- An Efficient Synthesis of (4S)-(-)-4-Isopropyl-2-oxazolidinone
-
A new, efficient, cost-effective method for the preparation of the Evans'chiral auxiliary (4S)-4-isopropyl-2-oxazolidinone (4) is described.A Schotten-Baumann acylation of valine with phenyl carbonochloridate quantitatively affords the protected valine, which is then reduced with borane in tetrahydrofuran to give an alcohol.Cyclization with a catalytic amount of potassium tert-butoxide gives 4 in 81percent overall yield and in 41-43percent after crystallization from ethyl acetate/n-hexane.
- Wuts, Peter G. M.,Pruitt, Lynn E.
-
-
Read Online
- Synthesis of HIV protease inhibitor ABT-378 (lopinavir)
-
A large scale process for the synthesis of HIV protease inhibitor candidate ABT-378 has been developed which utilizes an intermediate common to the synthesis of ritonavir, Abbott's first generation compound. The synthesis relies on the sequential acylation of this intermediate which is carried through as a mixture of diastereomers until the penultimate step. A synthesis of acid 5, derived from L-valine, is also reported.
- Stoner, Eric J.,Cooper, Arthur J.,Dickman, Daniel A.,Kolaczkowski, Lawrence,Lallaman, John E.,Liu, Jih-Hua,Oliver-Shaffer, Patricia A.,Patel, Ketan M.,Paterson Jr., Joseph B.,Plata, Daniel J.,Riley, David A.,Sham, Hing L.,Stengel, Peter J.,Tien, Jien-Heh J.
-
-
Read Online
- A novel, potent, and orally bioavailable thiazole HCV NS5A inhibitor for the treatment of hepatitis C virus
-
A medicinal chemistry program based on the small-molecule HCV NS5A inhibitor daclatasvir has led to the discovery of dimeric phenylthiazole compound 8, a novel and potent HCV NS5A inhibitor. The subsequent SAR studies and optimization revealed that the cycloalkyl amide derivatives 27a-29a exhibited superior potency against GT1b with GT1b EC50 values at picomolar concentration. Interestingly, high diastereospecificity for HCV inhibition was observed in this class with the (1R,2S,1′R,2′S) diastereomer displaying the highest GT1b inhibitory activity. The best inhibitor 27a was found to be 3-fold more potent (GT1b EC50 = 0.003 nM) than daclatasvir (GT1b EC50 = 0.009 nM) against GT1b, and no detectable in vitro cytotoxicity was observed (CC50 > 50 μM). Pharmacokinetic studies demonstrated that compound 27a had an excellent pharmacokinetic profiles with a superior oral exposure and desired bioavailability after oral administration in both rats and dogs, and therefore it was selected as a developmental candidate for the treatment of HCV infection.
- Yeh, Teng-Kuang,Kang, Iou-Jiun,Hsu, Tsu-An,Lee, Yen-Chun,Lee, Chung-Chi,Hsu, Sheng-Ju,Tian, Ya-Wen,Yang, Hui-Yun,Chen, Chiung-Tong,Chao, Yu-Sheng,Yueh, Andrew,Chern, Jyh-Haur
-
p. 245 - 268
(2019/02/19)
-
- SPIRO COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS
-
Disclosed are spiro compounds of formula (I), or stereomers, geometric isomers, tautomers, nitrogen oxides, hydrates, solvates, metabolites, pharmaceutically acceptable salts or prodrugs thereof. The compounds can be used to treat hepatitis C virus (HCV) infection or hepatitis C disease. Furthermore disclosed are pharmaceutical compositions containing the compounds and the method of using the compounds or pharmaceutical compositions in the treatment of HCV infection or hepatitis C disease.
- -
-
Paragraph 0378; 0563; 0571
(2015/11/09)
-
- BRIDGED RING COMPOUNDS AS HEPATITIS C VIRUS INHIBITORS, PHARMACEUTICAL COMPOSITIONS AND USES THEREOF
-
Provided herein is a compound of formula (I) or a stereoisomer, a geometric isomer, 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 HCV infection or a HCV disorder. Also provided herein are a pharmaceutical composition comprising the compound and the use of the compound and the pharmaceutical composition thereof, which can also be used for treating HCV infection or a HCV disorder.
- -
-
Page/Page column 151
(2014/09/16)
-
- Phosgene-free synthesis of polypeptides: Useful synthesis for hydrophobic polypeptides through polycondensation of activated urethane derivatives of α-amino acids
-
We report a useful synthetic method of polypeptides using a series of urethane derivative of α-amino acids (l-leucine, l-phenylalanine, l-valine, l-alanine, l-isoleucine, l-methionine), which are readily synthesized by N-carbamoylation of tetrabutylammoni
- Yamada, Shuhei,Koga, Koichi,Sudo, Atsushi,Goto, Mitsuaki,Endo, Takeshi
-
p. 3726 - 3731
(2013/09/02)
-
- Retroviral protease inhibiting compounds
-
A compound comprising a substituent of the formula (II) is disclosed as an HIV protease inhibitor. Intermediates for making such compounds and processes for making such intermediates are also disclosed.
- -
-
-
- Process for the preparation of an activated amino acid
-
A process is disclosed for the preparation of an N-acylated activated derivative of an amino acid or a salt thereof.
- -
-
-
- Process for the preparation of a disubstituted thiazole
-
A process is disclosed for the preparation of N-((N-Methyl-N-((2-isopropyl-4-thiazolyl)methyl)amino)carbonyl)-amino acid derivatives.
- -
-
-