51077-16-8Relevant articles and documents
Asymmetric Michael reaction promoted by chiral thiazolidine-thiourea catalyst
da Silva, Tiago Lima,Rambo, Raoni Scheibler,Jacoby, Caroline Gross,Schneider, Paulo Henrique
supporting information, (2019/12/27)
In this work, we report the synthesis and characterization of three new thiazolidine- and thiourea-based chiral organocatalysts. These compounds were successfully applied in asymmetric Michael addition reactions between different ketones and nitrostyrenes leading to products in up to 85% yield, >96:4 r.d. and 97% e.e. Computational studies were used to better visualize the proposed transition state and explain the observed stereoselectivities. One of the new catalysts was also successfully applied in an aldol addition between cyclohexanone an p-nitrobenzaldehyde leading to product in 80% yield, >96:4 d.r. and 80% e.e.
Design of Gut-Restricted Thiazolidine Agonists of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5)
Chen, Tao,Reich, Nicholas William,Bell, Noah,Finn, Patricia D.,Rodriguez, David,Kohler, Jill,Kozuka, Kenji,He, Limin,Spencer, Andrew G.,Charmot, Dominique,Navre, Marc,Carreras, Christopher W.,Koo-Mccoy, Samantha,Tabora, Jocelyn,Caldwell, Jeremy S.,Jacobs, Jeffrey W.,Lewis, Jason Gustaf
supporting information, p. 7589 - 7613 (2018/09/12)
Bile acid signaling and metabolism in the gastrointestinal tract have wide-ranging influences on systemic disease. G protein-coupled bile acid receptor 1 (GPBAR1, TGR5) is one of the major effectors in bile acid sensing, with demonstrated influence on metabolic, inflammatory, and proliferative processes. The pharmacologic utility of TGR5 agonists has been limited by systemic target-related effects such as excessive gallbladder filling and blockade of gallbladder emptying. Gut-restricted TGR5 agonists, however, have the potential to avoid these side effects and consequently be developed into drugs with acceptable safety profiles. We describe the discovery and optimization of a series of gut-restricted TGR5 agonists that elicit a potent response in mice, with minimal gallbladder-related effects. The series includes 12 (TGR5 EC50: human, 143 nM; mouse, 1.2 nM), a compound with minimal systemic availability that may have therapeutic value to patients with type 2 diabetes mellitus, nonalcoholic steatohepatitis, or inflammatory bowel disease.
Synthesis of new thiazolidine based organocatalysts and their application to asymmetric aldol reaction
Cicek, Mahmut,Aydogan, Feray,Yolacan, Cigdem
, p. 778 - 786 (2017/12/28)
Background: Proline and its derivatives are versatile organocatalysts for many reactions. Especially prolinamide derivatives have been prepared and investigated in aldol reaction successfully. Generally, derivatizations have been made on side chain of proline to develop new effective catalysts. But, there are only few examples of different cyclic systems other than pyrrolidine ring used as chiral organocatalysts. Method: The methodology for this study was the synthesis of new thiazolidine-4-carboxylic acid based organocatalysts and investigation of their catalytic activities in asymmetric direct aldol reactions. Results: New thiazolidine based organocatalysts 6a-g [substituted (4R)-N-[(2S)-1-amino-1-oxo-3-phenyl-2-propyl]-4-thiazolidinecarboxamides] were synthesized and characterized. Their catalytic activity studies in asymmetric direct aldol reactions of aliphatic ketones with arylaldehydes were performed. Among the catalysts investigated in this study, especially methyl (2S)-3-phenyl-2-[(2S)-3-phenyl-2-[(4R)-thiazolidine-4-carboxamido]propanamido]propanoate (6a) and (4R)-N-[(2S)-1-(benz-hydrylamino)-1-oxo-3-phenyl-2-propyl]-4-thiazolidinecarboxamide (6b) gave the best diastereoselectivities (up to 91%), enantioselectivities (up to 88%) and yields (up to 94%) when different aliphatic ketones and aromatic aldehydes with electron withdrawing groups were used. Conclusion: Some new organocatalysts derived from thiazolidine-4-carboxylic acid were designed, synthesized, and successfully used in the direct asymmetric aldol reaction of aliphatic ketones and aromatic aldehydes under solvent free conditions. The results showed that these new products were promising organocatalysts for aldol reaction.
BENZIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING BENZIDINE DERIVATIVE FOR TREATING LIVER DISEASE CAUSED BY HEPATITIS C VIRUS
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Paragraph 0177; 0178; 0179; 0180, (2016/02/24)
The disclosed compounds have antiviral activity against C-type virus, an optical isomer thereof, a pharmaceutically acceptable salt thereof, a method for preparing the same, and a pharmaceutical composition containing the same as an active ingredient for preventing or treating liver disease caused by hepatitis C virus. The benzidine derivative according to the present invention has excellent antiviral activity against hepatitis C virus and exhibits excellent medicinal activity in the living body, and thus the pharmaceutical composition containing the same as an active ingredient can be useful as a pharmaceutical composition for preventing or treating liver disease, such as acute hepatitis C, chronic hepatitis C, cirrhosis, or hepatocellular carcinoma, caused by C-type virus.
Small molecule diselenide additives for in vitro oxidative protein folding
Reddy, Post Sai,Metanis, Norman
supporting information, p. 3336 - 3339 (2016/02/27)
The in vitro oxidative folding of disulfide-rich proteins can be challenging. Here we show a new class of small molecule diselenides, which can be easily prepared from inexpensive starting materials, used to enhance oxidative protein folding. These compounds were tested on a model protein, bovine pancreatic trypsin inhibitor. Two of the tested diselenides showed considerable improvement over glutathione and were on par with the previously described selenoglutathione.
A highly enantio- and diastereoselective direct aldol reaction in aqueous medium catalyzed by thiazolidine-based compounds
Rambo, Raoní Scheibler,Gross Jacoby, Caroline,Da Silva, Tiago Lima,Schneider, Paulo Henrique
, p. 632 - 637 (2015/08/03)
Taking l-aminoacids as starting materials, a new set of enantiopure thiazolidine-based organocatalysts were prepared using a simple synthetic approach and successfully applied in the asymmetric direct aldol reaction between various cyclic ketones and aldehydes in a saturated aqueous medium. The aldol adducts were obtained with excellent enantioselectivity (up to >99% ee) and diastereoselectivity (dr >20:1).
NON-SYSTEMIC TGR5 AGONISTS
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Page/Page column 212, (2013/07/05)
Compounds of structure (I), or a stereoisomer, tautomer, pharmaceutically acceptable salt or prodrug thereof, wherein R1, R2, R3, R4, R8, R9, R10, R11, R12, A1, A2, X, Y and Z are as defined herein. Uses of such compounds as TGR5 antagonists and for treatment of various indications, including Type II diabetes meletus are also provided.
Design, synthesis of 4-aminoquinoline-derived thiazolidines and their antimalarial activity and heme polymerization inhibition studies
Solomon, V. Raja,Haq,Srivastava, Kumkum,Puri, Sunil K.,Katti
, p. 619 - 626 (2013/05/09)
The present study describes the synthesis of a series of new 4-aminoquinoline-derived thiazolidines and evaluation of their antimalarial activity against a NF-54 strain of Plasmodium falciparum in vitro and N-67 strain of Plasmodium yoelii in vivo. Among the series, two compounds, 2-(4-chloro-phenyl)-thiazolidine-4-carboxylic acid [2-(7-chloro-quinolin-4- ylamino)-ethyl]-amide hydrochloride (14) and 2-(2,6-dichloro-phenyl)- thiazolidine-4-carboxylic acid [2-(7-chloro-quinolin-4-ylamino)-ethyl]-amide hydrochloride (22) exhibited significant suppression of parasitaemia in the in vivo assay. All the analogues were found to form strong complex with haematin and inhibited the β-haematin formation in vitro. These results suggest that these compounds act on heme polymerization target.
INHIBITORS OF CYTOCHROME P450
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Page/Page column 64-65, (2012/07/13)
The present application provides for a compound of formula I, or a salt thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods that include the administration of such compounds with at least one additional therapeutic agent.
Thiazolidine-based organocatalysts for a highly enantioselective direct aldol reaction
Rambo, Raoni S.,Schneider, Paulo H.
scheme or table, p. 2254 - 2257 (2010/11/03)
A set of enantiopure thiazolidine-based organocatalysts have been synthesized from l-cysteine, in a straightforward manner allowing numerous structural variations. In particular, organocatalyst 3a exhibits the highest catalytic performance working in an a
