59781-08-7Relevant academic research and scientific papers
Development of novel phenoxy-diketopiperazine-type plinabulin derivatives as potent antimicrotubule agents based on the co-crystal structure
Ding, Zhongpeng,Ma, Mingxu,Zhong, Changjiang,Wang, Shixiao,Fu, Zhangyu,Hou, Yingwei,Liu, Yuqian,Zhong, Lili,Chu, Yanyan,Li, Feng,Song, Cai,Wang, Yuxi,Yang, Jinliang,Li, Wenbao
, (2019/12/09)
The co-crystal structure of Compound 6b with tubulin was prepared and solved for indicating the binding mode and for further optimization. Based on the co-crystal structures of tubulin with plinabulin and Compound 6b, a total of 27 novel A/B/C-rings plinabulin derivatives were designed and synthesized. Their biological activities were evaluated against human lung cancer NCI-H460 cell line. The optimum phenoxy-diketopiperazine-type Compound 6o exhibited high potent cytotoxicity (IC50 = 4.0 nM) through SAR study of three series of derivatives, which was more potent than plinabulin (IC50 = 26.2 nM) and similar to Compound 6b (IC50 = 3.8 nM) against human lung cancer NCI-H460 cell line. Subsequently, the Compound 6o was evaluated against other four human cancer cell lines. Both tubulin polymerization assay and immunofluorescence assay showed that Compound 6o could inhibit microtubule polymerization efficiently. Furthermore, theoretical calculation of the physical properties and molecular docking were elucidated for these plinabulin derivatives. The binding mode of Compound 6o was similar to Compound 6b based on the result of molecular docking. The theoretical calculated LogPo/w and PCaco of Compound 6o were better than Compound 6b, which could enhance its cytostatic activity. Therefore, Compound 6o might be developed as a novel potent anti-microtubule agent.
PENICILLIN-BINDING PROTEIN INHIBITORS
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Paragraph 00329; 00386, (2019/12/15)
Described herein are certain boron-containing compounds, compositions, preparations and their use as modulators of the transpeptidase function of bacterial penicillin-binding proteins and as antibacterial agents. In some embodiments, the compounds describ
TRIAZOLO-PYRAZINE DERIVATIVES USEFUL IN THE TREATMENT OF DISORDERS OF THE CENTRAL NERVOUS SYSTEM
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Paragraph 00261, (2014/06/23)
Provided herein are heteroaryl compounds, methods of their synthesis, pharmaceutical compositions comprising the compounds, and methods of their use. In one embodiment, the compounds provided herein are useful for the treatment, prevention, and/or management of various disorders, such as CNS disorders and metabolic disorders, including, but not limited to, e.g., neurological disorders, psychosis, schizophrenia, obesity, and diabetes.
NITROGEN-CONTAINING AROMATIC HETEROCYCLYL COMPOUND
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Page/Page column 109, (2011/04/25)
The present invention provides a compound having excellent regulating action on blood lipid level. The present invention provides a compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof, etc., wherein A represents a 5-membered nitrogen-containing aromatic heterocyclyl group; R1 represents COOH or the like; each R2 represents an alkyl or the like; each R3 represents an optionally substituted phenyl, an optionally substituted phenylalkyl, or the like; m represents 0, 1, 2, or 3; n represents 0 or 1; each of R4, R5, R6, and R7 represents H, an alkyl, or the like; and B represents an optionally substituted naphthyl, an optionally substituted aromatic heterocyclyl, or a group represented by the following formula (II) wherein each of B1 and B2 represents an optionally substituted phenyl or an optionally substituted aromatic heterocyclyl.
TRIAZOLOPYRIDINE COMPOUND, AND ACTION THEREOF AS PROLYL HYDROXYLASE INHIBITOR OR ERYTHROPOIETIN PRODUCTION-INDUCING AGENT
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, (2011/04/19)
The present invention provides a triazolopyridine compound having a prolyl hydroxylase inhibitory action and an erythropoietin production-inducing ability. The present invention relates to a compound represented by the following formula [I]: wherein each symbol is as defined in the specification, or a pharmaceutically acceptable salt thereof, or a solvate thereof, as well as a prolyl hydroxylase inhibitor or erythropoietin production-inducing agent containing the compound. The compound of the present invention shows a prolyl hydroxylase inhibitory action and an erythropoietin production-inducing ability and is useful as a prophylactic or therapeutic agent for various diseases and pathologies (disorders) caused by decreased production of erythropoietin.
NITROGEN-CONTAINING FIVE-MEMBERED HETEROCYCLIC COMPOUND
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Page/Page column 83, (2010/03/02)
The present invention provides a compound represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof. The compound of the present invention has a glucokinase activity, and is useful as a medicament such as an agent for the prophylaxis or treatment of diabetes, obesity and the like, and the like.
First chiral synthesis of the N-terminal amino acid congener of nikkomycin Z based on lipase-catalyzed enantioselective acetylation of a primary alcohol possessing two stereogenic centers
Akita, Hiroyuki,Takano, Yoshiki,Nedu, Katsushi,Kato, Keisuke
, p. 1705 - 1714 (2007/10/03)
A stereoselective synthesis of a versatile chiral synthon possessing two stereogenic centers, (2S,3S)-3-[2-(5-benzyloxypyridyl)]-2-methyl-1,3-propane diol 12 (>99% ee), was achieved by using a chemo-enzymatic method. The conversion of (2S,3S)-12 to the ho
Pyridine-2-propanoic acids: Discovery of dual PPARα/γ agonists as antidiabetic agents
Humphries, Paul S.,Almaden, Jonathon V.,Barnum, Sandra J.,Carlson, Thomas J.,Do, Quyen-Quyen T.,Fraser, James D.,Hess, Mary,Kim, Young H.,Ogilvie, Kathleen M.,Sun, Shaoxian
, p. 6116 - 6119 (2008/12/20)
A series of novel pyridine-2-propanoic acids was synthesized. A structure-activity relationship study of these compounds led to the identification of potent dual PPARα/γ agonists with varied isoform selectivity. Based on the results of efficacy studies in
SELECTIVE ESTROGEN RECEPTOR MODULATORS
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Page/Page column 102, (2008/06/13)
The present invention provides a compound represented by the following formula (I); [wherein T represents a single bond, a C1-C4 alkylene group which may have a substituent and the like; formula (I-1) represents a single bond or a double bond; A represents a single bond, a bivalent 5- to 14-membered heterocyclic group which may have a substituent and the like; Y represents a single bond and the like; Z represents a methylene group and the like; ring G represents a phenylene group and the like which may condense with a 5- to 6-membered ring and may have a heteroatom; Ra and Rb are the same as or different from each other and represent a hydrogen atom and the like; W represents a single bond and the like; R' represents 1 to 4 independent hydrogen atoms and the like; and R" represents 1 to 4 independent hydrogen atoms and the like] or a salt thereof, or a hydrate thereof.
Alpha substituted carboxylic acids
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, (2008/06/13)
Alpha substituted carboxylic acids of formula (I):
