39994-75-7Relevant articles and documents
Stereoselective cycloaddition of monosubstituted ketene to a methyl glyoxylate- and threonine-derived imine: Synthesis of optically pure β-lactamic α-amino ester with high functionality
Mignani,Mouysset,Le Roy,Stella
, p. 3685 - 3691 (2000)
The reaction of chloroacetyl chloride and triethylamine with a chiral imine derived from the combination of methyl glyoxylate and protected L-threonine gave two optically active α-amino acid derivatives with a cis-substituted β-lactam skeleton in a 72:28 ratio. The major product is obtained in 59% yield by simple crystallisation.
(2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative as well as preparation method and application thereof
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Paragraph 0047-0048; 0054-0056, (2021/02/10)
The invention discloses a (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative shown as a formula (I) or an optical isomer, a diastereomer and racemate mixture and pharmaceutically acceptable salt thereof as well as a preparation method and application of the (2S, 3R)-3-amino-2-hydroxy-4-phenylbutyrylamide derivative. It is shown by comparison of results of a positive control group and a model group on lymphedema prevention experiments that the compound disclosed in the invention shows obvious anti-edema activity.
NOVEL COMPOUNDS AND THEIR USE
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Page/Page column 76-77, (2021/06/26)
The present invention provides compounds of the general formula (I) or a pharmaceutically acceptable prodrugs, salts and/or solvates thereof, wherein LHS is selected from the group consisting of LHSa and LHSb And wherein, the asterisk (*) marks the point of attachment; These compounds exhibit antibacterial activity against Gram-negative and Gram-positive bacteria, especially S. aureus, E. coli, K. pneumoniae and A. baumannii. Pharmaceutical compositions containing these compounds, therapeutic uses thereof and methods for manufacturing the same are also provided.
Bicyclic Lactams Derived from Serine or Cysteine and 2-Methylpropanal
Bagum, Halima,Christensen, Kirsten E.,Genov, Miroslav,Moloney, Mark G.,Pretsch, Alexander,Pretsch, Dagmar,Shire, Bethany R.
supporting information, p. 378 - 382 (2020/02/27)
Bicyclic lactams may be prepared from serine or cysteine and 2-methylpropanal; the resulting S, N -heterocycles are more stable than the corresponding O, N -heterocycles but both are synthetic intermediates capable of further elaboration.
Amino acid conjugates of 2-mercaptobenzimidazole provide better anti-inflammatory pharmacology and improved toxicity profile
Khan, Muhammad T.,Nadeem, Humaira,Khan, Arif-ullah,Abbas, Muzaffar,Arif, Muazzam,Malik, Nadia Shamshad,Malik, Zulkifal,Javed, Ibrahim
, p. 1057 - 1072 (2020/08/13)
Benzimidazole is an important pharmacophore for clinically active drugs against inflammation and treatment of pain, however, it is associated with gastrointestinal side effects. Here we synthesized benzimidazole based agents with significant analgesic/anti-inflammatory potential but with less gastrointestinal adverse effects. In this study, we synthesized novel, orally bioavailable 2-mercaptobenzimidazole amino acid conjugates (4a–4o) and screened them for analgesic, anti-inflammatory and gastro-protective effects. The synthesized 2-mercaptbenzimidazole derivatives were characterized for their structure using FTIR, 1H NMR and 13C NMR spectroscopic techniques. The 2-mercaptobenzimidazole amino acid conjugates have found to possess potent analgesic, anti-inflammatory and gastroprotective activities, particularly with compound 4j and 4k. Most of the compounds exhibited remarkable anti-ulcer and antisecretory effects. Molecular docking studies were carried out to study the binding affinities and interactions of the synthesized compounds with target proteins COX-2 (PDB ID: 3LN1) and H+/K+-ATPase (PDB ID: 5Y0B). Our results support the clinical promise of these newly synthesized 2-mercaptobezimidazol conjugates as a component of therapeutic strategies for inflammation and analgesia, for which the gastric side effects are always a major limitation.
A Novel N-Substituted Valine Derivative with Unique Peroxisome Proliferator-Activated Receptor γbinding Properties and Biological Activities
Peiretti, Franck,Montanari, Roberta,Capelli, Davide,Bonardo, Bernadette,Colson, Cécilia,Amri, Ez-Zoubir,Grimaldi, Marina,Balaguer, Patrick,Ito, Keiichi,Roeder, Robert G.,Pochetti, Giorgio,Brunel, Jean Michel
, p. 13124 - 13139 (2020/12/02)
A proprietary library of novel N-Aryl-substituted amino acid derivatives bearing a hydroxamate head group allowed the identification of compound 3a that possesses weak proadipogenic and peroxisome proliferator-Activated receptor γ(PPARI) activating properties. The systematic optimization of 3a, in order to improve its PPARγagonist activity, led to the synthesis of compound 7j (N-Aryl-substituted valine derivative) that possesses dual PPARI/PPARα agonistic activity. Structural and kinetic analyses reveal that 7j occupies the typical ligand binding domain of the PPARγagonists with, however, a unique high-Affinity binding mode. Furthermore, 7j is highly effective in preventing cyclin-dependent kinase 5-mediated phosphorylation of PPARγserine 273. Although less proadipogenic than rosiglitazone, 7j significantly increases adipocyte insulin-stimulated glucose uptake and efficiently promotes white-To-brown adipocyte conversion. In addition, 7j prevents oleic acid-induced lipid accumulation in hepatoma cells. The unique biochemical properties and biological activities of compound 7j suggest that it would be a promising candidate for the development of compounds to reduce insulin resistance, obesity, and nonalcoholic fatty liver disease.
L-threonine-linked dihydroartemisinin-fluoroquinolone conjugates, intermediates thereof, and preparation methods and uses of conjugates and intermediates
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Paragraph 0113-0119, (2019/12/08)
The invention discloses L-threonine-linked dihydroartemisinin-fluoroquinolone conjugates represented by formula I, intermediates represented by formula II, preparation methods of the compounds of formula I and formula II, and uses of the compounds of the formula I in the preparation of drugs for resisting mycobacterium tuberculosis or/and drugs for lowering blood lipids.
Polypeptide raw material N-fluorenylmethoxycarbonyl-O-tert-butyl threonine preparation method
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Paragraph 0012-0014, (2019/01/23)
The invention discloses a polypeptide raw material N-fluorenylmethoxycarbonyl-O-tert-butyl threonine preparation method, and mainly solves the technical problems of complexity, long cycle, more wastegas, waste water and industrial residues, high cost, high dangerousness and the like in an original process. The preparation method includes the steps: first, suspending threonine in methanol, reducing temperature, dropping thionyl chloride and then removing solvents by concentration after temperature reaction to obtain threonine methyl ester hydrochloride; second, dissolving the threonine methylester hydrochloride in methylene dichloride, leading in isobutene, concentrating sulfuric acid and performing sealed reaction treatment to obtain oily O-tert-butyl threonine methyl ester; third, dissolving the O-tert-butyl threonine methyl ester in water and acetone, adding sodium hydroxide, enabling pH (potential of hydrogen) to be 11-12, performing reaction to obtain O-tert-butyl threonine solution, adding 9-fluorenylmethyl-N-succinimidyl carbonate, maintaining the pH of 8-9 of a system by the aid of alkali liquor, performing washing acidification extraction after reaction and performing treatment to obtain N-fluorenylmethoxycarbonyl-O-tert-butyl threonine serving as a final product.
IMMUNOPROTEASOME INHIBITORS
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Paragraph 0243, (2019/06/13)
Provided herein are compounds, such as a compound of Formula (I), or a pharmaceutically acceptable salt thereof, that are immunoproteasome (such as LMP2 and LMP7) inhibitors. The compounds described herein can be useful for the treatment of diseases treatable by inhibition of immunoproteasomes. Also provided herein are pharmaceutical compositions containing such compounds and processes for preparing such compounds.
Synthetic Access to 3-Substituted Pyroglutamic Acids from Tetramate Derivatives of Serine, Threonine, allo-Threonine, and Cysteine
Bagum, Halima,Christensen, Kirsten E.,Genov, Miroslav,Pretsch, Alexander,Pretsch, Dagmar,Moloney, Mark G.
, p. 10257 - 10279 (2019/08/20)
A general route which provides direct access to pyroglutamates from tetramates, making use of Suzuki coupling on an enol mesylate, followed by reduction, is reported. This work permits direct scaffold hopping from tetramate to substituted pyroglutamates. Some compounds in the library showed modest antibacterial activity against Gram-positive bacteria.