- Asymmetric Michael reaction promoted by chiral thiazolidine-thiourea catalyst
-
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.
- da Silva, Tiago Lima,Rambo, Raoni Scheibler,Jacoby, Caroline Gross,Schneider, Paulo Henrique
-
supporting information
(2019/12/27)
-
- Design of Gut-Restricted Thiazolidine Agonists of G Protein-Coupled Bile Acid Receptor 1 (GPBAR1, TGR5)
-
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.
- 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)
-
- Synthesis of new thiazolidine based organocatalysts and their application to asymmetric aldol reaction
-
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.
- Cicek, Mahmut,Aydogan, Feray,Yolacan, Cigdem
-
p. 778 - 786
(2017/12/28)
-
- Small molecule diselenide additives for in vitro oxidative protein folding
-
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.
- Reddy, Post Sai,Metanis, Norman
-
supporting information
p. 3336 - 3339
(2016/02/27)
-
- BENZIDINE DERIVATIVE, METHOD FOR PREPARING SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING BENZIDINE DERIVATIVE FOR TREATING LIVER DISEASE CAUSED BY HEPATITIS C VIRUS
-
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.
- -
-
Paragraph 0177; 0178; 0179; 0180
(2016/02/24)
-
- A highly enantio- and diastereoselective direct aldol reaction in aqueous medium catalyzed by thiazolidine-based compounds
-
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).
- Rambo, Raoní Scheibler,Gross Jacoby, Caroline,Da Silva, Tiago Lima,Schneider, Paulo Henrique
-
p. 632 - 637
(2015/08/03)
-
- NON-SYSTEMIC TGR5 AGONISTS
-
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.
- -
-
Page/Page column 212
(2013/07/05)
-
- Design, synthesis of 4-aminoquinoline-derived thiazolidines and their antimalarial activity and heme polymerization inhibition studies
-
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.
- Solomon, V. Raja,Haq,Srivastava, Kumkum,Puri, Sunil K.,Katti
-
p. 619 - 626
(2013/05/09)
-
- INHIBITORS OF CYTOCHROME P450
-
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.
- -
-
Page/Page column 64-65
(2012/07/13)
-
- Thiazolidine-based organocatalysts for a highly enantioselective direct aldol reaction
-
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
- Rambo, Raoni S.,Schneider, Paulo H.
-
scheme or table
p. 2254 - 2257
(2010/11/03)
-
- Highly efficient small organic molecules for enantioselective direct aldol reaction in organic and aqueous media
-
(Chemical Equation Presented) A series of highly efficient organocatalysts have been derived from naturally available amino acids for carrying out enantioselective direct aldol reaction in both organic and aqueous medium. The aldol products were obtained in high diastereoselectivities (up to 99:1) and enantioselectivities (up to >99% ee) for a broader range of substrates using 1 mol % of a catalyst. The results demonstrate that the structural features of organocatalysts play a crucial role in obtaining high optical purity of aldol adducts in an aqueous medium. Further, the role of water in increasing the rate and enantioselectivity of the reaction has been illustrated. Moreover, the aldol products have been employed in the synthesis of chiral amino alcohols which act as useful intermediates for building up complex natural products.
- Vishnumaya, Monika Raj,Singh, Vinod K.
-
experimental part
p. 4289 - 4297
(2009/09/08)
-
- Aminoacyl-tRNA synthetase inhibitors as potent and synergistic immunosuppressants
-
The aminoacyl-tRNA synthetase family of enzymes is the target of many antibacterials and inhibitors of eukaryotic hyperproliferation. In screening analogues of 5′-O-(N-L-aminoacyl)-sulfamoyladenosine containing all 20 proteinogenic amino acids, we found t
- Van De Vijver, Pieter,Ostrowski, Tomasz,Sproat, Brian,Goebels, Jozef,Rutgeerts, Omer,Van Aerschot, Arthur,Waer, Mark,Herdewijn, Piet
-
supporting information; experimental part
p. 3020 - 3029
(2009/04/07)
-
- NEW DIPEPTIDYL PEPTIDASE IN INHIBITORS; PROCESS FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING THEM
-
The present invention relates to new dipeptidyl peptidase IV (DPP-IV) inhibitors of the formula (I), and their analogs, isomers, pharmaceutical compositions and therapeutic uses, methods of making the same.
- -
-
Page/Page column 40
(2010/02/12)
-
- Amino acid derivatives and drugs containing the same as the active ingredient
-
The present invention relates to the compounds of the formula (I) and salts thereof (all the symbols are the same meanings as described in the specification). The compounds of the formula (I) possess inhibitory activity of N-type calcium channel, so they are useful as drug for prevention and/or treatment of cerebral infarct, transient ischemic attack, encephalomyelopathy after cardiac operation, spinal angiopathy, hypertension with stress, neurosis, epilepsy, asthma and pollakiuria etc. or agent for the treatment of pain.
- -
-
-
- α-substituted hydroxamic acids as novel bacterial deformylase inhibitor-based antibacterial agents
-
We report the synthesis and biological activity of analogues of VRC3375 (N-hydroxy-3-R-butyl-3-[(2-S-(tert-butoxycarbonyl)-pyrrolidin-1-ylcarbonyl] propionamide), an orally active peptide deformylase inhibitor. This study explores the structure-activity relationship of various chelator groups, alpha substituents, P2′ and P3′ substituents in order to achieve optimal antibacterial activity with minimal toxicity liability.
- Jain,Sundram,Lopez,Neckermann,Wu,Hackbarth,Chen,Wang,Ryder,Weidmann,Patel,Trias,White,Yuan
-
p. 4223 - 4228
(2007/10/03)
-
- Design, synthesis, and pharmacological evaluation of new farnesyl protein transferase inhibitors
-
New CA1A2X peptidomimetics are described as Ras farnesyl transferase inhibitors (FTIs). They include cysteine and methionine as mimetics of the C-terminus sequence of farnesylated proteins. Furthermore, cysteine was replaced by heter
- Houssin, Raymond,Pommery, Jean,Salaün, Marie-Catherine,Deweer, Sophie,Goossens, Jean-Fran?ois,Chavatte, Philippe,Hénichart, Jean-Pierre
-
p. 533 - 536
(2007/10/03)
-
- Discovery and initial structure-activity relationships of trisubstituted ureas as thrombin receptor (PAR-1) antagonists
-
Thrombin is the most potent agonist of platelet activation, and its effects are predominantly mediated by platelet thrombin receptors. Therefore, antagonists of the thrombin receptor have potential utility for the treatment of thrombotic disorders. Screening of combinatorial libraries revealed 2 to be a potent antagonist of the thrombin receptor. Modifications of this structure produced 11k, which inhibits thrombin receptor stimulated secretion and aggregation of platelets.
- Barrow, James C,Nantermet, Philippe G,Selnick, Harold G,Glass, Kristen L,Ngo, Phung L,Young, Mary Beth,Pellicore, Janetta M,Breslin, Michael J,Hutchinson, John H,Freidinger, Roger M,Condra, Cindra,Karczewski, Jerzy,Bednar, Rodney A,Gaul, Stanley L,Stern, Andrew,Gould, Robert,Connolly, Thomas M
-
p. 2691 - 2696
(2007/10/03)
-
- Inhibitors of protein isoprenyl transferases
-
Compounds having the formula or a pharmaceutically acceptable salt thereof wherein R1is (a) hydrogen, (b) loweralkyl, (c) alkenyl, (d) alkoxy, (e) thioalkoxy, (f) halo, (g) haloalkyl, (h) aryl-L2—, and (i) heterocyclic-L2—; R2is selected from (a) (b) —C(O)NH—CH(R14)—C(O)OR15, (d) —C(O)NH—CH(R14)—C(O)NHSO2R16, (e) —C(O)NH—CH(R14)-tetrazolyl, (f) —C(O)NH-heterocyclic, and (g) —C(O)NH—CH(R14)—C(O)NR17R18; R3is substituted or unsubstituted heterocyclic or aryl, substituted or unsubstituted cycloalkyl or cycloalkenyl, and —P(W)RR3RR3′; R4is hydrogen, lower alkyl, haloalkyl, halogen, aryl, arylakyl, heterocyclic, or (heterocyclic)alkyl; L1is absent or is selected from (a) —L4—N(R5)—L5—, (b) —L4—O—L5—, (c) —L4—S(O)n—L5— (d) —L4—L6—C(W)—N(R5)—L5—, (e) —L4—L6—S(O)m—N(R5)—L5—, (f) —L4—N(R5)—C(W)—L7—L5—, (g) —L4—N(R5)—S(O)p—L7—L5—, (h) optionally substituted alkylene, (i) optionally substituted alkenylene, (j) optionally substituted alkynylene (k) a covalent bond, (l) and (m) are inhibitors of protein isoprenyl transferases. Also disclosed are protein isoprenyl transferase inhibiting compositions and a method of inhibiting protein isoprenyl transferases.
- -
-
-
- The use of Curtius rearrangement in the synthesis of 4- aminothiazolidines
-
The amine group of the L-cysteine was protected as (4R)-1,3- thiazolidines-4-carboxylic acids 2a-b and was used for the synthesis of functionalized 1,3-diamines by the way of Curtius reaction. An optimization of this methodology was made using the acylation in situ of the amine group of the thiazolidines and the activation of the carboxylic acid, after Curtius rearrangement yielded the ureas 7a,b and 8a and amine derivatives 6a,b. The Curtius reaction occurred without racemization, preserving the chemical and pharmacological importance of these products.
- Braibante, Mara E.F.,Braibante, Hugo S.,Costenaro, Edson R.
-
p. 943 - 946
(2007/10/03)
-
- Structure-activity relationship of small-sized HIV protease inhibitors containing allophenylnorstatine
-
We designed and synthesized a new class of peptidomimetic human immunodeficiency virus (HIV) protease inhibitors containing a unique unnatural amino acid, allophenylnorstatine [Apns; (2S,3S)-3-amino-2-hydroxy- 4-phenylbutyric acid], with a hydroxymethylcarbonyl (HMC) isostere as the active moiety. A systematic evaluation of structure - activity relationships for HIV protease inhibition, anti-HIV activities, and pharmacokinetic profiles has led to the delineation of a set of structural characteristics that appear to afford an orally available HIV protease inhibitor. Optimum structures, exemplified by 21f (JE-2147), incorporated 3-hydroxy-2- methylbenzoyl groups as the P2 ligand, (R)-5,5-dimethyl-1,3-thiazolidine-4- carbonyl (Dmt) residue at the P1' site, and 2-methylbenzylcarboxamide group as the P2' ligand. The present study demonstrated that JE-2147 has potent antiviral activities in vitro and exhibits good oral bioavailability and plasma pharmacokinetic profiles in two species of laboratory animals.
- Mimoto, Tsutomu,Kato, Ryohei,Takaku, Haruo,Nojima, Satoshi,Terashima, Keisuke,Misawa, Satoru,Fukazawa, Tominaga,Ueno, Takamasa,Sato, Hideharu,Shintani, Makoto,Kiso, Yoshiaki,Hayashi, Hideya
-
p. 1789 - 1802
(2007/10/03)
-
- Synthesis and Structure-Activity Relationships of a Series of Penicillin-Derived HIV Proteinase Inhibitors: Heterocyclic Ring Systems Containing P'1 and P'2 Substituents
-
As an extension of our earlier work based upon a single penicillin-derived thiazolidine moiety we have found that the decahydroisoquinoline grouping, also present in Ro 31-8959, is an effective replacement for one of the thiazolidine units in C2 symmetric penicillin-derived dimers.Reaction of racemic epoxide 6 with -decahydro-N-(1,1-dimethylethyl)-3-isoquinolinecarboxamide gave diastereoisomers 34a and 34b.The stereochemistry of the hydroxyl grouping of 34a was determined to be (S).Reaction of the amines derived from 34a and 34b with thiazolidine 8a gave 50 and 51, respectively.Compound 50 was a potent inhibitor of HIV proteinase (IC50 = 23 nM) with antiviral activity against HIV-1 in vitro (EC50 C8166 cells = 50 nM).However, a poor pharmacokinetic profile in the dog for compound 50 and its analogues, in keeping with earlier studies on penicillin-derived dimers in three species, precluded their development as potential antivirals.
- Kitchin, John,Bethell, Richard C.,Cammack, Nicholas,Dolan, Simon,Evans, Derek N.,et al.
-
p. 3707 - 3716
(2007/10/02)
-
- Synthesis and NMR studies of thiazolidine-4-carboxylic acid derivatives containing a nitro ester function
-
The preparation of thiazolidine-4-carboxylic acid derivatives containing a 2-nitrooxyethylamine group, potentially active as vasodilators, is reported. Their 1H nmr studies carried out to establish the configuration of the C2 stereocenter and t
- Benedini,Ferrario,Sala,Sala,Soresinetti
-
p. 1343 - 1347
(2007/10/02)
-
- Synthesis and radioprotective activity of new N-(amino acid)-S-acetylcysteamine and cystamine derivatives
-
In order to evaluate the influence of an amino acid conjugation (Sar,Ser, Phe, Pro, Thz) on S-acetylcysteamine, cystamine, N-(amino acid)-S-acetylcysteamine (14-18) and N,N'-bis (amino acid) cystamine (24-28) derivatives have been synthesized and evaluated as potential radioprotectors. Their toxicity and radioprotective activity, as the dose reduction factor (DRF) have been determined (in vivo; ip) and compared with cysteamine and cystamine parent compounds: N-glycyl-S-acetylcysteamine trifluoroacetate 1 and N,N'-bis (glycyl)cystamine bis (trifluoroacetate) 2. Among these compounds, 14 (Sar), 15 (Ser), 15a [Ser (Ac)], 16 [Phe], 24 (Sar) had significant radioprotective activity.
- Oiry,Pue,Fatome,Sentenac-Roumanou,Lion,Imbach
-
p. 809 - 817
(2007/10/02)
-
- Amino acid derivatives having anti-tumor activity and compositions containing them
-
Amino acid amides of formula (I): STR1 wherein R1 -R5 and Y represent a variety of organic groups and atoms (including where R2, Y and the adjacent nitrogen atom together represent a thiazolidine or pyrrolidine group) and X represents carbonyl or sulfonyl are mostly new compounds and have valuable anti-tumor and immuno-regulatory activities. They may be formulated in compositions for pharmaceutical use.
- -
-
-
- [4R]-3-(Omega-AROYLPROPIONYL)-4-THIAZOLIDINECARBOXYLIC ACIDS AND ESTERS
-
This disclosure describes novel 4R!-3-(ω-aroylpropionyl)-4-thiazolidinecarboxylic acids and esters and the cationic salts thereof which are useful as hypotensive agents in mammals.
- -
-
-
