- Synthesis of Some Novel Thiazolo[3,2-a]pyrimidine and Pyrimido[2,1-b][1,3]thiazine Derivatives and their Antimicrobial Evaluation
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A 2-(2-Mercapto-4-(4-phenoxyphenyl)-6-(thiophen-2-yl)-1,6-dihydropyrimidin-5-yl) acetic acid was used as a reactive key precursor to design various pyrimidine derivatives such as thiazolo[3,2-a]pyrimidines and pyrimido[2,1-b][1,3]thiazines. The chemical s
- Behalo, Mohamed S.
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- In silico designing, in vitro and in vivo evaluation of potential PPAR-γ agonists derived from aryl propionic acid scaffold
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Attributed to several side effects, especially on hepatic tissues and body weight, there is always an urge of innovation and upgrading in already existing medication being used in maintaining diabetic condition. Therefore, in the present work, forty-eight molecules derived from arylpropionic acid scaffold were synthesized and their evaluation against diabetes was carried out. The synthesis of these molecules attributed to excellent dock score displayed by all the structures performed against PPAR-γ receptor site. Subsequently, all the derivatives were primarily deduced for their antidiabetic potential by OGTT. The compounds that showed significant antidiabetic activity in OGT Test and also exhibited high dock scores were assessed further by in vitro PPAR transactivation assay to assure analogy between in vivo and in vitro studies. The antidiabetic activity of these active compounds was then evaluated on STZ induced diabetic model in vivo. The most active compounds were scrutinized for its effect on PPAR-γ gene expression and hepatotoxic effect. Finally, it was recapitulated that these derivatives can provide a new prospect towards the development of antidiabetic agents with fewer side effects.
- Kharbanda, Chetna,Alam, Mohammad Sarwar,Hamid, Hinna,Ali, Yakub,Nazreen, Syed,Dhulap, Abhijeet,Alam, Perwez,Pasha
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- PHARMACEUTICAL COMPOUNDS FOR THE TREATMENT OF COMPLEMENT MEDIATED DISORDERS
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This disclosure provides pharmaceutical compounds to treat medical disorders, such as complement-mediated disorders, including complement Cl -mediated disorders.
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Page/Page column 339-341
(2020/10/18)
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- Synthesis, anti-convulsant activity and molecular docking study of novel thiazole pyridazinone hybrid analogues
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Pyridazinone analogues have been known to be potential candidates for anticonvulsant agents. We have identified several pyridazinone-based anticonvulsant agents. As a continuation to our previous research, a series of hybrid pyridazinone-thiazole connected through amide linkage were designed and synthesized. Among these, compound SP-5F demonstrated significant anticonvulsant activity with median effective dose of 24.38 mg/kg (MES) and 88.23 mg/kg (scPTz). Results of GABA estimation showed a marked increase in the GABA level when compared with control. Molecular docking studies at the active site of GABA receptor, further confirmed the GABA modulatory effects of SP-5F.
- Khisal, Subuhi,Mishra, Ravinesh,Partap, Sangh,Siddiqui, Aness Ahmad,Yar, Mohammad Shahar
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- Design, Synthesis, and Pharmacological Screening of Pyridazinone Hybrids as Anticonvulsant Agents
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A series of new hybrid benzimidazole containing pyridazinones derivatives were designed and synthesized in accordance with the pharmacophoric requirements essential for the anticonvulsant activity. The synthesized compounds were evaluated for anticonvulsant activity on mice by the gold standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models. Among the compounds tested, SS-4F showed significant anticonvulsant activity in both the screens with ED50 values of 25.10 and 85.33 mg/kg in the MES and scPTZ screens, respectively. Compound SS-4F emerged as safer and effective anticonvulsant due to its several-fold higher protective indices. Further, the gamma-aminobutyric acid (GABA) estimation result showed a marked increase in the GABA level (1.7-fold) as compared to the control, which was further confirmed by good binding properties with the GABAA receptor.
- Partap, Sangh,Yar, Mohammad Shahar,Hassan, Md. Zaheen,Akhtar, Md. Jawaid,Siddiqui, Anees A.
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- Cobalt-catalyzed oxidative cyclization of gem-disubstituted conjugated alkenols
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Aryl gem-disubstituted conjugated alkenols underwent oxidative cyclization affording 2,5,5-trisubstituted tetrahydrofurans in reasonable yields and good diastereoselectivities using the reductive termination variation of the Mukaiyama aerobic oxidative reaction. Under oxidative termination, the same alkenols produced diols and ketonic by-products via the double hydration and beta-scission competing pathways. Furthermore, the differences in alkenol reactivity under the reductive and oxidative termination conditions were investigated.
- Alves, Tania M.F.,Costa, Mateus O.,Bispo, Beatriz A.D.,Pedrosa, Fabiana L.,Ferreira, Marco A.B.
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supporting information
p. 3334 - 3338
(2016/07/11)
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- One-pot synthesis of tetralin derivatives from 3-benzoylpropionic acids: Indium-catalyzed hydrosilylation of ketones and carboxylic acids and intramolecular cyclization
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This reducing system was composed of a small amount (1 mol%) of In(OAc)3, Me2PhSiH, and I2 that effectively catalyzed the hydrosilylation of two different carbonyl groups, a ketone and a carboxylic acid found in 3-benzoylpropionic acids, followed by a subsequent intramolecular cyclization that led to the one-pot preparation of tetralin derivatives.
- Sakai, Norio,Kobayashi, Taichi,Ogiwara, Yohei
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supporting information
p. 1503 - 1505
(2015/11/24)
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- Synthesis, antiproliferative and anti-inflammatory activities of some novel 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2H)-ones
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Sixteen new 6-aryl-2-(p-(methanesulfonyl)phenyl)-4,5-dihydropyridazi-3(2 H)-ones (2a-p) were synthesized and tested for in vitro anticancer and in vivo anti-inflammatory activities. Eleven (2b, 2d , 2-ej and 2m-p) of the obtained compounds were screened for their antiproliferative activity towards 60 human cancer cell lines by the National Cancer Institute (USA). Compound 2f showed remarkable activity with GI50 less than 1 μM on 36 human tumor cell lines and has been referred to Biological Evaluation Committee (NCI) for advance study. Compound 2g also displayed promising antiproliferative activity against 20 different cell lines with GI50 less than 1 μM. Compounds 2k and 2n were found to have a comparable anti-inflammatory activity to that of standard drug etoricoxib in carrageenan-induced rat hind paw edema model at 5 h.
- Ovais, Syed,Javed, Kalim,Yaseen, Shafiya,Bashir, Rafia,Rathore, Pooja,Yaseen, Raed,Hameed, Alhamzah D.,Samim, Mohammad
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p. 352 - 358
(2013/10/01)
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- Synthesis and biological evaluation of some novel sulfamoylphenyl- pyridazinone as anti-inflammatory agents (Part-II)
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Seven novel 6-aryl-2-(p-sulfamoylphenyl)-4,5-dihydropyridazin-3(2H)-ones (2a-g) were synthesized by the condensation of appropriate aroylpropionic acid and 4-hydrazinobenzenesulfonamide hydrochloride in ethanol. Structure of all compounds have been elucidated by elemental analysis, IR, 1H NMR, 13C NMR, DEPT and MS spectrscopy. These compounds were tested for their anti-inflammatory activity in carrageenan-induced rat paw edema model. Compound 2b exhibited anti-inflammatory activity comparable to that of celecoxib (at 5h). Two other compounds 2d and 2g showed promising anti-inflammatory activity (edema reduction more than 80% at 5h). These compounds (2b, 2d and 2g) did not produce any ulceration in gastric region.
- Bashir, Rafia,Yaseen, Shafiya,Ovais, Syed,Ahmad, Shamim,Hamid, Hinna,Alam,Samim, Mohammad,Javed, Kalim
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experimental part
p. 92 - 96
(2012/05/19)
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- Novel selective thiazoleacetic acids as CRTH2 antagonists developed from in silico derived hits. Part 1
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Structure-activity relationships of three related series of 4-phenylthiazol-5-ylacetic acids, derived from two hits emanating from a focused library obtained by in silico screening, have been explored as CRTH2 (chemoattractant receptor-homologous molecule expressed on Th2 cells) antagonists. Several compounds with double digit nanomolar binding affinity and full antagonistic efficacy for human CRTH2 receptor were obtained in all subclasses. The most potent compound was [2-(4-chloro-benzyl)-4-(4-phenoxy-phenyl)-thiazol-5-yl]acetic acid having an binding affinity of 3.7 nM and functional antagonistic effect of 66 nM in a BRET and 12 nM in a cAMP assay with no functional activity for the other PGD2 DP receptor (27 μM in cAMP).
- Rist, ystein,Grimstrup, Marie,Receveur, Jean-Marie,Frimurer, Thomas M.,Ulven, Trond,Kostenis, Evi,Hoegberg, Thomas
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scheme or table
p. 1177 - 1180
(2010/06/15)
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- Amide derivatives of sulfonamides and isoniazid: Synthesis and biological evaluation
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In the present study, various amide derivatives of sulfanilamide, sulfamethoxazole, sulfadiazine, dapsone and isoniazid have been synthesized by condensing them with appropriate 4-oxo-4-(4-substituted phenyl)butanoic acid moiety. The compounds have been evaluated for their antiinflammatory, ulcerogenic and antibacterial activities. Their structures were established on the basis of elemental analysis, 1H NMR and mass spectral data. Some of the compounds were found to have significant antiinflammatory and antibacterial activities. Additionally, these derivatives were low in their ulcerogenic action, which is the main side effect of commonly used NSAIDs.
- Husain, Asif
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experimental part
p. 513 - 521
(2010/01/16)
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- Synthesis and in-vitro antifungal activity of 6-substituted-phenyl-2- {[(4′-substituted phenyl-5′-thioxo)-1,2,4-triazol-3-yl]-methyl}-2,3, 4,5-tetrahydropyridazin-3-one derivatives
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The synthetic pathway for 6-substituted phenyl-2-[{(4′-substituted phenyl-5′-thioxo)-1,2,4-triazol-3-yl}-methyl]-2,3,4,5-tetrahydropyridazin- 3-one compounds was achieved by a sequence of reactions starting from respective aryl hydrocarbons and is illustrated in Scheme1. All the compounds were tested for their in vitro antifungal activity on five fungal species, namely Candida albicans, Trichophyton rubrum, Aspergillus flavus, Aspergillus niger and Penicillium citrinium. The chloro substituent derivative (compound 5g) showed the highest activity against all the fungal species. The MIC of the standard drug voriconazole was between 0.10 - 0.40 μg/mL against all the fungal species except A. fumigatus. The two electronegative groups of Cl were increasing the activity of 1,2,4-triazole. As we increased the bulky group or aromatic group on benzene ring, there was a decrease of activity as in case of compound l.
- Siddiqui, Anees A.,Ahamad, Syed Rizwan,Mir, Mohammed Shehroz,Hussain, Syed Akhtar,Raish, Mohammed,Kaur, Ravindra
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experimental part
p. 223 - 228
(2009/04/04)
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- Synthesis and antimicrobial activity of some novel oxadiazole derivatives
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A series of 5-{3′-oxo-6′-(substituted aryl)-2′,3′, 4′,5′-tetrahydropyridazin-2′-ylmethyl}-2-substituted 1,3,4-oxadiazole has been synthesized. Appropriate aromatic hydrocarbon reacts with succinic anhydride in the presence of AlCl3 to yield β-aroyl propionic acid (1a). The corresponding acid is cyclized with hydrazine hydrate to give 6-(substituted aryl)-2,3,4,5-tetrahydro-3-pyridazinone (1b).This ntermediate after reaction with ethyl bromoacetate, was hydrazinolyzed into 3-oxo-6-(substituted aryl)-2, 3, 4, 5-tetrahydropyridazinyl acetohydrazide (1c).The resulting product was converted into 5-{3′-oxo-6′-(substituted aryl)-2′,3′,4′,5′- tetrahydropyridazin-2′-ylmethyl]-2-substituted 1,3,4-oxadiazole (Scheme 1). All the final compounds were structurally elucidated on the basis of IR, 1H-NMR, MS data and elemental analysis and screened for antibacterial, antifungal and antitubercular activity. All the compounds are evaluated for their antibacterial activity against E. coli, S. aureus, Miavcoccus luteus and Klebsiella pneumoniae by using cup plate technique in the nutrient agar at 100 μg/mL concentration. Antitubercular activity was determined using the BACTEC 460 system. Stock solutions of test compounds were prepared in DMSO. MIC of rifampin was calculated by established procedures.All the synthesized compounds were screened at 6.25 μg/mL against M. tuberculosis H37 Rv comparable with that of standard rifampicin and isoniazid. All the final compounds were evaluated for antifungal activity against C. albicans and C. neoformans by using cup-plate method in the Sabouraud agar media The zone of inhibition (mm) of each compound was determined and compared with standard drug fluconazole.
- Islam, Mojahidul,Siddiqui, Anees A.,Rajesh, Ramadoss,Bakht, Afroz,Goyal, Sunil
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experimental part
p. 441 - 447
(2009/04/07)
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- 2-Arylidene-4-(4-phenoxy-phenyl)but-3-en-4-olides: Synthesis, reactions and biological activity
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2-Arylidene-4-(4-phenoxy-phenyl)but-3-en-4-olides (1-17) were prepared from 3-(4-phenoxy-benzoyl)propionic acid and aromatic aldehydes. Some of the selected butenolides were reacted with ammonia and benzylamine to give corresponding 3-arylidene-5-(4-pheno
- Husain, Asif,Khan,Hasan,Alam
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p. 1394 - 1404
(2007/10/03)
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- Syntheses and antiinflammatory activity of some 6-aryl-2,3,4,5-tetrahydro-3-pyridazinones
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6-Aryl-2, 3, 4, 5-tetrahydro-3-pyridazinones (2c-22c) are obtained by dehydrocyclisation of various hydrazides formed by the reaction of appropriate methyl β-aroylpropionate and hydrazine hydrate in the presence of anhydrous sodium acetate. They show promising antiinflammatory activity during their evaluation by carrageenin induced paw edema test in rats.
- Khan,Siddiqui
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p. 614 - 619
(2007/10/03)
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- Studies on antihyperlipidemic agents. I. Synthesis and hypolipidemic activities of phenoxyphenyl alkanoic acid derivatives
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The alkanoic acids containing phenoxyphenyl moiety at ω-position were prepared and tested for hypolipidemic property. Some of the compounds showed hypoglycemic activity besides hypolipolipidemic one. Further study on the selected compound, 3-[4-(4-chlorophenoxy)benzoyl]propionic acid (8) revealed that it increased insulin sensitivity of adipose tissue of obese and diabetic mice (KKA(y)). The structure-activity relationship was discussed briefly.
- Kawamatsu,Saraie,Imamiya,Nishikawa,Hamuro
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p. 454 - 458
(2007/10/02)
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- Fenbufen, a new anti inflammatory analgesic: synthesis and structure activity relationships of analogs
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100 analogs of fenbufen were prepared and tested using the carrageenan, polyarthritis, and UV erythema anti inflammatory tests and the 2 phenyl 1,4 benzoquinone writhing and inflamed paw pressure analgesic tests. Only 3 retained the same full spectrum of activity as fenbufen: dl 4 (4 biphenylyl) 4 hydroxybutyric acid, dl 4 (4 biphenylyl) 1,4 butanediol, and 4 biphenylacetic acid. Fenbufen had the same spectrum of activity as aspirin, phenylbutazone, and indomethacin in the 5 tests. In addition, dose response derived potencies show fenbufen more potent than aspirin and at least as potent as phenylbutazone in all 5 tests. Two related compounds were generally similar.
- Child,Osterberg,Sloboda,Tomcufcik
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p. 466 - 476
(2007/10/05)
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