- Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors
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Multiple lines of evidence have indicated that pyruvate kinase M2 (PKM2) is upregulated in most cancer cells and it is increasingly recognized as a potential therapeutic target in oncology. In a continuation of our discovery of lead compound 5 and SAR study, the 7-azaindole moiety in compound 5 was systematically optimized. The results showed that compound 6f, which has a difluoroethyl substitution on the 7-azaindole ring, exhibited high PKM2 activation potency and anti-proliferation activities on A375 cell lines. In a xenograft mouse model, oral administration of compound 6f led to significant tumor regression without obvious toxicity. Further mechanistic studies revealed that 6f could influence the translocation of PKM2 into nucleus, as well as induction of apoptosis and autophagy of A375 cells. More importantly, compound 6f significantly inhibited migration of A375 cells in a concentration-dependent manner. Collectively, 6f may serve as a lead compound in the development of potent PKM2 activators for cancer therapy.
- Liu, Bin,Yuan, Xia,Xu, Bo,Zhang, Han,Li, Ridong,Wang, Xin,Ge, Zemei,Li, Runtao
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- COMPOUNDS FOR USING IN IMAGING AND PARTICULARLY FOR THE DIAGNOSIS OF NEURODEGENERATIVE DISEASES
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The invention relates to compounds of formula (II) for using in imaging and particularly for the diagnosis of neurodegenerative diseases
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Paragraph 0594; 0597
(2019/07/23)
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- Preparation method of drug composition for treating febrile convulsion in children
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The invention relates to a preparation method of a drug composition for treating febrile convulsion in children. The method comprises a route as shown in the specification. A treatment mechanism of the drug of the invention is to prolong the convulsion latency of a febrile convulsion patient, shorten the convulsion duration, relieve the convulsion seriousness, inhibit apoptosis of hippocampal neurons, regulate the levels of GABA and Glu, relieve the cerebral injury of febrile convulsion patient and finally achieve the purpose of treating the febrile convulsion.
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- Synthetic method of 6-chloro-7-azaindole
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The invention discloses a synthetic method of 6-chloro-7-azaindole, belonging to the field of chemical synthesis. 7-azaindole is taken as a raw material, and the 6-chloro-7-azaindole is synthesized by three actions of N-oxidation, chlorination and hydrolysis. The process route is optimized, and the yield is improved by 70% or more, and is improved by 7% compared with the prior art. The improved synthetic route is simple to operate and feasible, the economic benefits are effectively improved, and large-scale industrial promotion is facilitated.
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Paragraph 0046; 0047; 0048
(2017/01/02)
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- ARYLOXYACETYLINDOLES AND ANALOGS AS ANTIBIOTIC TOLERANCE INHIBITORS
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The disclosure provides compounds and pharmaceutical compositions of aryloxyacetylindoles compounds and analogs useful for treating chronic and acute bacterial infections. Certain of the compounds are compounds of general Formula (I) (I) or a pharmaceutically acceptable salt or prodrug thereof. Certain compounds of this disclosure are MvfR inhibitors. MvfR inhibitors reduce the formation of antibiotic tolerant bacterial strains and are useful for treating Gram-negative bacterial infections and reducing the virulence of Pseudomonas aeruginosa. Methods of treating bacterial infections in a subject, including Pseudomonas aeruginosa infections, are also provided by the disclosure.
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Paragraph 0447
(2016/08/10)
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- ANTICANCER AGENT
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An anticancer agent comprising a compound represented by the formula (I) [R1 represents hydrogen atom, hydroxyl group, a C1-6alkoxy group and the like; R2 and R3 represents hydrogen atom, a halogen atom, a C1-6alkyl group and the like; R4 represents hydrogen atom, a C1-6alkyl group, a C1-6alkylsulfonyl group and the like; R5 represents hydrogen atom or a substituent; .... represents a single bond or a double bond; R6 and R7 represents hydrogen atom, a C1-6alkyl group and the like; R8 represents hydrogen atom, a C1-6alkyl group and the like; A represents -O-, -S-, or - CH2-; D represents -C= or -N=; X represents methylene group, -O-, or -CO-; Q represents -N= or -C(R8)=; and Y represents a heterocyclic group or amino group], which shows a superior inhibitory activity against pim-1 kinase.
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Paragraph 0278
(2013/03/26)
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- NEW CRTH2 ANTAGONISTS
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The present invention relates to compounds of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by CRTh2 antagonist activity.
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- New CRTh2 antagonists
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The present invention relates to compounds of formula (I), to the process for preparing such compounds and to their use in the treatment of a pathological condition or disease susceptible to amelioration by CRTh2 antagonist activity.
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Paragraph 0438-0441
(2013/03/26)
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- Scaffold-hopping strategy: Synthesis and biological evaluation of 5,6-fused bicyclic heteroaromatics to identify orally bioavailable anticancer agents
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Utilizing scaffold-hopping drug-design strategy, we sought to identify a backup drug candidate for BPR0L075 (1), an indole-based anticancer agent. For this purpose, 5,6-fused bicyclic heteroaromatic scaffolds were designed and synthesized through shufflin
- Tung, Yen-Shih,Coumar, Mohane Selvaraj,Wu, Yu-Shan,Shiao, Hui-Yi,Chang, Jang-Yang,Liou, Jing-Ping,Shukla, Paritosh,Chang, Chun-Wei,Chang, Chi-Yen,Kuo, Ching-Chuan,Yeh, Teng-Kuang,Lin, Chin-Yu,Wu, Jian-Sung,Wu, Su-Ying,Liao, Chun-Chen,Hsieh, Hsing-Pang
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scheme or table
p. 3076 - 3080
(2011/06/25)
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- Discovery and optimization of indoles and 7-azaindoles as Rho kinase (ROCK) inhibitors (part-I)
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Rho kinase (ROCK) inhibitors are potential therapeutic agents to treat disorders such as hypertension, multiple sclerosis, cancers, and glaucoma. Here, we disclose the synthesis, optimization, biological evaluation of potent indole and 7-azaindole based ROCK inhibitors that have high potency on ROCK (IC 50 = 1 nM) with 740-fold selectivity over PKA (47). Moreover, 47 showed very good DMPK properties making it a good candidate for further development. Finally, docking studies with a homology model of ROCK-II were performed to rationalize the binding mode of these compounds and showed the compounds bound in both orientations to take advantage to H-bonds with Lys-121 of ROCK-II.
- Chowdhury, Sarwat,Sessions, E. Hampton,Pocas, Jennifer R.,Grant, Wayne,Schr?ter, Thomas,Lin, Li,Ruiz, Claudia,Cameron, Michael D.,Schürer, Stephan,Lograsso, Philip,Bannister, Thomas D.,Feng, Yangbo
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scheme or table
p. 7107 - 7112
(2012/01/05)
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- 4-(Heteroaryl-methyl and substituted heteroaryl-methyl)-imidazole-2-thiones acting as alpha2 adrenergic agonists
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Compounds of Formula 1 where the variables have the meaning defined in the specification are agonists of alpha2 adrenergic receptors. Several compounds of the disclosure are specific or selective to alpha2B and/or alpha2C adrenergic receptors in preference over alpha2A adrenergic receptors. Additionally some of the claimed compounds have no or only minimal cardivascular and/or sedatory activity. The compounds of Formula 1 are useful as medicaments in mammals, including humans, for treatment of diseases and or alleviations of conditions which are responsive to treatment by agonists of alpha2 adrenergic receptors. Compounds of Formula 1 which have no significant cardiovascular and/or sedatory activity are useful for treating pain and other conditions with minimal side effects.
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Page/Page column 18-19
(2010/10/20)
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- COMPOSITIONS USEFUL AS INHIBITORS OF PROTEIN KINASES
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The present invention relates to compounds useful of inhibitors of protein kinases. The invention also provides pharmaceutically acceptable compositions comprising said compounds and methods of using the compositions in the treatment of various disease, conditions, or disorders.
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Page/Page column 175
(2010/02/11)
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- Regioselective functionalization of 1H-pyrrolo[2,3-b]pyridine via its N-oxide
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Selective functionalization of 1H-pyrrolo[2,3-b]pyridine (7-azaindole) at the 6-position was achieved by Reissert-Henze type reaction. Thus, halogeno (Cl, Br, I), cyano and thiocyanato groups were directly introduced to the pyridine ring of 7-azaindole.
- Minakata,Komatsu,Ohshiro
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p. 661 - 663
(2007/10/02)
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