- Discovery of novel tricyclic indole derived inhibitors of HCV NS5B RNA dependent RNA polymerase
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The characterization of HCV genome has identified various vital functional proteins involved in the life cycle of hepatitis C virus. This has resulted in many novel enzymatic targets that are potential for development of therapeutic agents. The HCV RNA de
- Venkatraman, Srikanth,Velazquez, Francisco,Gavalas, Stephen,Wu, Wanli,Chen, Kevin X.,Nair, Anilkumar G.,Bennett, Frank,Huang, Yuhua,Pinto, Patrick,Jiang, Yueheng,Selyutin, Oleg,Vibulbhan, Bancha,Zeng, Qingbei,Lesburg, Charles,Duca, Jose,Huang, Hsueh-Cheng,Agrawal, Sony,Jiang, Chuan-Kui,Ferrari, Eric,Li, Cheng,Kozlowski, Joseph,Rosenblum, Stuart,Shih, Neng-Yang,Njoroge, F. George
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p. 2007 - 2017
(2013/04/24)
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- Development of potent dipeptide-type SARS-CoV 3CL protease inhibitors with novel P3 scaffolds: Design, synthesis, biological evaluation, and docking studies
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We report the design and synthesis of a series of dipeptide-type inhibitors with novel P3 scaffolds that display potent inhibitory activity against SARS-CoV 3CLpro. A docking study involving binding between the dipeptidic lead compound 4 and 3CLpro suggested the modification of a structurally flexible P3 N-(3-methoxyphenyl)glycine with various rigid P3 moieties in 4. The modifications led to the identification of several potent derivatives, including 5c-k and 5n with the inhibitory activities (Ki or IC50) in the submicromolar to nanomolar range. Compound 5h, in particular, displayed the most potent inhibitory activity, with a Ki value of 0.006 μM. This potency was 65-fold higher than the potency of the lead compound 4 (Ki = 0.39 μM). In addition, the Ki value of 5h was in very good agreement with the binding affinity (16 nM) observed in isothermal titration calorimetry (ITC). A SAR study around the P3 group in the lead 4 led to the identification of a rigid indole-2-carbonyl unit as one of the best P3 moieties (5c). Further optimization showed that a methoxy substitution at the 4-position on the indole unit was highly favorable for enhancing the inhibitory potency.
- Thanigaimalai, Pillaiyar,Konno, Sho,Yamamoto, Takehito,Koiwai, Yuji,Taguchi, Akihiro,Takayama, Kentaro,Yakushiji, Fumika,Akaji, Kenichi,Chen, Shen-En,Naser-Tavakolian, Aurash,Sch?n, Arne,Freire, Ernesto,Hayashi, Yoshio
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p. 372 - 384
(2013/10/01)
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- TRICYCLIC INDOLE DERIVATIVES AND METHODS OF USE THEREOF
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The present invention relates to Tricyclic Indole Derivatives, compositions comprising at least one Tricyclic Indole Derivatives, and methods of using the Tricyclic Indole Derivatives for treating or preventing a viral infection or a virus-related disorder in a patient
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Page/Page column 51; 52
(2010/01/07)
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- 4,5-RING ANNULATED INDOLE DERIVATIVES FOR TREATING OR PREVENTING OF HCV AND RELATED VIRAL INFECTIONS
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The present invention relates to 4,5-ring annulated indole derivatives, compositions comprising at least one 4,5-ring annulated indole derivatives, and methods of using the 4,5-ring annulated indole derivatives for treating or preventing a viral infection or a virus-related disorder in a patient. Wherein ring Z, of formula (I), is a cyclopentyl, cyclopentenyl, 5-membered heterocycloalkyl, 5-membered heterocycloalkenyl or 5-membered heteroaryl ring.
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Page/Page column 135; 139
(2008/12/07)
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- CHEMOKINE RECEPTOR ANTAGONISTS
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A compound of formula (I) or a pharmaceutically acceptable salt or prodrug ester thereof, wherein the variants R, R9, Z, X, Q and Y are defined in the specification.
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Page/Page column 60
(2010/02/13)
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- ANTI-INFLAMMATORY INDOLE DERIVATIVES
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Compounds of formula (I) or a pharmaceutically acceptable salt, in vivo hydrolysable ester, or an N-C1-6alkyl or N,N-di-(C1-6alkyl)amide thereof, where X is CH2 or SO2; R1 is an aryl optionally substituted by alkyl, alkenyl, alkynyl, halo, haloalkyl inclu
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- Monocyte chemoattractant protein-1 inhibitor compounds
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The invention concerns the use of a compound of the formula (I) in which Z, X, T, A, R1, R2, p and q have any of the meanings defined herein, and their pharmaceutically acceptable salts or in vivo hydrolysable esters, in the treatment of a disease or condition mediated by monocyte chemoattractant protein-1 (MCP-1). Certain of the components of formula (I) are novel and are provided, together with pharmaceutical compositions thereof, as further features of the invention.
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- Indole derivatives as MCP-1 receptor antagonists
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The invention concerns pharmaceutically useful indoles of formula (I), in which Z, X, T, A, R1, R2, p and q have any of the meanings defined herein, and their pharmaceutically acceptable salts or in vivo hydrolysable esters, as well
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