- ANTIVIRAL COMPOUNDS CONTAINING NITRILE
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The invention relates to compounds of formula (I'') wherein R, R1,R2,R3,p, q and q' are as defined in the description, pharmaceutical compositions comprising the compounds, methods of treating a coronavirus infection, such
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Page/Page column 81; ; 265-267
(2021/12/30)
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- A diastereoselective synthesis of boceprevir's gem-dimethyl bicyclic [3.1.0] proline intermediate from an insecticide ingredient cis-cypermethric acid
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An efficient multi-gram synthesis of (1R,2S,5S)-methyl 6,6-dimethyl-3-azabicyclo[3.1.0]hexane-2-carboxylate, a key chiral bicyclic proline fragment employed in the construction of the potent anti-HCV drug boceprevir, has been presented. The synthetic route commences with the readily available cis-cypermethric acid, a cheap source of the cyclopropane ring required in the targeted compound, and utilizes the cis-orientation of the 2,2-dichlorovinyl and carboxylic acid side arms, already present in the starting material, to effect a diastereoselective construction of the proline moiety.
- Kallam, Srinivasa Reddy,Eda, Vishnuvardhan Reddy,Sen, Saikat,Datrika, Rajender,Rapolu, Rajesh Kumar,Khobare, Sandip,Gajare, Vikas,Banda, Malavika,Khan, Rashid Abdul Rehman,Singh, Manpreet,Lloyd, Michael,Kandagatla, Bhaskar,Janagili, Moses Babu,Tadikonda, Veerabhadra Pratap,Vidavalur, Siddaiah,Iqbal, Javed,Fox, Martin E.,Dahanukar, Vilas H.,Oruganti, Srinivas
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p. 4285 - 4294
(2017/07/03)
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- NOVEL BETULINIC SUBSTITUTED AMIDE DERIVATIVES AS HIV INHIBITORS
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The present invention relates to novel betulinic substituted amide compounds of formula (I); and pharmaceutically acceptable salts thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, X, Y, Z1, Z2, Z3 and are Formula (II) as defined herein. The invention novel betulinic substituted amide derivatives, related compounds, and pharmaceutical compositions useful for the therapeutic treatment of viral diseases and particularly HIV mediated diseases.
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Page/Page column 74-75
(2017/02/24)
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- A facile and efficient synthesis of 3,3-dimethyl isopropylidene proline from (+)-3-carene
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(Chemical Equation Presented) A highly efficient and practical route to 3,4-isopropylidene proline I, starting from (+)-3-carene, was developed. The three continuous stereocenters were constructed using the inherent chirality of the starting natural product 2. The overall yield for the 12-step synthesis is 34%. The optimized sequence leading to 1 has been successfully applied on a multigram scale, thereby establishing the practicality of this route.
- Nair, Latha G.,Saksena, Anil,Lovey, Raymond,Sannigrahi, Mousumi,Wong, Jesse,Kong, Jianshe,Fu, Xiaoyong,Girijavallabhan, Viyyoor
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experimental part
p. 1285 - 1288
(2010/04/29)
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- PROCESS FOR PRODUCING POLYCYCLIC PROLINE DERIVATIVE OR ACID ADDUCT SALT THEREOF
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A method of producing a proline derivative of the following formula (1) or an acid addition salt thereof, comprising the following four steps A to D: [wherein, any two of R1, R2, R3, R4, R5 and R6 are connected to form an optionally substituted polymethylene group having 1 to 4 carbon atoms, and R7 represents an optionally substituted linear alkyl group having 1 to 10 carbon atoms, branched alkyl group having 2 to 10 carbon atoms, linear alkenyl group having 2 to 10 carbon atoms, branched alkenyl group having 3 to 10 carbon atoms or aralkyl group having 7 to 20 carbon atoms.] (Step A) A step of reacting N-protected pyrrolidinones of the following formula (2) with a reducing agent, to produce N-protected pyrrolidinols of the following formula (3): (Step B) A step of reacting the N-protected pyrrolidinols of the formula (3) obtained in the step A with a cyanodizing agent, to produce N-protected cyanopyrrolidines of the following formula (4): (Step C) A step of reacting the N-protected cyanopyrrolidines of the formula (4) obtained in the step B with alcohols and a base, to obtain imidates of the following formula (5), and treating the imidates with an acid, to produce N-protected prolines of the following formula (6): (Step D) A step of treating the N-protected prolines of the formula (6) obtained in the step C with an acid, to produce a proline derivative of the above-described formula (1) or an acid addition salt thereof.
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Page/Page column 20
(2009/01/24)
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- Discovery of (1R,5S)-N-[3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl]-3- [2(S)-[[[(1,1-dimethylethyl)amino]carbonyl]amino]-3,3-dimethyl-1-oxobutyl]-6, 6-dimethyl-3-azabicyclo[3.1.0]hexan-2(S)-carboxamide (SCH 503034), a selective, potent, orally bioavailable hepatitis C virus NS3 protease inhibitor: A potential therapeutic agent for the treatment of hepatitis C infection
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Hepatitis C virus (HCV) infection is the major cause of chronic liver disease, leading to cirrhosis and hepatocellular carcinoma, which affects more than 170 million people worldwide. Currently the only therapeutic regimens are subcutaneous interferon-α or polyethylene glycol (PEG)-interferon-α alone or in combination with oral ribavirin. Although combination therapy is reasonably successful with the majority of genotypes, its efficacy against the predominant genotype (genotype 1) is moderate at best, with only about 40% of the patients showing sustained virological response. Herein, the SAR leading to the discovery of 70 (SCH 503034), a novel, potent, selective, orally bioavailable NS3 protease inhibitor that has been advanced to clinical trials in human beings for the treatment of hepatitis C viral infections is described. X-ray structure of inhibitor 70 complexed with the NS3 protease and biological data are also discussed.
- Venkatraman, Srikanth,Bogen, Stéphane L.,Arasappan, Ashok,Bennett, Frank,Chen, Kevin,Jao, Edwin,Liu, Yi-Tsung,Lovey, Raymond,Hendrata, Siska,Huang, Yuhua,Pan, Weidong,Parekh, Tejal,Pinto, Patrick,Popov, Veljko,Pike, Russel,Ruan, Sumei,Santhanam, Bama,Vibulbhan, Bancha,Wu, Wanli,Yang, Weiying,Kong, Jianshe,Liang, Xiang,Wong, Jesse,Liu, Rong,Butkiewicz, Nancy,Chase, Robert,Hart, Andrea,Agrawal, Sony,Ingravallo, Paul,Pichardo, John,Kong, Rong,Baroudy, Bahige,Malcolm, Bruce,Guo, Zhuyan,Prongay, Andrew,Madison, Vincent,Broske, Lisa,Cui, Xiaoming,Cheng, Kuo-Chi,Hsieh, Yunsheng,Brisson, Jean-Marc,Prelusky, Danial,Korfmacher, Walter,White, Ronald,Bogdanowich-Knipp, Susan,Pavlovsky, Anastasia,Bradley, Prudence,Saksena, Anil K.,Ganguly, Ashit,Piwinski, John,Girijavallabhan, Viyyoor,Njoroge, F. George
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p. 6074 - 6086
(2007/10/03)
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