Synthesis of Some New Azoloazines with Potent Anti‐inflammatory and Analgesic Activity

Starting from pyrimidine‐2‐thiones, a set of new fused triazoles, thiazoles, and thiazines has been obtained. The mechanistic pathway and structures of all the novel products were ascertained on the foundation of spectral information and elemental analyses. The analgesic and anti‐inflammatory activities of all the prepared compounds were predestined. The outcomes disclosed that all of the examined samples revealed potent activity. Moreover, the relation between the structure and the activity has been researched.     

Pyrazole‐1‐carbothioamide as a Potent Precursor for Synthesis of Some New N‐heterocycles of Potential Biological Activity

Herein, we reported the efficient synthesis of new azoles as bio‐functional analogs, employing the easily obtainable N‐acetyl‐3,5‐diphenyl‐4,5‐dihydro‐1H‐pyrazole‐1‐carbothioamide ( 1 ), as a versatile precursor. The structures of the newly synthesized compounds were elucidated based on their IR, ¹H NMR, and ¹³C NMR mass spectral and elemental analysis. Furthermore, some selected compounds were evaluated in vitro for their antimicrobial activities. The preliminary bioassay results indicate that the majority of the tested compounds exhibited significant antimicrobial activity. Compounds 12 , 11 , 18 , 30 , 22 , 3 , and 2 were found to be the most potent against the tested microorganisms with minimum inhibitory concentration ≤ (12.25 μg/mL), indicating that conjugates bearing thiazole moiety, as well as those with N‐substituted electron‐withdrawing groups, exhibited higher potency than the rest of other compounds.     

Synthesis of Some Newer Analogues of 4‐Hydroxyphenyl Acetic Acid as Potent Anti‐Inflammatory Agents

A series of 1,3,4‐oxadiazole and 1,2,4‐triazole derivatives of 4‐hydroxyphenyl acetic acid have been synthesized and evaluated for their anti‐inflammatory activity by carrageenan induced rat paw edema method. The compounds, which showed good anti‐inflammatory activity, were screened for their ulcerogenic and lipid peroxidation activities.     

Synthesis and Antimicrobial Activity of Some New N‐substituted‐5‐arylidene‐thiazolidine‐2,4‐diones

A total of 17 new N‐substituted derivatives ( 2b , 2c , 2d , 2e , 2f , 2g , 2h , 2i , 2j , 2k and 3b , 3c , 3d , 3e , 3f , 3g , 3h ) of 5‐((2‐phenylthiazol‐4‐yl)methylene) thiazolidine‐2,4‐dione ( 2a ) and 5‐(2,6‐dichloro‐ benzylidene)thiazolidine‐2,4‐dione ( 3a ) were synthesized. The structural elucidation of the newly synthesized compounds was based on elemental analysis and spectroscopic data (MS, ¹H NMR, ¹³C NMR), and their antimicrobial activities were assessed in vitro against several strains of Gram‐positive and Gram‐negative bacteria and one fungal strain (Candida albicans) as growth inhibition diameter. Some of them showed modest to good antibacterial activity against Gram‐negative Escherichia coli and Salmonella typhimurium and Gram‐positive Staphylococcus aureus, Bacillus cereus, and Enterococcus fecalis bacterial strains, whereas almost all the compounds were inactive against Listeria monocytogenes. All of the synthesized compounds showed moderate to very good activity against C. albicans.     

N-取代苄基-4-羟基-4-取代哌啶衍生物的合成及初步抗白血病活性

为了寻找对白血病细胞系增殖有较高抑制活性的先导化合物,本文以取代苄胺为原料,经Michael加成,Dieckmann缩合,水解脱羧和与Grignard试剂反应合成了12个均未见文献报道的目标化合物6a─6l,结构均经过1H NMR、IR、MS及元素分析确证。并采用MTT法对目标化合物进行了对白血病K562细胞系增殖影响的初步测试,结果表明大部分具有较好的抑制细胞系增殖的活性,有潜在的抗白血病活性。     

Synthesis and Preliminary Anti‐bacterial Activity of Some 4‐Substituted‐N1‐2‐pyridylsulfanilamide Derivatives

2‐Amino‐4‐ethoxycarbonylpyridine 1 was used as a starting material in the synthesis of some 4‐substituted‐N¹‐2‐pyridylsulfanilamide derivatives to evaluate their antimicrobial activity. The obtained compounds were of no particular effect against the tested organisms except for a noticeable inhibition of B. subtilis, which was of varying extents but remained clearly significant.     

Synthesis of Some Novel Heterocycles Bearing Thiadiazoles as Potent Anti‐inflammatory and Analgesic Agents

2‐Bromoacetyl‐3‐phenyl‐1,3,4‐thiadiazole derivative was synthesized and reacted with a number of heterocyclic amines to give a series of fused imidazole derivatives. Also, reaction of 2‐bromoacetyl‐3‐phenyl‐1,3,4‐thiadiazole with o‐phenylene diamine and 2‐aminothiophenol yielded the respective products. Moreover, reaction of 2‐bromoacetyl‐3‐phenyl‐1,3,4‐thiadiazole with thiourea, thiosemicarbazide, thiocarbahydrazide gave the respective thiazoles. The structures of all the novel products were elucidated on the basis of elemental analysis and spectral data. In addition, the biological activity of the newly synthesized compounds was evaluated, and the results obtained indicate their potency as anti‐inflammatory, analgesic, and anti‐ulcer agents. The binding mechanism of the most active compounds was studied using MOE to analyze the molecular interactions.     

Utility of Bis‐Hydrazonoyl Chlorides as Precursors for Synthesis of New Functionalized Bis‐Thiadiazoles as Potent Antimicrobial Agents

N′,N″‐([1,1’‐Biphenyl]‐4,4′‐diyl)bis(2‐oxopropanehydrazonoyl chloride) is considered to be the key intermediate for the synthesis of a variety bis‐1,3,4‐thiadiazole derivatives in one step methodology with good yields by reaction of with a series of hydrazinecarbodithioate derivatives 2a–e , 6a , b , and 8a–e . The assigned structures for all the newly synthesized compounds were confirmed on the basis of elemental analyses and spectral data (infrared, NMR, and mass), and the mechanisms of their formation were also discussed. Moreover, the antimicrobial activity for twelve selected products was screened, and the results obtained exploring the high potency of some of the tested compounds compared with the employed standard bactericides and fungicides. In addition, the minimum inhibitory concentration of the tested compounds was determined, and the results obtained exploring the high potency of three of the tested compounds against all the tested microorganisms.     

Utility of Benzoxazin‐4‐one and 3‐Aminoquinazolin‐4‐one Derivatives as Precursors for Construction of Potent Insecticidal Heterocycles

In demanding to develop new insecticidal agents, both of 2‐pentylbenzoxazin‐4‐one 1 and 3‐amino‐2‐pentylquinazolin‐4‐one 6 derivatives were subjected to react with different nucleophilic agents, for example, ammonia, o‐phenylenediamine, hydrazine hydrate, and hydroxylamine hydrochloride, and sulfur nucleophile, for example, phosphorous pentasulfide, to construct different heterocyclic systems. The structural elucidations of the synthesized compounds were ascertained from the elemental analyses and the spectral data. Assessment of the biological potency for some of the synthesized compounds as insecticidal agents was evaluated against two different insects named Mythimna separata and Nilaparvata lugens.     

Synthesis,Bioactivities and Structure Activity Relationship of N‐4‐Methyl‐1,2,3‐thiadiazole‐5‐carbonyl‐N′‐phenyl Ureas

Twenty nine novel N‐4‐methyl‐1,2,3‐thiadiazole‐5‐carbonyl‐N′‐phenyl ureas were designed and synthesized, and their structures were confirmed by proton nuclear magnetic resonance (¹H NMR), infra red spectroscopy (IR) and high‐resolution mass spectroscopy (HRMS). Compounds V‐9 , V‐11 , V‐12 , V‐15 , V‐19 , V‐21 , V‐22 and V‐24 exhibit excellent activity against Culex pipiens pallens. Compounds V‐12 and V‐22 present good insecticidal activity against Plutella xylostella L. Their median lethal concentrations (LC₅₀) are 164.15 and 89.69 mg·L^?1, respectively. Compound V‐11 also has potential wide spectrum of fungicide activity. Its median effective concentrations (EC₅₀) detected from 3.82 µg·mL^?1 against Physalospora piricola to 31.60 µg·mL^?1 against Cercospora arachidicola. Compounds V‐15 and V‐24 show outstanding induction activities as same as positive controls TDL and ningnanmycin, furthermore V‐24 has the highest induction activity of 41.85%±4.43%. To elucidate the structure activity relationship in these compounds, a 3D‐QSAR model has been built. The established model showed a reliable predicting ability with q² values of 0.643 and r² values of 0.982.     

Efficient Synthesis of Some New 1,3,4‐Thiadiazoles and 1,2,4‐Triazoles Linked to Pyrazolylcoumarin Ring System as Potent 5α‐Reductase Inhibitors

The current study in this article concerned with construction of five‐membered heterocycles with multiple heteroatoms as nitrogen and sulfur from readily available starting materials and reagents. Treatment of 1‐(2‐oxo‐2H‐chromene‐3‐carbonyl)‐3‐phenyl‐1H‐pyrazol‐5(4H)‐one with each of phenylisothiocyanate in alcoholic potassium hydroxide and carbon disulfide in basic medium gave rise to a thioanilide and methylthio derivatives, respectively. Treatment of the latter compounds with a variety of hydrazonoyl halides resulted in construction of thiadiazole moiety linked to pyrazole ring. Furthermore, triazole derivatives were synthesized from the thioanilide derivative through its reaction with methyl iodide followed by reaction with hydrazonoyl halides. 5α‐Reductase inhibition activity for the prepared compounds was investigated against the reference drug anastrozole, and the results showed that the inhibition activity of compounds 5g and 11g is more potent than anastrozole. Also compounds bearing triazole moiety is more potent than compounds bearing thiadiazole one. Moreover, the anti‐prostate cancer screening anti‐androgenic bioassay in human prostate cancer cells for the tested compounds was evaluated, and the results showed great inhibition growth and potential antiandrogens.     

N‐(Substituted benzyl)‐3,5‐bis(benzylidene)‐4‐piperidones: Synthesis and Preliminary Anti‐leukemia Activity (I)

A series of novel N‐(substituted benzyl)‐3,5‐bis(benzylidene)‐4‐piperidones 5a – 5o were synthesized with substituted benzylamines as raw materials via a series of Michael addition, Dieckmann condensation, hydrolysis decarboxylation and aldol condensation. The structures were confirmed by ¹H NMR, IR, MS techniques and elemental analysis. Assay‐based antiproliferative activity study using leukemic cell lines K562 revealed that most of the title compounds have high effectiveness in inhibiting leukemia K562 cells proliferation, among which the compounds 5g (IC₅₀=7.81 µg·mL⁻¹), 5k (IC₅₀=6.35 µg·mL⁻¹), 5l (IC₅₀=7.20 µg·mL⁻¹), and 5o (IC₅₀=5.79 µg·mL⁻¹) have better inhibition activities than standard 5‐fluorouracil (IC₅₀=8.56 µg·mL⁻¹).     

Microwave‐assisted Synthesis of Novel 3,4‐Bis‐chalcone‐N‐arylpyrazoles and Their Anti‐inflammatory Activity

A series of 3,4‐bis‐chalcone‐N‐arylpyrazoles 3a‐h was prepared conveniently from diacetyl pyrazoles 2a,b . All reactions were carried out under conventional thermal heating and/or microwave irradiation. The structure of the latter functionally pyrazoles was confirmed under the bases of their IR, mass, ¹H NMR and ¹³C NMR. The X‐ray diffraction of compound 3e not only confirmed the chemical structure of 3a‐h , but also showed the E configuration of their chalcone moieties. Treatment of compound 3e with phenyl hydrazine in presence of acetic acid afforded the tri‐pyrazle 4 . The anti‐inflammatory activity of the newly synthesized compounds was investigated. Some of these compounds showed a moderate activity when compared with indomethacin as a reference drug. The combination between chalcone and pyrazole moieties revealed a variable effect in anti‐inflammatory activity.     

Synthesis of indole‐4‐carboxaldehydes and 4‐acetylindole from N‐alkyl‐5‐aminoisoquinolinium salts

N‐Alkyl‐5‐aminoisoquinolinium salts ( 8a‐d ) are converted into indole‐4‐carboxaldehydes ( 1a‐c ) on heating in a two phase alkyl acetate‐water system containing an excess of a 2:1 sodium bisulfite‐sodium sulfite mixture. 4‐Acetylindole 1e is prepared in the same way from 1‐methyl‐2‐cyanomethylisoquinolinium bromide 8f .     

Friedländer condensation of 5‐aminopyrazole‐4‐carbaldehydes with reactive α‐methylene ketones: Synthesis of pyrazolo[3,4‐b]pyridines

A series of 1,3,6‐trisubstituted and 1,3,5,6‐tetrasubstituted pyrazolo[3,4‐b]pyridines 5 has been synthesized by Friedlander condensation of 5‐arninopyrazole‐4‐carbaldehydes 3 with α‐methylene ketones such as acetone (4a) or acetophenones 4b‐f with potassium hydroxide as basic catalyst. Condensation of 5‐aminopyrazole‐4‐carbaldehydes 3 and unsymmetric dialkylketones 6 yielded mixtures of isomeric pyra‐zolo[3,4‐b]pyridine derivatives 7 and 8 . Condensation of 5‐aminopyrazole‐4‐carbaldehydes 3 with CH‐acidic acylacetonitriles 9 and acylacetates 11 with piperidine as basic catalyst yielded pyrazolo[3,4‐b]pyri‐dine‐5‐carbonitriles 10 and pyrazolo[3,4‐b]pyridine‐5‐carboxylates 12 ; with diethyl malonate 13 as CH‐acidic component, pyrazolo[3,4‐b]pyridin‐6‐ones 14 were obtained.