53-MDM2 interaction inhibitors
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We have discovered and reported potent p53-MDM2 interaction inhibitors possessing dihydroimidazothiazole scaffold. Our lead showed strong activity in vitro, but did not exhibit antitumor efficacy in vivo for the low metabolic stability. In order to obtain orally active compounds, we executed further optimization of our lead by the improvement of physicochemical properties. Thus we furnished optimal compounds by introducing an alkyl group onto the pyrrolidine at the C-2 substituent to prevent the metabolism; and modifying the terminal substituent of the proline motif improved solubility. These optimal compounds exhibited good PK profiles and significant antitumor efficacy with oral administration on a xenograft model using MV4-11 cells having wild type p53.
- Miyazaki, Masaki,Naito, Hiroyuki,Sugimoto, Yuuichi,Yoshida, Keisuke,Kawato, Haruko,Okayama, Tooru,Shimizu, Hironari,Miyazaki, Masaya,Kitagawa, Mayumi,Seki, Takahiko,Fukutake, Setsuko,Shiose, Yoshinobu,Aonuma, Masashi,Soga, Tsunehiko
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p. 4319 - 4331
(2013/07/27)
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- NOVEL HEPATITIS C VIRUS INHIBITORS
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The invention provides compounds of formula (I): wherein Rings A and A' are independently 5-membered optionally substituted aromatic heterocycles; Q is C(=O)NR1R1' or formula U is C(R4)2, O, S, S(=O)2, C(R4)2C(R4)2, CH2O, OCH2, CH2S, SCH2, CH2S(=O)2, S(=O)CH2 or C=C(Ru )2; X is CH2, CHR12, CR12R12, O, S, S(=O)2 or NRx; m is 0, 1, 2 or 3; n is 0, 1, 2 or 3; the other variables are as defined in the claims, which are of use in the treatment or prophylaxis of hepatitis C virus infection, and related aspects.
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- HEPATITIS C VIRUS INHIBITORS
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This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds
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Page/Page column 115-116
(2012/04/10)
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- HEPATITIS C VIRUS INHIBITORS
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The present disclosure relates to compounds of formula I, compositions and methods for the treatment of hepatitis C virus (HCV) infection. Also disclosed are pharmaceutical compositions containing such compounds and methods for using these compounds in th
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Page/Page column 42
(2012/08/28)
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- HEPATITIS C VIRUS INHIBITORS
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This disclosure concerns novel compounds of Formula (I) as defined in the specification and compositions comprising such novel compounds. These compounds are useful antiviral agents, especially in inhibiting the function of the NS5A protein encoded by Hepatitis C virus (HCV). Thus, the disclosure also concerns a method of treating HCV related diseases or conditions by use of these novel compounds or a composition comprising such novel compounds.
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Page/Page column 113-114
(2010/11/03)
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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 that 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, atherosclero
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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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- 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, atheroscler
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