2945-03-1Relevant articles and documents
Synthesis of Novel Bi-Heterocycles as Valuable Anti-Diabetic Agents: 2-({5-((2-Amino-1,3-Thiazol-4-yl)methyl)-1,3,4-Oxadiazol-2-yl}sulfanyl)-N-(Substituted)acetamides
Aziz-ur-Rehman,Khan, Farman Ali,Lodhi, Muhammad Arif,Mirza, Bushra,Muhammad, Athar Abbasi,Ramzan, Muhammad Shahid,Shah, Syed Adnan Ali,Siddiqui, Sabahat Zahra
, p. 590 - 598 (2020)
Abstract: The synthesis of a new series of S-substituted acetamides derivatives of 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol were synthesized and evaluated for enzyme inhibition study along with cytotoxic behavior. Ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate was converted to corresponding acid hydrazide by hydrazine hydrate in ethanol. The reflux of acid hydrazide with carbon disulfide resulted to 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol. Different electrophiles were synthesized by the reaction of respective anilines (one in each reaction) and 2-bromoacetylbromide in an aqueous medium. The targeted bi-heterocyclic compounds were synthesized by stirring nucleophilic 5-[(2-amino-1,3-thiazol-4-yl)methyl]-1,3,4-oxadiazol-2-thiol with different acetamides electrophiles (one after another), in DMF using LiH as base and activator. The proposed structures of newly synthesized compounds were deduced by spectroscopic techniques such as 1H NMR, 13C NMR, EI MS and elemental analysis. These novel bi-heterocycles were tested for their anti-diabetic potential via the in vitro inhibition of α-glucosidase enzyme. The in silico study of these molecules was also coherent with their enzyme inhibition data. Furthermore, these molecules were analyzed for their cytotoxic behavior against brine shrimps. It was inferred from the results that most of them exhibited very potent inhibitory potential against the studied enzyme and can be utilized as valuable anti-diabetic agent.
Gold-Catalyzed Unexpected Ring Transformation of Pyrimidodiazepine Derivatives
Koo, Jaeyoung,Kim, Jonghoon,Park, Seung Bum
, p. 344 - 347 (2017)
Pyrimidodiazepine derivatives underwent an unexpected gold-catalyzed retro-Mannich-type carbon-carbon bond cleavage and intramolecular nucleophilic cyclization. The pyrimidodiazepines bearing an alkyne moiety showed novel orthogonal reactivity in the presence of a gold catalyst, as opposed to the alkynophilicity that is commonly observed with gold catalysts. The ring transformation reaction of pyrimidodiazepines probably proceeds through an acyclic iminium intermediate. The potential of this synthetic method for the skeletal diversification of pyrimidine-containing macrocycles was also demonstrated.
Synthesis and antiviral activity of a series of novel quinoline derivatives as anti-RSV or anti-IAV agents
Wang, Minghua,Zhang, Guoning,Zhao, Jianyuan,Cheng, Ningning,Wang, Yujia,Fu, Yuanhui,Zheng, Yanpeng,Wang, Juxian,Zhu, Mei,Cen, Shan,He, Jinsheng,Wang, Yucheng
, (2021)
We report herein the synthesis of a series of novel quinoline derivatives, based on the lead compound 1a, identified from a rRSV-mGFP high-throughput screening assay. Our results revealed that target compounds 1b, 1g-h, 1af and 1ah (IC50 = 3.10–6.93 μM) had good in vitro activity against RSV, which were better than 1a and ribavirin. In addition, we found that compound 1g displayed the lower cytotoxicity (CC50: 2490.33 μM) and the highest selective index (SI = 673.06), suggesting its promising potential as a candidate for further development. On the other hand, compounds 1a, 1m, 1v, 1ad-1af and 1ah-1ai (IC50s: 1.87–14.28 μM) were more active against IAV than or comparable to ribavirin (IC50: 15.36 ± 0.93 μM). Particularly, the most active compound 1ae (IC50: 1.87 ± 0.58 μM) was found to be 8.2-fold more potent than the reference drug, which could inhibit the virus transcription and replication cycle at an early stage.
BENZYLAMIDE DERIVATIVES AS INHIBITORS OF TRANSFORMING GROWTH FACTOR-BETA RECEPTOR I/ALK5
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Page/Page column 33, (2021/06/04)
The present invention relates to novel benzylamide derivatives of formula (I) to processes for the preparation of said compounds; to pharmaceutical compositions comprising said compounds and to said compounds for use in the treatment of pathological conditions or diseases that can improve by inhibition of transforming growth factor-β receptor I (TGFβRI)/ALK5, such as diseases and disorders associated to fibrotic conditions of gastrointestinal system, skin and eyes, to methods for the treatment and/or prevention of said diseases or pathological conditions and to combinations comprising said compounds and further comprising therapeutically effective amounts of other therapeutic agents useful for the treatment of said diseases or pathological conditions.
Synthesis and in Vitro Evaluation of Novel 5-Nitroindole Derivatives as c-Myc G-Quadruplex Binders with Anticancer Activity
Nimbarte, Vijaykumar D.,Wirmer-Bartoschek, Julia,Gande, Santosh L.,Alshamleh, Islam,Seibert, Marcel,Nasiri, Hamid Reza,Schnütgen, Frank,Serve, Hubert,Schwalbe, Harald
supporting information, p. 1667 - 1679 (2021/03/24)
Lead-optimization strategies for compounds targeting c-Myc G-quadruplex (G4) DNA are being pursued to develop anticancer drugs. Here, we investigate the structure-activity- relationship (SAR) of a newly synthesized series of molecules based on the pyrrolidine-substituted 5-nitro indole scaffold to target G4 DNA. Our synthesized series allows modulation of flexible elements with a structurally preserved scaffold. Biological and biophysical analyses illustrate that substituted 5-nitroindole scaffolds bind to the c-Myc promoter G-quadruplex. These compounds downregulate c-Myc expression and induce cell-cycle arrest in the sub-G1/G1 phase in cancer cells. They further increase the concentration of intracellular reactive oxygen species. NMR spectra show that three of the newly synthesized compounds interact with the terminal G-quartets (5′- and 3′-ends) in a 2 : 1 stoichiometry.
