176450-08-1Relevant academic research and scientific papers
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
Molecular docking and synthesis of caffeic acid analogous and its anti-inflammatory, analgesic and ulcerogenic studies
Al-Ostoot, Fares Hezam,Ara Khanum, Shaukath,Grisha, S.,Mohammed, Yasser Hussein Eissa,Vivek, H. K.,Zabiulla
, (2020/12/25)
A series of caffeic acid (CA) derivatives 7a-j were synthesized via etherification and coupling action and their chemical structures were elucidated spectroscopically. Motivated by the various biological activities displayed by CA derivatives such as anti-inflammatory, antiviral, anticancer and antioxidant and also based on its extensively consumption in the human diet. In the present work, the newly synthesized compounds 7a-j were evaluated for anti-inflammatory and analgesic action and most of them exerted comparable activity to the reference compound celecoxib. Further, ulcer indexes for the most active compounds were calculated and most of them showed less ulcerogenic effect than the reference drug. Among the title series 7a-j, compounds 7f and 7g with electron withdrawing bromo and chloro group respectively, at the para position of the phenoxy ring was showed good activity compared to all other compounds. Interestingly, the COX-I/COX-II activity ratio of potent compounds 7f and7g showed an almost equal inhibitory effect on both isoenzymes. Further, molecular docking studies have been performed for the potent compounds which showed statistically significant result.
Synthesis and xanthine oxidase inhibitory activity of 7-methyl-2- (phenoxymethyl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-5-one derivatives
Sathisha,Khanum, Shaukath A.,Chandra, J.N. Narendra Sharath,Ayisha,Balaji,Marathe, Gopal K.,Gopal, Shubha,Rangappa
experimental part, p. 211 - 220 (2011/03/17)
An elevated level of blood uric acid (hyperuricemia) is the underlying cause of gout. Xanthine oxidase is the key enzyme that catalyzes the oxidation of hypoxanthine to xanthine and then to uric acid. Allopurinol, a widely used xanthine oxidase inhibitor is the most commonly used drug to treat gout. However, a small but significant portion of the population suffers from adverse effects of allopurinol that includes gastrointestinal upset, skin rashes and hypersensitivity reactions. Moreover, an elevated level of uric acid is considered as an independent risk factor for cardiovascular diseases. Therefore use of allopurinol-like drugs with minimum side effects is the ideal drug of choice against gout. In this study, we report the synthesis of a series of pyrimidin-5-one analogues as effective and a new class of xanthine oxidase inhibitors. All the synthesized pyrimidin-5-one analogues are characterized by spectroscopic techniques and elemental analysis. Four (6a, 6b, 6d and 6f) out of 20 synthesized molecules in this class showed good inhibition against three different sources of xanthine oxidase, which were more potent than allopurinol based on their respective IC50 values. Molecular modeling and docking studies revealed that the molecule 6a has very good interactions with the Molybdenum-Oxygen-Sulfur (MOS) complex a key component in xanthine oxidase. These results highlight the identification of a new class of xanthine oxidase inhibitors that have potential to be more efficacious, than allopurinol, to treat gout and possibly against cardiovascular diseases.
Synthesis and screening of certain aryloxyacetylaminoguanidines as potential antihypertensive agents
Osman,Botros,Kandeel,Khalil,Abd El-Latif
, p. 446 - 455 (2007/10/03)
Ethyl aryloxyacetates (2a-k) have been synthesized either by the esterification of aryloxyacetic acids (1a-j) with ethanol in the presence of concentrated sulphuric acid or by reacting potassium naphthoxides with ethyl chloroacetate in dimethylformamide. Hydrazinolysis of either 1a, b, d, f, j or 2a-k furnishes the corresponding hydrazides (3). On the other hand, the acid chlorides (4f-h) have been prepared via the reaction of 1a-f with thionyl chloride in dry benzene, which on refluxing with aminoguanidine bicarbonate in dry benzene give the target aminoguanidine hydrochlorides (5a-h). Meanwhile, the desired aminoguanidine sulphates (5a-e) have been obtained by condensing 2a-e with S-methylisothiourea sulphate in aqueous ethanol. Additionally, the new aminotriazole sulphates (6a-h) are obtained either by refluxing 2a-h with S-methylisothiourea sulphate or by fusion of 1a,b, h, j with aminoguanidine sulphate. Structures of the new compounds are based on elemental analyses and IR, 1 HNMR and mass spectral data. Pharmacological screening, indicates that some of the newly synthesized compounds exhibit significant antihypertensive activity in both normal and renal hypertensive rats. Compound 5b produces significant decrease in the heart rate of normal rats. Compounds 5f and 5g have no significant effect. Compounds 5f, g, h have inhibition effect on the isolated rabbit intestine.
