- N-(PHENYL)-INDOLE-3-SULFONAMIDE DERIVATIVES AND RELATED COMPOUNDS AS GPR17 MODULATORS FOR TREATING CNS DISORDERS SUCH AS MULTIPLE SCLEROSIS
-
Disclosed are N-(phenyl)-lH-indole-3-sulfonamide and N-(phenyl) -1 H-pyrrolo[2,3-b]pyridine-3-sulfonamide derivatives of formula I substituted at the 1- and 6-positions of the 1H-indole or 1H-pyrrolo[2,3-b]pyridine moiety, as well as structurally related
- -
-
Page/Page column 63
(2021/01/22)
-
- Synthesis of novel 7-azaindole derivatives containing pyridin-3-ylmethyl dithiocarbamate moiety as potent PKM2 activators and PKM2 nucleus translocation inhibitors
-
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
-
-
- PYRIDINYL AND PYRAZINYL-(AZA)INDOLSULFONAMIDES
-
The present invention relates to pyridinyl and pyrazinyl-(aza)indolsulfonamides having GPR17 modulator activity. The compounds have utility in the treatment of a variety of GPR17-associated disorders.
- -
-
Page/Page column 92; 94-95
(2020/01/11)
-
- (AZA)INDOLE-, BENZOTHIOPHENE-, AND BENZOFURAN-3-SULFONAMIDES
-
Disclosed are sulfonamide compounds with GPR17 modulating properties, which are useful for treating or preventing a variety of CNS and other diseases, in particular for preventing and treating myelinating diseases or disorders.
- -
-
Page/Page column 260; 261
(2018/07/29)
-
- Scaffold-hopping strategy: Synthesis and biological evaluation of 5,6-fused bicyclic heteroaromatics to identify orally bioavailable anticancer agents
-
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
-
p. 3076 - 3080
(2011/06/25)
-
- 7-Azaindole derivatives as potential partial nicotinic agonists
-
We have investigated a series of 7-azaindoles as potential partial agonists of the α4β2 nicotinic acetylcholine receptor (nAChR). Three series of 7-azaindole derivatives have been synthesized and evaluated for rat brain neuronal nicotinic receptor affinity and functional activity. Compound (+)-51 exhibited the most potent nAChR binding (Ki = 10 nM). Compound 30A demonstrated both moderate binding affinity and partial agonist potency, thus representing a promising lead for the indications of cognition and smoking cessation.
- Stoit, Axel R.,den Hartog, Arnold P.,Mons, Harry,van Schaik, Sjoerd,Barkhuijsen, Nynke,Stroomer, Cees,Coolen, Hein K.A.C.,Reinders, Jan Hendrik,Adolfs, Tiny J.P.,van der Neut, Martina,Keizer, Hiskias,Kruse, Chris G.
-
p. 188 - 193
(2008/12/23)
-
- AZAINDOLE DERIVATIVES WITH A COMBINATION OF PARTIAL NICOTINIC ACETYL-CHOLINE RECEPTOR AGONISM AND DOPAMINE REUPTAKE INHIBITION
-
Azaindole derivatives of formula (I): wherein the symbols have the meanings given in the specification, are described. These compounds have a combination of partial nicotinic acetylcholine receptor agonism and dopamine reuptake inhibition. The invention also relates to pharmaceutical compositions containing these compounds, to methods for preparing them, methods for preparing novel intermediates useful for their synthesis, methods for preparing compositions, and uses of such compounds and compositions, for example, their use in administering them to patients to achieve a therapeutic effect in disorders in which nicotinic receptors and/or dopamine transporters are involved, or that can be treated via manipulation of those receptors
- -
-
Page/Page column 21
(2008/06/13)
-
- Anti-tumor compounds
-
Compounds of the following formula: wherein A, D, Q, T, U, V, W, X, Y, Z, R1, and ---- are as defined herein. This invention also relates to a method of inhibiting tubulin polymerization, or treating cancer or an angiogenesis-related disorder w
- -
-
Page/Page column 11
(2008/06/13)
-
