141629-19-8Relevant articles and documents
Synthesis of nature product kinsenoside analogues with anti-inflammatory activity
Song, Wei,Sun, Yong,Xu, Lintao,Sun, Yajing,Li, Tianlu,Peng, Peng,Lou, Hongxiang
supporting information, (2020/12/02)
Kinsenoside is the major bioactive component from herbal medicine with a broad range of pharmacological functions. Goodyeroside A, an epimer of kinsenoside, remains less explored. In this report we chemically synthesized kinsenoside, goodyeroside A and their analogues with glycan variation, chirality inversion at chiral center(s), and bioisosteric replacement of lactone with lactam. Among these compounds, goodyeroside A and its mannosyl counterpart demonstrated superior anti-inflammatory efficacy. Furthermore, goodyeroside A was found to suppresses inflammatory through inhibiting NF-κB signal pathway, effectively. Structure-activity relationship is also explored for further development of more promising kinsenoside analogues as drug candidates.
MODULATORS OF G-PROTEIN COUPLED RECEPTORS
-
Page/Page column 225, (2019/10/15)
This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt and/or hydrate and/or prodrug of the compound) that modulate (e.g., agonize or partially agonize or antagonize) glucagon?like peptide?1 receptor ("GLP?1R") and/or the gastric inhibitory polypeptide receptor ("GIPR"). The chemical entities are useful, e.g., for treating a subject (e.g., a human) having a disease, disorder, or condition in which modulation (e.g., agonism, partial agonism or antagonism) of GLP?1R and/or GIPR activities is benficial for the treatment or prevention of the underlying pathology and/or symptoms and/or progression of the disease, disorder, or condition. In some embodiments, the modulation results in an enhancment of (e.g., an increase in) existing levels (e.g., normal or below normal levels) of GLP?1R and/or GIPR activity (e.g., signaling). In some embodiments, the chemical entities described herein further modulate (e.g., attenuate, uncouple) -arrestin signaling relative to what is observed with the native ligand. This disclosure also features compositions as well as other methods of using and making the said chemical entities.
Method for preparing intelligence-improving medicine (S)-oxiracetam
-
Paragraph 0037-0039, (2017/04/28)
The invention discloses a method for preparing an intelligence-improving medicine (S)-oxiracetam. The method comprises the following steps: (1) under the catalysis of 4-dimethylaminopyridine, enabling 2-oxiraneisobutylacetate to contact with ammonia gas to react, so as to obtain (S)-4-hydroxyl-2-oxopyrrolidine; (2) enabling the (S)-4-hydroxyl-2-oxopyrrolidine obtained by the step (1) to react with tert-butyldimethylsilyl chloride, so as to obtain a compound shown as a formula III, which is protected by tert-butyl dimethylsilane; (3) enabling the compound shown as the formula III and 2-bromoacetic ester to be subjected to a nucleophilic reaction under an alkaline condition, so as to obtain a compound shown as a formula IV; (4) under the catalysis of ammonium chloride, enabling the compound shown as the formula IV and ammonia gas to be subjected to an ammonolysis reaction, so as to obtain the (S)-oxiracetam as shown in the description. The (S)-oxiracetam prepared by the method provided by the invention is high in yield, high in ee value and relatively low in cost, and a preparation process is simple and is suitable for industrial production.
Preparation method of (S)-oxiracetam
-
Paragraph 0035-0037, (2017/07/12)
The invention discloses a preparation method of (S)-oxiracetam. The preparation method is characterized by comprising the following steps that 1, 2-epoxy ethylacetamide is cyclized in molecules in the presence of a catalyst and alkali to obtain a compound (S)-3-hydroxyl-butyrolactam shown as a formula II; 2, the (S)-3-hydroxyl-butyrolactam obtained in the step 1 reacts with tertiary butyl methyl chlorosilane to obtain a compound protected by the tertiary butyl methyl chlorosilane and shown as a formula III; 3, the compound shown as the formula III performs nucleophilic reaction with bromoacetonitrile under the alkaline condition to obtain a N-cyanomethide shown as a formula IV; 4, the N-cyanomethide shown as the formula IV is subjected to hydrolysis under the acid condition to obtain the (S)-oxiracetam (shown in the description). The method adopts conventional non-achiral raw materials and is low in cost, the (S)-oxiracetam is high in yield, an ee value is high, and a new way is provided for preparation of the (S)-oxiracetam.
NOVEL THIOPHENECARBOXAMIDE DERIVATIVE AND PHARMACEUTICAL USE THEREOF
-
Page/Page column 13; 14, (2012/05/04)
The object of the present invention is to provide a compound having a glucokinase-activating effect. A pharmaceutical composition comprising a compound represented by the general formula (I) or a pharmaceutically acceptable salt thereof as an active ingredient: wherein X means a nitrogen atom or CR6, wherein R6 means a hydrogen atom or a halogen atom; R1 means a hydrogen atom, a C1-C6 alkyl group, a C1-C6 alkoxy group or a C1-C6 alkylthio group; R2 means a hydrogen atom or a fluorine atom; R3 means a hydrogen atom or a C1-C6 alkyl group; and one of R4 and R5 means a hydrogen atom or a C1-C6 alkyl group, and the other means a C1-C6 alkylenecarboxylic acid, a C1-C6 alkylsulfonyl group, a C1-C6 alkylcarbonyl group, or CONH2.
AMIDE COMPOUNDS USEFUL IN THERAPY
-
Page/Page column 157, (2010/04/25)
A compound of Formula (I), or a pharmaceutically acceptable salt or solvate thereof, (I) wherein, R1 and R2 each independently represent H, halogen, CF3, C1-3 alkyl or C1-3 alkoxy; R3 represents C1-6 alkyl, C3-6 cycloalkyl, phenyl (optionally substituted by one or more substituents each independently selected from Ra) or Het (optionally substituted by one or more substituents each independently selected from OH, oxo, or C1-4 alkyl); R4 represents H or C1-3 alkyl; R5 represents C1-6 alkyl (optionally substituted by one or more substituents each independently selected from Rb), C3-6 cycloalkyl (optionally substituted by one or more substituents each independently selected from oxo or OH), or Het2 (optionally substituted by one or more substituents each independently selected from Rd); oxygen atom or 1 sulphur atom, or (c) 1 oxygen atom or 1 sulphur atom, (optionally substituted by one or more substituents each independently selected from OH, oxo or C1-4 alkyl); and R6 represents C1-3 alkyl (optionally substituted by one or more substituents each independently selected from Rf), C3-5 cycloalkyl (optionally substituted by one or more halogen), CN or halogen; where Rf represents halogen or phenyl: and compositions, processes for the preparation, and uses thereof, e.g. in the treatment of endometriosis or uterine fibroids.
Nonracemic bicyclic lactam lactones via regio- and cis-diastereocontrolled C-H insertion. Asymmetric synthesis of (8S,8aS)-octahydroindolizidin-8-ol and (1S,8aS)-octahydroindolizidin-1-ol
Wee, Andrew G. H.,Fan, Gao-Jun,Bayirinoba, Hypolite M.
supporting information; experimental part, p. 8261 - 8271 (2010/02/17)
(Chemical Equation Presented) The Rh2(MPPIM)4- catalyzed intramolecular C-H insertion reaction of (S)- and (R)-1-benzyl-5-(R- diazoacetoxy)piperidin-2-one and (S)-1-benzyl-4-(α-diazoacetoxy) pyrrolidin-2-one proceeds with high regios
ARYLOXY-SUBSTITUTED BENZIMIDAZOLE DERIVATIVES
-
Page/Page column 72, (2010/11/28)
A glucokinase activator is provided; and a treatment and/or a preventive for diabetes, or a treatment and/or a preventive for diabetes such as retinopathy, nephropathy, neurosis, ischemic cardiopathy, arteriosclerosis, and further a treatment and/or a preventive for obesity are provided. The invention relates to a compound of a formula (I): [wherein R1 and R2 represent a hydrogen, etc.; R3 represents a hydrogen atom, a halogen atom, etc.; R4 each independently represents a hydrogen atom, a lower alkyl group, etc.; Q represents a carbon atom, a nitrogen atom or a sulfur atom (the sulfur atom may be mono- or di-substituted with an oxo group); R5 and R6 each represent a hydrogen atom, a lower alkyl group, etc.; X1, X2, X3 and X4 each independently represent a carbon atom or a nitrogen atom; Z represents an oxygen atom, a sulfur atom or a nitrogen atom; Ar represents an aryl or heteroaryl group optionally mono to tri-substituted with a group selected from the substituent group β; ring A represents a 5- or 6-membered nitrogen-containing heteroaromatic group; m indicates an integer of from 1 to 6; n indicates an integer of from 0 to 3; p indicates an integer of from 0 to 2 (provided that at least two of X1 to X4 are carbon atoms); q indicates 0 or 1] or its pharmaceutically-acceptable salt, which has an effect of glucokinase activation and is useful as a treatment for diabetes.
Regio- and diastereocontrolled C-H insertion of chiral γ- and δ-lactam diazoacetates. Application to the asymmetric synthesis of (8S,8aS)-8-hydroxyindolizidine
Fan, Gao-Jun,Wang, Zhongyi,Wee, Andrew G. H.
, p. 3732 - 3734 (2007/10/03)
γ- and δ-Lactam diazoacetates undergo efficient intramolecular C-H insertion catalyzed by Rh2(MPPIM)4 with excellent regioselectivity and cis-diastereoselectivity to provide synthetically useful bicyclic lactam lactones. The Royal So
Trials for the synthesis of (R)-4-mercapto-pyrrolidin-2-one ((R)-MPD)
Kobayashi, Satoshi,Kobayashi, Katsuhiro,Hirai, Koichi
, p. 909 - 912 (2007/10/03)
Several trials were made for the syntheses of (S)-4-hydroxy-pyrrolidin- 2-one ((S)-HPD) and (R)-4-mercapto-pyrrolidin-2-one ((R)-MPD), a substituent at the 2-position of the orally active carbapenem antibiotic CS-834. The latter was synthesized from prochiral dimethyl or diethyl 3-p- methoxybenzylthioglutarate using pig liver esterase technology to give monoester with an optical purity of 51-71% e.e. as a key intermediate.
