189816-05-5Relevant articles and documents
Hepatitis C Virus Inhibitors
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Page/Page column 27-28, (2009/12/02)
Hepatitis C virus inhibitors having the general formula are disclosed. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
NOVEL MACROCYCLIC INHIBITORS OF HEPATITIS C VIRUS REPLICATION
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, (2009/10/31)
The embodiments provide compounds of the general Formulae I, II, III, IV, V, VI, VII, and X, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
Discovery of novel, potent and bioavailable proline-urea based macrocyclic HCV NS3/4A protease inhibitors
Vendeville, Sandrine,Nilsson, Magnus,Kock, Herman de,Lin, Tse-I,Antonov, Dmitry,Classon, Bjoern,Ayesa, Susana,Ivanov, Vladimir,Johansson, Per-Ola,Kahnberg, Pia,Eneroth, Anders,Wikstrom, Kristina,Vrang, Lotta,Edlund, Michael,Lindstroem, Stefan,Vreken, Wim Van de,McGowan, David,Tahri, Abdellah,Hu, Lili,Lenz, Oliver,Delouvroy, Frederic,Dooren, Marleen Van,Kindermans, Natalie,Surleraux, Dominique,Wigerinck, Piet,Rosenquist, Asa,Samuelsson, Bertil,Simmen, Kenneth,Raboisson, Pierre
scheme or table, p. 6189 - 6193 (2009/08/07)
A novel series of P3-truncated macrocyclic HCV NS3/4A protease inhibitors containing a P2 proline-urea or carbamate scaffold was synthesized. Very potent inhibitors were obtained through the optimization of the macrocycle size, urea and proline substitution, and bioisosteric replacement of the P1 carboxylic acid moiety. Variation of the lipophilicity by introduction of small lipophilic substituents resulted in improved PK profiles, ultimately leading to compound 13Bh, an extremely potent (Ki = 0.1 nM, EC50 = 4.5 nM) and selective (CC50 (Huh-7 cells) > 50 μM) inhibitor, displaying an excellent PK profile in rats characterized by an oral bioavailability of 54% and a high liver exposure after oral administration.
Hepatitis C virus inhibitors
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Page/Page column 33-34, (2008/06/13)
The present disclosure is generally directed to antiviral compounds, and more specifically directed to compounds which inhibit the function of the NS3 protease (also referred to herein as “serine protease”) encoded by Hepatitis C virus (HCV), compositions comprising such compounds, and methods for inhibiting the function of the NS3 protease.
Substituted cycloalkyl P1' hepatitis C virus inhibitors
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Page/Page column 20, (2010/02/06)
The present invention relates to tripeptide compounds, compositions and methods for the treatment of hepatitis C virus (HCV) infection. In particular, the present invention provides novel tripeptide analogs, pharmaceutical compositions containing such analogs and methods for using these analogs in the treatment of HCV infection.
Hepatitis C inhibitor peptides
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, (2008/06/13)
Disclosed herein are hepatitis C viral protease inhibitors of formula (I): wherein a is0or1; b is0or1; Y is H or C1-6alkyl; B is H, an acyl derivative or a sulfonyl derivative; R6, when present, is C1-6alkyl substituted wi
HETEROCYCLICSULFONAMIDE HEPATITIS C VIRUS INHIBITORS
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Page 47, (2010/02/05)
The present invention relates to tripeptide compounds, compositionscontaining such compounds and methods for using such compounds for the treatment of heptitis C virus (HCV) infection. In particular, the present invention provides novel tripeptide analogs, pharmaceutical compositionscontaining such analogs and methods for using these analogs in the treatment of HCV infection.
Enzymatic resolution of 1-amino-2-vinylcyclopropyl caboxylic acid methyl ester
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, (2008/06/13)
An enantiomeric-resolving process for obtaining (1R,2S)-1-amino-2-vinylcyclopropyl carboxylic acid methyl ester by use of an esterase, and especially Alcalase?, is disclosed.
Discovery of a novel class of selective non-peptide antagonists for the human neurokinin-3 receptor. 1. Identification of the 4-quinolinecarboxamide framework
Giardina, Giuseppe A. M.,Sarau, Henry M.,Farina, Carlo,Medhurst, Andrew D.,Grugni, Mario,Raveglia, Luca F.,Schmidt, Dulcie B.,Rigolio, Roberto,Luttmann, Mark,Vecchietti, Vittorio,Hay, Douglas W. P.
, p. 1794 - 1807 (2007/10/03)
A novel class of potent and selective non-peptide neurokinin-3 (NK-3) receptor antagonists, featuring the 4-quinolinecarboxamide framework, has been designed based upon chemically diverse NK-1 receptor antagonists. The novel compounds 33-76, prompted by chemical modifications of the prototype 4, have been characterized by binding analysis using a membrane preparation of chinese hamster ovary (CHO) cells expressing the human neurokinin-3 receptors (hNK-3-CHO), and clear structure-activity relationships (SARs) have been established. From SARs, (R)-N-[α-(methoxycarbonyl)benzyl]-2- phenylquinoline-4-carboxamide (65, SB 218795, hNK-3-CHO binding K(i) = 13 nM) emerged as one of the most potent compounds of this novel class. Selectivity studies versus the other neurokinin receptors (hNK-2-CHO and hNK-1-CHO) revealed that 65 is about 90-fold selective for hNK-3 versus hNK-2 receptors (hNK-2-CHO binding K(i) = 1221 nM) and over 7000-fold selective versus hNK-1 receptors (hNK-1-CHO binding K(i) = >100 μM). In vitro functional studies in rabbit isolated iris sphincter muscle preparation demonstrated that 65 is a competitive antagonist of the contractile response induced by the potent and selective NK-3 receptor agonist senktide with a K(b) = 43 nM. Overall, the data indicate that 65 is a potent and selective hNK-3 receptor antagonist and a useful lead for further chemical optimization.