231295-53-7Relevant academic research and scientific papers
N-(PHENYL)-INDOLE-3-SULFONAMIDE DERIVATIVES AND RELATED COMPOUNDS AS GPR17 MODULATORS FOR TREATING CNS DISORDERS SUCH AS MULTIPLE SCLEROSIS
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Page/Page column 62, (2021/01/22)
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
PYRIDINYL AND PYRAZINYL-(AZA)INDOLSULFONAMIDES
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Page/Page column 92-94, (2020/01/11)
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.
(AZA)INDOLE-, BENZOTHIOPHENE-, AND BENZOFURAN-3-SULFONAMIDES
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Page/Page column 259; 260, (2018/07/29)
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.
Development of indole sulfonamides as cannabinoid receptor negative allosteric modulators
Greig, Iain R.,Baillie, Gemma L.,Abdelrahman, Mostafa,Trembleau, Laurent,Ross, Ruth A.
, p. 4403 - 4407 (2016/08/25)
Existing CB1 negative allosteric modulators (NAMs) fall into a limited range of structural classes. In spite of the theoretical potential of CB1 NAMs, published in vivo studies have generally not been able to demonstrate the expected therapeutically-relevant CB1-mediated effects. Thus, a greater range of molecular tools are required to allow definitive elucidation of the effects of CB1 allosteric modulation. In this study, we show a novel series of indole sulfonamides. Compounds 5e and 6c (ABD1075) had potencies of 4 and 3?nM respectively, and showed good oral exposure and CNS penetration, making them highly versatile tools for investigating the therapeutic potential of allosteric modulation of the cannabinoid system.
Design, synthesis and structure-activity relationship studies of novel and diverse cyclooxygenase-2 inhibitors as anti-inflammatory drugs
Hayashi, Shigeo,Ueno, Naomi,Murase, Akio,Takada, Junji
, p. 846 - 867 (2015/02/19)
Because of the pivotal role of cyclooxygenase (COX) in the inflammatory processes, non-steroidal anti-inflammatory drugs (NSAIDs) that suppress COX activities have been used clinically for the treatment of inflammatory diseases/syndromes; however, traditional NSAIDs exhibit serious side-effects such as gastrointestinal damage and hyper sensitivity owing to their COX-1 inhibition. Also, COX-2 inhibition-derived suppressive or preventive effects against initiation/proliferation/invasion/motility/recurrence/metastasis of various cancers/tumours such as colon, gastric, skin, lung, liver, pancreas, breast, prostate, cervical and ovarian cancers are significant. In this study, design, synthesis and structure-activity relationship (SAR) of various novel {2-[(2-, 3- and/or 4-substituted)-benzoyl, (bicyclic heterocycloalkanophenyl)carbonyl or cycloalkanecarbonyl]-(5- or 6-substituted)-1H-indol-3-yl}acetic acid analogues were investigated to seek and identify various chemotypes of potent and selective COX-2 inhibitors for the treatment of inflammatory diseases, resulting in the discovery of orally potent agents in the peripheral-inflammation model rats. The SARs and physicochemical properties for the analogues are described as significant findings. For graphical abstract: see Supplementary Material. (www.informahealthcare.com/enz)
N- (ARYLALKYL) - 1H- INDOLE- 2 - SULFONIC ACID AMIDE COMPOUNDS AND THEIR THERAPEUTIC USE AS CANNABINOID ALLOSTERIC MODULATORS
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Page/Page column 140, (2012/09/21)
The present invention pertains generally to the field of therapeutic compounds. More specifically the present invention pertains to certain /V-(arylalkyl)-1 H-indole- 2-sulfonic acid amide compounds that, inter alia, inhibit cannabinoid receptor signalling. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit cannabinoid receptor signalling; to treat disorders that are ameliorated by the inhibition of cannabinoid receptor signalling; to treat metabolic syndrome, type-2 diabetes, dyslipidaemia, obesity, eating disorders, cardiovascular diseases and disorders, and other conditions as described herein.
Regiocontrolled aerobic oxidative coupling of indoles and benzene using Pd catalysts with 4,5-diazafluorene ligands
Campbell, Alison N.,Meyer, Eric B.,Stahl, Shannon S.
supporting information; experimental part, p. 10257 - 10259 (2011/10/19)
Palladium-catalyzed aerobic oxidative cross-couplings of indoles and benzene have been achieved by using 4,5-diazafluorene derivatives as ancillary ligands. Proper choice of the neutral and anionic ligands enables control over the reaction regioselectivit
Synthesis and antiproliferative activity of novel 2-aryl-4-benzoyl- imidazole derivatives targeting tubulin polymerization
Chen, Jianjun,Li, Chien-Ming,Wang, Jin,Ahn, Sunjoo,Wang, Zhao,Lu, Yan,Dalton, James T.,Miller, Duane D.,Li, Wei
experimental part, p. 4782 - 4795 (2011/09/20)
We previously reported the discovery of 2-aryl-4-benzoyl-imidazoles (ABI-I) as potent antiproliferative agents for melanoma. To further understand the structural requirements for the potency of ABI analogs, gain insight in the structure-activity relationships (SAR), and investigate metabolic stability for these compounds, we report extensive SAR studies on the ABI-I scaffold. Compared with the previous set of ABI-I analogs, the newly synthesized ABI-II analogs have lower potency in general, but some of the new analogs have comparable potency to the most active compounds in the previous set when tested in two melanoma and four prostate cancer cell lines. These SAR studies indicated that the antiproliferative activity was very sensitive to subtle changes in the ligand. Tested compounds 3ab and 8a are equally active against highly paclitaxel resistant cancer cell lines and their parental cell lines, indicating that drugs developed based on ABI-I analogs may have therapeutic advantages over paclitaxel in treating resistant tumors. Metabolic stability studies of compound 3ab revealed that N-methyl imidazole failed to extend stability as literature reported because de-methylation was found as the major metabolic pathway in rat and mouse liver microsomes. However, this sheds light on the possibility for many modifications on imidazole ring for further lead optimization since the modification on imidazole, such as compound 3ab, did not impact the potency.
Efficient sulfonation of 1-phenylsulfonyl-1H-pyrroles and 1-phenylsulfonyl-1H-indoles using chlorosulfonic acid in acetonitrile
Janosik, Tomasz,Shirani, Hamid,Wahlstr?m, Niklas,Malky, Ilham,Stensland, Birgitta,Bergman, Jan
, p. 1699 - 1707 (2007/10/03)
The sulfonation of various 1-phenylsulfonyl-1H-pyrroles and 1-phenylsulfonyl-1H-indoles using chlorosulfonic acid in acetonitrile has been studied, leading to the development of a clean and operationally simple protocol allowing direct synthesis of the corresponding 1-phenylsulfonyl-1H-pyrrole-3- sulfonyl chlorides and 1-phenylsulfonyl-1H-indole-3-sulfonyl chlorides, respectively, both of which may be easily converted to various sulfonamide derivatives by treatment with nitrogen nucleophiles. Efficient and selective removal of the phenylsulfonyl- or tosyl groups in the sulfonamide series may be achieved under mild conditions.
Novel bis(1H-indol-2-yl)methanones as potent inhibitors of FLT3 and platelet-derived growth factor receptor tyrosine kinase
Mahboobi, Siavosh,Uecker, Andrea,Sellmer, Andreas,Cénac, Christophe,H?cher, Heymo,Pongratz, Herwig,Eichhorn, Emerich,Hufsky, Harald,Trümpler, Antje,Sicker, Marit,Heidel, Florian,Fischer, Thomas,Stocking, Carol,Elz, Sigurd,B?hmer, Frank-D.,Dove, Stefan
, p. 3101 - 3115 (2007/10/03)
FLT3 receptor tyrosine kinase is aberrantly active in many cases of acute myeloid leukemia (AML). Recently, bis(1H-indol-2-yl)methanones were found to inhibit FLT3 and PDGFR kinases. To optimize FLT3 activity and selectivity, 35 novel derivatives were synthesized and tested for inhibition of FLT3 and PDGFR autophosphorylation. The most potent FLT3 inhibitors 98 and 102 show IC 50 values of 0.06 and 0.04 μM, respectively, and 1 order of magnitude lower PDGFR inhibiting activity. The derivatives 76 and 82 are 20- to 40-fold PDGFR selective. Docking at the recent FLT3 structure suggests a bidentate binding mode with the backbone of Cys-694. Activity and selectivity can be related to interactions of one indole moiety with a Hydrophobic pocket including Phe-691, the only different binding site residue (PDGFR Thr-681). Compound 102 inhibited the proliferation of 32D cells expressing wildtype FLT3 or FLT3-ITD similarly as FLT3 autophosphorylation, and induced apoptosis in primary AML patient blasts.
