778-82-5Relevant academic research and scientific papers
Synthesis and Anticonvulsant Studies of Thiazolidinone and Azetidinone Derivatives from Indole Moiety
Saini, Sachin
, p. 445 - 450 (2019)
2-Amino-5-(3'-indolomethylene)-1, 3, 4 - oxadiazole (3) undergoes facile condensation with various aromatic aldehydes to gave 2-substitiuted arylidenylamino-5-(3'- indolomethylene) - 1, 3, 4 - oxadiazole (4-8). Cyclocondensation of (4-8) with thioglycolic acid and triethylamine yielded 3-[5'-(3- indolomethylene)- 1', 3', 4'- oxadiazol-2'-yl]- 2- (substituted aryl)-4- thiazolidinones (9-13) and 1-[5'-(3- indolomethylene) -1', 3', 4'- oxadiazol - 2'- yl ] -4-(substituted aryl) -2- azetidinones (14-18). The structures of these compounds were established on the basis of analytical and spectral data. The newly synthesised compounds were evaluated for their anticonvulsant activity and acute toxicity.
Diversity-oriented synthesis and antifungal activities of novel pimprinine derivative bearing a 1,3,4-oxadiazole-5-thioether moiety
Song, Zi-Long,Zhu, Yun,Liu, Jing-Rui,Guo, Shu-Ke,Gu, Yu-Cheng,Han, Xinya,Dong, Hong-Qiang,Sun, Qi,Zhang, Wei-Hua,Zhang, Ming-Zhi
, p. 205 - 221 (2020/02/18)
Abstract: Based on the strategy of diversity-oriented synthesis and the structures of natural product pimprinine and streptochlorin, two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties were efficiently synthesized under the optimized reaction conditions. Biological assays conducted at Syngenta showed the designed derivatives displayed an altered pattern of biological activity, of which 5h was identified as the most promising compound with strong activity against Pythium dissimile and also a broad antifungal spectrum in primary screening. Further structural optimization of pimprinine and streptochlorin derivatives is well under way, aiming to discover synthetic analogues with improved antifungal activity. Graphic abstract: Two series of novel pimprinine derivatives containing 1,3,4-oxadiazole-5-thioether moieties wereefficiently synthesized through diversity-oriented synthesis strategy under the optimizedconditions. Biological assays showed the designed derivatives exhibited potential activity.[Figure not available: see fulltext.].
Remarkably Efficient Iridium Catalysts for Directed C(sp2)-H and C(sp3)-H Borylation of Diverse Classes of Substrates
Chattopadhyay, Buddhadeb,Hassan, Mirja Md Mahamudul,Hoque, Md Emdadul
supporting information, p. 5022 - 5037 (2021/05/04)
Here we describe the discovery of a new class of C-H borylation catalysts and their use for regioselective C-H borylation of aromatic, heteroaromatic, and aliphatic systems. The new catalysts have Ir-C(thienyl) or Ir-C(furyl) anionic ligands instead of the diamine-type neutral chelating ligands used in the standard C-H borylation conditions. It is reported that the employment of these newly discovered catalysts show excellent reactivity and ortho-selectivity for diverse classes of aromatic substrates with high isolated yields. Moreover, the catalysts proved to be efficient for a wide number of aliphatic substrates for selective C(sp3)-H bond borylations. Heterocyclic molecules are selectively borylated using the inherently elevated reactivity of the C-H bonds. A number of late-stage C-H functionalization have been described using the same catalysts. Furthermore, we show that one of the catalysts could be used even in open air for the C(sp2)-H and C(sp3)-H borylations enabling the method more general. Preliminary mechanistic studies suggest that the active catalytic intermediate is the Ir(bis)boryl complex, and the attached ligand acts as bidentate ligand. Collectively, this study underlines the discovery of new class of C-H borylation catalysts that should find wide application in the context of C-H functionalization chemistry.
A new CDK2 inhibitor with 3-hydrazonoindolin-2-one scaffold endowed with anti-breast cancer activity: Design, synthesis, biological evaluation, and in silico insights
Al-Sanea, Mohammad M.,Obaidullah, Ahmad J.,Shaker, Mohamed E.,Chilingaryan, Garri,Alanazi, Mohammed M.,Alsaif, Nawaf A.,Alkahtani, Hamad M.,Alsubaie, Sultan A.,Abdelgawad, Mohamed A.
, (2021/02/27)
Background: Cyclin-dependent kinases (CDKs) regulate mammalian cell cycle progression and RNA transcription. Based on the structural analysis of previously reported CDK2 inhibitors, a new compound with 3-hydrazonoindolin-2-one scaffold (HI 5) was well designed, synthesized, and biologically evaluated as a promising anti-breast cancer hit compound. Methods: The potential anti-cancerous effect of HI 5 was evaluated using cytotoxicity assay, flow cytometric analysis of apoptosis and cell cycle distribution, ELISA immunoassay, in vitro CDK2/cyclin A2 activity, and molecular operating environment (MOE) virtual docking studies. Results: The results revealed that HI 5 exhibits pronounced CDK2 inhibitory activity and cytotoxicity in human breast cancer MCF-7 cell line. The cytotoxicity of HI 5 was found to be intrinsically mediated apoptosis, which in turn, is associated with low Bcl-2 expression and high activation of caspase 3 and p53. Besides, HI 5 blocked the proliferation of the MCF-7 cell line and arrested the cell cycle at the G2/M phase. The docking studies did not confirm which one of geometric isomers (syn and anti) is responsible for binding affinity and intrinsic activity of HI 5. However, the molecular dynamic studies have confirmed that the syn-isomer has more favorable binding interaction and thus is responsible for CDK2 inhibitory activity. Discussion: These findings displayed a substantial basis of synthesizing further derivatives based on the 3-hydrazonoindolin-2-one scaffold for favorable targeting of breast cancer.
Enantioselective Desymmetrization of 2-Aryl-1,3-propanediols by Direct O-Alkylation with a Rationally Designed Chiral Hemiboronic Acid Catalyst That Mitigates Substrate Conformational Poisoning
Estrada, Carl D.,Ang, Hwee Ting,Vetter, Kim-Marie,Ponich, Ashley A.,Hall, Dennis G.
supporting information, (2021/04/07)
Enantioselective desymmetrization by direct monofunctionalization of prochiral diols is a powerful strategy to prepare valuable synthetic intermediates in high optical purity. Boron acids can activate diols toward nucleophilic additions; however, the design of stable chiral catalysts remains a challenge and highlights the need to identify new chemotypes for this purpose. Herein, the discovery and optimization of a bench-stable chiral 9-hydroxy-9,10-boroxarophenanthrene catalyst is described and applied in the highly enantioselective desymmetrization of 2-aryl-1,3-diols using benzylic electrophiles under operationally simple, ambient conditions. Nucleophilic activation and discrimination of the enantiotopic hydroxy groups on the diol substrate occurs via a defined chairlike six-membered anionic complex with the hemiboronic heterocycle. The optimal binaphthyl-based catalyst 1g features a large aryloxytrityl group to effectively shield one of the two prochiral hydroxy groups on the diol complex, whereas a strategically placed "methyl blocker"on the boroxarophenanthrene unit mitigates the deleterious effect of a competing conformation of the complexed diol that compromised the overall efficiency of the desymmetrization process. This methodology affords monoalkylated products in enantiomeric ratios equal or over 95:5 for a wide range of 1,3-propanediols with various 2-aryl/heteroaryl groups.
Investigation of indole functionalized pyrazoles and oxadiazoles as anti-inflammatory agents: Synthesis, in-vivo, in-vitro and in-silico analysis
Kalra, Sourav,Kumar, Bhupinder,Kumar, Devendra,Kumar, Ravi Ranjan,Pathania, Shelly,Singh, Pankaj Kumar
, (2021/06/16)
There are several potential side and adverse effects are found to be associated with the anti-inflammatory drugs in clinical practice. The long-term use of these clinical agents highly unsafe. It encouraged the development of novel heterocyclic compounds with potential anti-inflammatory activity and low to no toxicity. In present investigation, a total of 12 indole functionalized pyrazole and oxadiazole derivatives were designed, synthesized and evaluated for the in-vivo anti-inflammatory and analgesic potential. These compounds displayed comparable anti-inflammatory and analgesic potential to the reference drugs. Finally, molecular docking analysis was performed considering different anti-inflammatory targets to determine the mechanistic target of the designed molecules. Detailed analysis suggested that the molecules inhibit COX-2, preferably over other anti-inflammatory targets. The results suggested that two compounds (15c and 15f) were found promising candidates for the development of novel anti-inflammatory agents.
Synthesis, Pharmacological Evaluation and Molecular Docking Studies of N-[2-(1H-indol-3-yl)Acetyl]Arylsulfonohydrazides
Abbasi, M. A.,Ahmad, I.,Ashraf, M.,Aziz-ur-Rehman,Fatima, Hina,Khan, F. A.,Lodhi, M. A.,Qurat-ul-Ain,Rubab, K.,Shah, S. A. A.,Shahid, M.,Siddiqui, S. Z.
, p. 665 - 678 (2021/10/30)
Synthesis of heterocyclic compounds encompassing multiple functionalities and their biological screening is the most adapted strategy in the world for pharmacological evaluation of future drug candidates. The undertaken research was initiated by esterification 2-(1H-indol-3-yl)acetic acid (1) with catalytic amount of sulfuric acid in ethanol to ethyl 2-(1H-indol-3-yl)acetate (2), which was then reacted with hydrazine hydrate in methanol to achieve 2-(1H-indol-3-yl)acetohydrazide (3). The corresponding hydrazide 3 was reacted with a variety of arylsulfonyl chlorides (4a-j) in sodium carbonate solution (pH 9-10) to afford N-[2-(1H-indol-3-yl)acetyl]arylsulfonohydrazides (5a-j). The structural characterization of synthesized compounds was done by 1H-NMR, 13C-NMR, IR and EI-MS spectral data. Moreover, these derivatives were evaluated for anti-bacterial potentials along with their % age hemolytic and enzyme inhibitory activities. It was found that compounds 5a, 5b, 5d and 5h revealed good anti-bacterial against all the bacterial strains used in this study, while 5d, 5g and 5h exhibited good enzyme inhibition potentials against BChE which were close to the reference standard eserine. These compounds also revealed low values of % hemolytic activity. Results of computational docking were also found in agreement with the enzyme inhibition data.
Discovery, synthesis and biological characterization of a series of: N -(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1 H -pyrazol-5-yl)acetamide ethers as novel GIRK1/2 potassium channel activators
Alnouti, Yazen,Aretz, Christopher D.,Chhonker, Yashpal S.,Dhuria, Nikilesh V.,Du, Yu,Gautam, Nagsen,Hopkins, Corey R.,Kumar, Sushil,Lesiak, Lauren,Sharma, Swagat,Weaver, C. David
supporting information, p. 1366 - 1373 (2021/09/28)
The present study describes the discovery and characterization of a series of N-(1-(1,1-dioxidotetrahydrothiophen-3-yl)-3-methyl-1H-pyrazol-5-yl)acetamide ethers as G protein-gated inwardly-rectifying potassium (GIRK) channel activators. From our previous lead optimization efforts, we have identified a new ether-based scaffold and paired this with a novel sulfone-based head group to identify a potent and selective GIRK1/2 activator. In addition, we evaluated the compounds in tier 1 DMPK assays and have identified compounds that display nanomolar potency as GIRK1/2 activators with improved metabolic stability over the prototypical urea-based compounds. This journal is
Fe-catalyzed Fukuyama-type indole synthesis triggered by hydrogen atom transfer
Huang, Hanmin,Yu, Min,Zhang, Tianze
, p. 10501 - 10505 (2021/08/20)
Fe, Co, and Mn hydride-initiated radical olefin additions have enjoyed great success in modern synthesis, yet the extension of other hydrogen radicalophiles instead of olefins remains largely elusive. Herein, we report an efficient Fe-catalyzed intramolec
SUBSTITUTED TETRAHYDROPYRANOINDOLES, DERIVATIVES THEREOF, AND THEIR METHODS OF SYNTHESIS AND USE
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Paragraph 0146; 0147; 0175; 0176, (2021/01/25)
Disclosed herein are tetrahydropyranoindole compounds and derivatives thereof, as well as their methods of synthesis and use. The disclosed compounds may be synthesized by methods that utilize a cooperative hydrogen bond donor/Br?nsted acid system. The disclosed compounds may be useful for treating a disease, disorder, or a symptom thereof in a subject in need thereof, such as pain, swelling, and joint stiffness. The disclosed compounds also may be useful for treating cell proliferative diseases and disorders such as cancer.
