- Wnt signal pathway inhibitor and use thereof
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The invention relates to heterocyclic compounds with Wnt signal channel inhibition activity, particularly including compounds, pharmaceutically acceptable salts, various isotopes, various isomers or various crystal structures thereof having a structure represented by a general formula I (shown in the specification). By the compounds and a composition of the compounds, a Wnt signal channel can be effectively inhibited and diseases related to the Wnt signal channel can be treated or prevented.
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- A catalytic oxidation fragrant boron class compound preparing phenol method (by machine translation)
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The invention discloses a method for catalytic oxidation of phenolic compounds fragrant boron class compound synthesis method, the flux in the solvent in the aqueous solution, under the action of alkali, adding hydrazine hydrate or acid hydrazides catalyst, catalytic oxidation fragrant boron class compound directly for the preparation of phenolic compound. The invention of the method of preparation of the phenol compound, the catalyst is a cheap hydrazine hydrate or hydrazine compound, the oxidizing agent is atmospheric pressure of air or oxygen, the reaction does not need good and activeness metal catalyst, is extensive and stable substrate, substrate-sensitive functional group compatibility good and wide range of application. In the optimized under the reaction conditions, the yield of the target product separation up to 99%. (by machine translation)
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Paragraph 0073; 0097; 0098
(2017/08/08)
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- Exploration of the linkage elements of porcupine antagonists led to potent Wnt signaling pathway inhibitors
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The Wnt signaling pathway is a pivotal developmental pathway. It operates through control of cellular functions such as proliferation, differentiation, migration and polarity. Aberrant Wnt signaling has been implicated in the formation and metastasis of tumors. Porcupine is a component of the Wnt signaling pathway. It is a member of the membrane-bound O-acyltransferase family of proteins. Porcupine catalyzes the palmitoylation of Wnt proteins, a process which is essential to their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from two known porcupine inhibitor classes. The leading compound 62 demonstrated subnanomolar (IC50 0.11 nM) inhibition of Wnt signaling in a paracrine cellular reporter gene assay. Compound 62 also potently inhibited Wnt secretion into culture medium, an indication of direct inhibition of the porcupine protein. Furthermore, compound 62 showed excellent chemical, plasma and liver microsomal stabilities. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors.
- Dong, Yan,Li, Kehuang,Xu, Zhixiang,Ma, Haikuo,Zheng, Jiyue,Hu, Zhilin,He, Sudan,Wu, Yiyuan,Sun, Zhijian,Luo, Lusong,Li, Jiajun,Zhang, Hongjian,Zhang, Xiaohu
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p. 6855 - 6868
(2015/11/11)
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- Discovery of Novel Indazole Derivatives as Highly Potent and Selective Human β3-Adrenergic Receptor Agonists with the Possibility of Having No Cardiovascular Side Effects
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Novel indazole derivatives were prepared and evaluated for their biological activity and cardiovascular safety profile as human β3-adrenergic receptor (AR) agonists. Although the initial hit compound 5 exhibited significant β3-AR agonistic activity (EC50 = 21 nM), it also exhibited agonistic activity at the α1A-AR (EC50 = 219 nM, selectivity: α1A/β3 = 10-fold). The major metabolite of 5, which was an oxidative product at the indazole 3-methyl moiety, gave a clue to a strategy for improvement of the selectivity for β3-AR agonistic activity versus α1A-AR agonistic activity. Thus, modification of the 3-substituent of the indazole moiety effectively improved the selectivity to develop compound 11 with potent β3-AR agonistic activity (EC50 = 13 nM) and high selectivity (α1A/β3 = >769-fold). Compound 11 was also inactive toward β1 and β2-ARs and showed dose dependent β3-AR mediated relaxation of marmoset urinary bladder smooth muscle, while it did not obviously affect heart rate or blood pressure (iv, 3 mg/kg) in anesthetized rats.
- Wada, Yasuhiro,Shirahashi, Hiromitsu,Iwanami, Taisuke,Ogawa, Masami,Nakano, Seiji,Morimoto, Akifumi,Kasahara, Ken-Ichi,Tanaka, Eiichi,Takada, Yoshio,Ohashi, Shigeki,Mori, Mutsuhiro,Shuto, Satoshi
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supporting information
p. 6048 - 6057
(2015/08/24)
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- Aralkylpiperidine (or piperazinecarboxylic) and its derivatives used for treating hypercalcemia schinzopherenia
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PROBLEM TO BE SOLVED: To provide an agent for treating schizophrenia and related neuropsychiatric diseases.SOLUTION: This invention provides an aralkylpiperidine (or piperazine) derivative represented by formula (1), where A ring is a 5-7 membered heterocycle including N, with the heterocycle including a hetero atom arbitrarily selected from O, S, N; X is O, an amino group or a substituted amino group; Z is CH, N or C; Y is O, N or S; n is an integer of 1-5; and R1-R6 are H, a C1-C4 alkyl group or the like.
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Page/Page column 31
(2018/12/01)
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- Unexpected hydrazine hydrate-mediated aerobic oxidation of aryl/ heteroaryl boronic acids to phenols in ambient air
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The expedient and efficient sub-stoichimetric hydrazine hydrate-mediated aerobic hydroxylation of boronic acids that proceeds in poly(ethylene glycol) (PEG-400) has been successfully developed, providing diverse phenols in high yields. And heteroaryl boronic acids are also amenable to this protocol. the Partner Organisations 2014.
- Zhong, Yanzhen,Yuan, Linxin,Huang, Zheng,Gu, Wenchao,Shao, Ye,Han, Wei
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p. 33164 - 33167
(2014/08/18)
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- HETEROARYL COMPOUNDS AND METHODS OF USE THEREOF
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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 neurological disorders, including, but not limited to, e.g., psychosis, schizophrenia, depression, movement disorders, and Parkinson's disease.
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Paragraph 00369; 00370
(2013/12/03)
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- INDAZOLE ANALOGUE
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[Objective] To provide a drug that selectively stimulates the β3-adrenergic receptors, particularly a drug capable of preferentially stimulating the β3-adrenergic receptors over the α1-adrenergic receptors. This drug can be used in the treatment and prevention of diabetes, obesity, hyperlipidemia, depression, cholelithiasis, diseases caused by biliary hyperkinesia, diseases caused by hyperfunction of the gastrointestinal tract, interstitial cystitis, overactive bladder or urinary incontinence, diseases associated with decreased lacrimation, and the like. [Solution] Indazole analogs represented by the general formula (I) or a salt thereof. Drugs that contains these indazole analogs or a salt thereof as the active ingredient.
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Page/Page column 87
(2012/08/14)
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- FUNCTIONALLY SELECTIVE LIGANDS OF DOPAMINE D2 RECEPTORS
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The present invention relates to novel functionally selective ligands of dopamine D2 receptors, including agonists, antagonists, and inverse agonists. The invention further relates to the use of these compounds for treating central nervous system disorders related to D2 receptors.
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Page/Page column 73-74
(2012/01/15)
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- ARALKYL SUBSTITUTED PIPERIDINE OR PIPERAZINE DERIVATIVES AND THEIR USE FOR TREATING SCHIZOPHRENIA
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The present invention discloses an aralkyl substituted piperidine or piperazine derivative and the use of the derivative in preparation of medicaments for treating schizophrenia and correlative psychoneuroses. It is shown by pharmacological tests that the derivative of the present invention has better antischizophrenic effect and less toxicity. Said derivative is a free base or salt of the compound having the following general formula.
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Page/Page column 25-26
(2011/06/10)
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- Toward biophysical probes for the 5-HT3 receptor: Structure-activity relationship study of granisetron derivatives
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This report describes the synthesis and biological characterization of novel granisetron derivatives that are antagonists of the human serotonin (5-HT3A) receptor. Some of these substituted granisetron derivatives showed low nanomolar binding affinity and allowed the identification of positions on the granisetron core that might be used as attachment points for biophysical tags. A BODIPY fluorophore was appended to one such position and specifically bound to 5-HT3A receptors in mammalian cells.
- Vernekar, Sanjeev Kumar V.,Hallaq, Hasan Y.,Clarkson, Guy,Thompson, Andrew J.,Silvestr, Linda,Lummis, Sarah C. R.,Lochner, Martin
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supporting information; experimental part
p. 2324 - 2328
(2010/07/17)
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- INDAZOLE DERIVATIVES
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Compounds represented by the Formula (A-1) and the Formula (1) or salt thereof are provided. The compounds represented by the Formula (A-1) and the Formula (1) or salt thereof have a β3 adrenergic receptor agonist activity, and therefore are useful as an agent for the prevention and treatment of diabetes, obesity, hyperlipidemia, depression, biliary stone, a disorder derived from hyperactivity of biliary tract, a disorder derived from hyperactivity of digestive tract, interstitial cystitis, overactive bladder, urinary incontinence or a disorder derived from decreased tear secretion, etc.
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Page/Page column 51
(2010/06/22)
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- INDAZOLE COMPOUNDS
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Provided are compounds represented by the following formula (A-1) and formula (1), or salts thereof. The compounds of formula (A-1) and formula (1) or salts thereof have 133 adrenergic receptor agonist activity, and thus are useful as therapeutic and prophylactic agent for diabetes mellitus, obesity, hyperlipidemia, depression, diseases caused by gallstones or hypermotility of the biliary tract, diseases caused by hyperactivity of the digestive tract, interstitial cystitis, overactive bladder or urinary incontinence, or as therapeutic and prophylactic agents for diseases concomitant with decreased tears.
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Page/Page column 51
(2010/07/04)
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- FUSED HETEROCYCLIC COMPOUND
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The present invention provides a fused heterocyclic compound having a tyrosine kinase inhibitory action, which is represented by the formula: wherein R1 is a hydrogen atom, a halogen atom, or an optionally substituted group bonded via a carbon atom, a nitrogen atom or an oxygen atom; R2 is a hydrogen atom, or an optionally substituted group bonded via a carbon atom or a sulfur atom, or R1 and R2, or R2 and R3 are optionally bonded to each other to form an optionally substituted ring structure; R3 is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3 is optionally bonded to the carbon atom on ring A to form an optionally substituted ring structure; ring A is an optionally substituted benzene ring; and ring B is (i) an optionally substituted fused ring, or (ii) a pyridine ring having optionally substituted carbamoyl (the pyridine ring is optionally further substituted).
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Page/Page column 75-76
(2009/10/01)
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- Synthesis and structure-activity relationships of a series of substituted 2-(1H-furo[2,3-g]indazol-1-yl)ethylamine derivatives as 5-HT2C receptor agonists
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A series of novel indazole derivatives were synthesized, and their structure-activity relationships examined in order to identify potent and selective 5-HT2C receptor agonists. Among these compounds, (S)-2-(7-ethyl-1H-furo[2,3-g]indazol-1-yl)-1-methylethylamine (YM348) had a good in vitro profile, that is, high agonistic activity to the human 5-HT2C receptor subtype (EC50 = 1.0 nM) and high selectivity over 5-HT2A receptors. This compound was also effective in a rat penile erection model when administered po.
- Shimada, Itsuro,Maeno, Kyoichi,Kazuta, Ken-ichi,Kubota, Hideki,Kimizuka, Tetsuya,Kimura, Yasuharu,Hatanaka, Ken-ichi,Naitou, Yuki,Wanibuchi, Fumikazu,Sakamoto, Shuichi,Tsukamoto, Shin-ichi
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p. 1966 - 1982
(2008/09/21)
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- BENZAZOLE DERIVATIVES, COMPOSITIONS, AND METHODS OF USE AS AURORA KINASE INHIBITORS
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The present invention relates to compounds and methods from the treatment of cancer. The invention provides compounds that inhibit Aurora kinase, pharmaceutical compositions comprising compounds that inhibit Aurora kinase, and methods for the treatment of cancer using the compounds of the presentation invention or pharmaceutical compositions comprising compounds of the present invention.
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Page/Page column 108-109
(2010/11/28)
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- HETEROARYLOXY-SUBSTITUTED PHENYLAMINOPYRIMIDINES AS RHO-KINASE INHIBITORS
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The invention relates to heteroaryloxy-substituted phenylaminopyrimidines, to methods for the production thereof, and to the use of the same for producing medicaments for the treatment and/or prophylaxis of diseases, especially cardiovascular diseases. The inventive compounds inhibit Rho-kinase.
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Page/Page column 60-61
(2010/02/06)
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