- Novel Allosteric Inhibitors of Deoxyhypusine Synthase against Malignant Melanoma: Design, Synthesis, and Biological Evaluation
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Based on the novel allosteric site of deoxyhypusine synthase (DHPS), two series of 30 novel 5-(2-methoxyphenoxy)-2-phenylpyrimidin-4-amine derivatives as DHPS inhibitors were designed and synthesized. Among them, compound8m, with the best DHPS inhibitory potency (IC50= 0.014 μM), exhibited excellent inhibition against melanoma cells, which was superior to that of GC7. Besides, molecular docking and molecular dynamics (MD) simulations further proved that compound8mwas tightly bound to the allosteric site of DHPS. Flow cytometric analysis and enzyme-linked immunosorbent assay (ELISA) showed that compound8mcould inhibit the intracellular reactive oxygen species (ROS) level. Furthermore, by western blot analysis, compound8meffectively activated caspase 3 and decreased the expressions of GP-100, tyrosinase, eIF5A2, MMP2, and MMP9. Moreover, both Transwell analysis and wound healing analysis showed that compound8mcould inhibit the invasion and migration of melanoma cells. In thein vivostudy, the tumor xenograft model showed that compound8meffectively inhibited melanoma development with low toxicity.
- Li, Shuai,Li, Xin-Yang,Li, Yu-Heng,Lin, Qi-Qi,Liu, Kai-Li,Meng, Fan-Hao,Qian, Xin-Hua,Wang, De-Pu,Xue, Wen-Han
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p. 13356 - 13372
(2021/09/20)
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- HETEROCYCLIC COMPOUND, APPLICATION THEREOF AND PHARMACEUTICAL COMPOSITION COMPRISING SAME
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Disclosed in the present invention are a heterocyclic compound, an application thereof and a pharmaceutical composition comprising the same. Provided by the present invention are a heterocyclic compound represented by formula I or a pharmaceutically acceptable salt thereof. The compound has a novel structure and a good inhibitory activity against autotaxin (ATX).
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Paragraph 0802
(2020/12/08)
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- Discovery of BR102375, a new class of non-TZD PPARγ full agonist for the treatment of type 2 diabetes
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As a potential treatment of type 2 diabetes, a novel PPARγ non-TZD full agonist, compound 18 (BR102375) was identified from the original lead BR101549 by the SAR efforts of the labile metabolite control through bioisosteres approach. In vitro assessments
- Choung, Wonken,Yang, Deokmo,Kim,Choi, Hyukjoon,Lee, Bo Ram,Park, Min,Jang, Su Min,Lim, Jae Soo,Kim, Woo Sik,Kim, Kyung-Hee,Chin, Jungwook,Jung, Kyungjin,Lee, Geumwoo,Hong,Jang, Tae-ho,Joo, Jeongmin,Hwang, Hayoung,Myung, Jayhyuk,Kim, Seong Heon
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p. 2275 - 2282
(2019/06/27)
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- The amidine using triazine compound production (by machine translation)
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[A] used in the synthesis of charge transport materials useful as the organic electroluminescent element of simple and inexpensive manufacturing method a triazine compound. Acyl amidine compound or an acid compound [a], the compound is preferably reacted in the presence of an amidine compound [...], the triazine compound of the formula illustrated in manufacture. [Drawing] no (by machine translation)
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Paragraph 0142-0143
(2018/04/20)
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- NOVEL COMPOUNDS
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This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.
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Paragraph 0467; 0468
(2013/06/27)
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- 1,2,4 -TRIAZOLES AS ALLOSTERIC MODULATORS OF MGLU5 RECEPTOR ACTIVITY FOR THE TREATMENT OF SCHIZOPHRENIA OF DEMENTIA
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This invention relates to compounds of formula (I) their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, X, R1, R2, R3 have meanings given in the description.
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Page/Page column 106
(2013/06/27)
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- SUBSTITUTED TRIAZOLES AND THEIR USE FOR TREATMENT AND/OR PREVENTION NEUROLOGICAL AND PSYCHIATRIC DISORDERS
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This invention relates to compounds of formula (I), their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R1, R2, R3 have meanings given in the description.
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Page/Page column 64
(2013/07/31)
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- NOVEL COMPOUNDS
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This invention relates to compounds of formula I their use as positive allosteric modulators of mGlu5 receptor activity, pharmaceutical compositions containing the same, and methods of using the same as agents for treatment and/or prevention of neurological and psychiatric disorders associated with glutamate dysfunction such as schizophrenia or cognitive decline such as dementia or cognitive impairment. A, B, Ar, R1, R2, R3 have meanings given in the description.
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Paragraph 0334; 0335
(2013/07/25)
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- 2-PHENYL-4-CYCLOPROPYL-PYRIMIDINE DERIVATIVES
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The present invention relates to 2-phenyl-4-cyclopropyl-pyrimidine derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular a
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Page/Page column 9
(2011/02/25)
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- Novel Biccyclic Compounds As GATA Modulators
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Novel bicyclic compounds, stereoisomers, and/or pharmaceutically acceptable salts of the novel bicyclic compounds, and/or pharmaceutically acceptable salts of the stereoisomers of the novel bicyclic compounds are provided. Additionally, methods of forming novel bicyclic compounds, stereoisomers, and/or pharmaceutically acceptable salts of the novel bicyclic compounds, and/or pharmaceutically acceptable salts of the stereoisomers of the novel bicyclic compounds are provided.
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Page/Page column 24-25
(2010/06/19)
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- 2-PHENYL-6-AMINOCARBONYL-PYRIMIDINE DERIVATIVES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS
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The invention relates to 2-phenyl-6-aminocarbonyl-pyrimidine derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention and/or treatment of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. Formula (I).
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Page/Page column 23
(2010/01/29)
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- 6-(3-AZA-BICYCLO[3.1.0]HEX-3-YL)-2-PHENYL-PYRIMIDINES
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The present invention relates to 6-(3-aza-bicyclo[3.1.0]hex-3-yl)-2-phenyl-pyrimidine derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals.
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Page/Page column 68
(2010/11/03)
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- PHOSPHONIC ACID DERIVATES AND THEIR USE AS P2Y12 RECEPTOR ANTAGONISTS
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The invention relates to 2-phenyl-pyrimidine derivatives containing a phosphonic acid motif and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. (I).
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Page/Page column 78-79
(2009/07/03)
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- 2-PHENYL-6-AMINOCARBONYL-PYRIMIDINE DERIVATIVES AND THEIR USE AS P2Y12 RECEPTOR
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The invention relates to 2-phenyl-6-aminbcarbonyl-pyrimidinc derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention and/or treatment of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular and of cerebrovascular diseases or conditions associated with platelet aggregation, including thrombosis in humans and other mammals. Formula (1).
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Page/Page column 14
(2009/12/05)
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- 2-PHENYL-4-CYCLOPROPYL-PYRIMIDINE DERIVATIVES
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The present invention relates to 2-phenyl-4-cyclopropyl-pyrimidine derivatives and their use as P2Y12 receptor antagonists in the treatment and/or prevention of peripheral vascular, of visceral-, hepatic- and renal-vascular, of cardiovascular a
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Page/Page column 24
(2009/11/29)
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- DIPEPTIDYL PEPTIDASE-IV INHIBITING COMPOUNDS, METHODS OF PREPARING THE SAME, AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME AS AN ACTIVE AGENT
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The present invention relates to novel compounds exhibiting good inhibitory activity versus Dipeptidyl Peptidase-IV(DPP-IV), methods of preparing the same and pharmaceutical compositions containing the same as an active agent.
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Page/Page column 66-67
(2010/11/24)
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- NOVEL PYRIMIDINE COMPOUNDS, PROCESS FOR THEIR PREPARATION AND COMPOSITIONS CONTAINING THEM
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The present invention provides new heterocyclic compounds, particularly substituted pyrimidines, methods and compositions for making and using these heterocyclic compounds, and methods for treating a variety of diseases and disease states, including atherosclerosis, arthritis, restenosis, diabetic nephropathy, or dyslipidemia, or disease states mediated by the low expression of Perlecan.
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Page/Page column 280-281
(2008/06/13)
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- Herbicidal 2-(hectero)aryloxy-6-arypyridines and 2-aryl-4-(hetero)aryloxypyrimidines
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New herbicidal pyridine and pyrimidine derivatives of general formula (I), STR1 wherein Z represents a nitrogen atom or a C--H group; A represents an optionally substituted aryl group or an optionally substituted 5- or 6-membered nitrogen-containing heteroaromatic group; n represents an integer from 0 to 2 and R1 or each R1 independently represents a hydrogen atom or an optionally substituted alkyl, alkoxy, alkylthio or dialkylamino group; m represents an integer from 0 to 5 and R2 or each R2 independently represents a hydrogen or a halogen atom or an optionally substituted alkyl, haloalkyl, haloalkoxy, alkoxy, alkylthio group or a nitro, cyano or a halosulphonyl group; and X represents an oxygen or sulphur atom.
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- 2-Phenyl-4-(aminomethyl)imidazoles as Potential Antipsychotic Agents. Synthesis and Dopamine D2 Receptor Binding
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A series of 2-phenyl-4-(aminomethyl)imidazoles were designed as conformationally restricted analogs of the dopamine D2 selective benzamide antipsychotics.The title compounds were synthesized and tested for blockade of YM-09151 binding in cloned African green monkey dopamine D2 receptor preparations.The binding affinity data thus obtained were compared against that of the benzamides and a previously described series of 2-phenyl-5-(aminomethyl)pyrroles.
- Thurkauf, Andrew,Hutchison, Alan,Peterson, John,Cornfield, Linda,Meade, Robin,et al.
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p. 2251 - 2255
(2007/10/02)
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- Synthesis of μ-Carbene and μ-Carbyne Complexes of Rhodium and Cobalt from Substituted Diazirines. Crystal Structures of 5-C5Me5)2(CO)2> and 5-C5Me5)2(μ-CO)(μ-C6H4Me-4)>
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The reaction of aryl(methoxy)diazirines with 5-C5Me5)2(μ-CO)2> (M = Rh or Co) affords the μ-carbene complexes 5-C5Me5)(CO)2> (R = aryl) in excellent yield.The carbonyl groups are terminal in the rhodium complexes
- Avent, Anthony G.,Benyunes, Stephen A.,Chaloner, Penny A.,Gotts, Nigel G.,Hitchcock, Peter B.
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p. 1417 - 1425
(2007/10/02)
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