Synthesis and Reactions of 3‐Methylthiazolo[3,2‐a]Benzimidazole‐2‐Carboxylic Acid Hydrazide: Synthesis of Some New Pyrazole, 1,3‐Thiazoline, 1,2,4‐Triazole and 1,2,4‐Triazolo[3,4‐b]‐1,3,4‐Thiadiazine Derivatives Pendant to Thiazolo[3,2‐a]Benzimidazole Moiety

The reaction of 3‐methylthiazolo[3,2‐a]benzimidazole‐2‐carboxylic acid ethyl ester (1) with hydrazine hydrate gives the hydrazide 2 which reacts with CS₂/KOH to afford the potassium salt 3. Treatment of 3 with l‐aryl‐2‐bromoethanones 4a,b afforded the 1,3‐thiazoline derivatives 6a,b, respectively, while the reaction of 3 with hydrazine hydrate afforded 1,2,4‐triazole‐3‐thione derivative 9. The reaction of 9 with l‐aryl‐2‐bromoethanones 4a,b and with hydrazonyl chlorides 11a,b gave the 1,2,4‐triazolo[3,4‐b]‐1,3,4‐thiadiazine derivatives 10a,b and 12a,b, respectively. Treatment of hydrazide 2 with phenyl isothiocyanate in refluxing benzene gave the thiosemicarbazide derivative 16. The latter reaction gave 1,3,4‐oxadiazole derivative 17 when benzene was replaced by DMF. Cyclization of the thiosemicarbazide derivative 16 with NaOH resulted in the formation of the 1,2,4‐triazole‐3‐thione derivative 18.     

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.     

Design and Synthesis of 3‐Aryl‐5‐Alicylic‐[1,2,4]‐oxadiazoles as Novel Platelet Aggregation Inhibitors

A series of 4‐[2‐(alicyclic‐[1,2,4]oxadiazol‐3‐yl)phenoxy]‐butyric acids were synthesized from N‐hydroxy‐2‐isopropoxy benzamidine in 4 steps with good yields. These [1,2,4]oxadiazoles are novel platelet aggregation inhibitors preventing human platelet aggregation induced by thromboxane derivative U44,619 and adenosine diphosphate. A structure‐activity‐relationship study revealed that the potency for these 5‐oxadiazoles increases with the increase in the ring size of the alicylic rings. Derivative 8f may be useful as a template for the design of more potent anti‐platelet agents.     

One‐pot Synthesis of 2,5‐Disubstituted‐1,3,4‐oxadiazoles Based on the Reaction of N,N‐Dimethyl Amides with Acid Hydrazides

Convenient and efficient one pot method for the synthesis of 2,5‐disubstituted‐1,3,4‐oxadiazoles based on the reaction of N,N‐dimethyl amides with acid hydrazides has been developed. The methodology is applied to a wide range of difference aryl hydrazide and difference N,N‐dimethyl amides to 2,5‐disubstituted‐1,3,4‐oxadiazoles yield the in good to excellent yields. It will be possible wide useful application in synthesis.     

Synthesis and Antimicrobial Activity of Some Condensed [4‐(2,4,6‐Trimethylphenyl)‐1(2H)‐oxo‐phthalazin‐2‐yl]acetic Acid Hydrazide

Some new 1,2,4‐triazolo‐, 1,3,4‐oxadiazolo‐, 1,3,4‐thiadiazol‐, and pyrazolo‐2,4,6‐trimethylphenyl‐1(2H)‐oxo‐phthalazine derivatives were synthesized and identified by IR, ¹H NMR, ¹³C NMR, MS and elemental analysis. The new compounds were synthesized with the objective of studying their antimicrobial activity.     

Synthesis,Antimicrobial and Anti‐HIV Activity of Some Novel Benzenesulfonamides Bearing 2,5‐Disubstituted‐1,3,4‐Oxadiazole Moiety

Twelve novel primary ( 4a‐c , 5a‐c ) and secondary ( 4d‐f, 5d‐f ) benzenesulfonamides bearing 2,5‐disubstituted‐1,3,4‐oxadiazole moiety have successfully been prepared by direct chlorosulfonation of phenyl substitutent present on the 2‐position of 5‐mercapto‐1,3,4‐oxadiazoles 2a‐c and their methylhio derivatives 3a‐c using chlorosulfonic acid under anhydrous conditions. Structures of the synthesized compounds were established by their physical and spectral data. Some of the synthesized compounds have been screened in vitro for their antimicrobial and anti‐HIV activity; the results were in accordance with SAR.     

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 Tetrazoloquinoline‐Based Mono‐ and Bisphosphonate Esters as Potent Anti‐Inflammatory Agents

Several new α‐alkoxy‐ and α‐hydroxyphosphonate derivatives of tetrazole‐quinolines were synthesized from the reaction of 2‐azidoquinolines 3‐carboxaldehyde 1a,b with trialkyl phosphites and dialkyl phosphites. On the other hand, azaphospholes 12a,b were obtained by treating 1a,b with tris(dimethylamino)phosphine. Furthermore, Perkin‐type condensation of 1a,b and tetraethyl methylenebisphosphonate provided the corresponding tetrazoloquinoline‐based bisphosphonate esters 14a,b . Based on the prediction results (PASS program), the anti‐inflammatory activity of the prepared compounds was determined in vivo by the acute carrageenin‐induced paw edema in rats. Many of the new compounds exhibit considerable anti‐inflammatory properties at a dose of 50 mg/kg body weight. Especially 14a and 14b revealed remarkable activities compared with indomethacin, which was used as a reference standard in this study.     

A New Route to Synthesis of 3,6‐Diaryl‐1,2,4‐triazolo[3,4‐b]1,3,4‐oxadiazoles

Five new 3,6‐diaryl‐1,2,4‐triazolo[3,4‐b]1,3,4‐oxadiazole derivatives were synthesized by 9 steps from aromatic acids and evaluated for their activities of anticancer and antibacteria. The structures of all new compounds synthesized were elucidated by MS, IR, ¹HNMR and HRMS.     

Pharmacological Evaluation of Novel Organoiron Dendrimers as Antimicrobial and Anti‐Inflammatory Agents

The synthesis of a novel and attractive class of nonsteroidal anti‐inflammatory and antimicrobial organoiron dendrimers attached to the well‐known drug ibuprofen is achieved. The structures of these dendrimers are established by spectroscopic and analytical techniques. The antimicrobial activity of these dendrimers is investigated and tested against five human pathogenic Gram‐positive and Gram‐negative bacteria, and minimum inhibitory concentrations are reported. Some of these synthesized dendrimers exhibit higher inhibitory activity against methicillin‐resistant Staphylococcus aureus, vancomycin‐resistant Enterococcus faecium, and Staphylococcus warneri compare to the reference drugs. As well, the in vitro and in vivo anti‐inflammatory activities of these dendrimers are evaluated. The results of in vivo anti‐inflammatory activity and histopathology of inflamed paws show that all dendrimers display considerable anti‐inflammatory activity; however, second‐generation dendrimer ( G2‐D6 ) shows the best anti‐inflammatory activity, which is more potent than the commercial drug ibuprofen at the same tested dose. Results of the toxicity study reveal that G2‐D6  is the safest drug on biological tissues.     

New Pyrazolyl‐Nicotinic Acids,Methyl Esters,and 1,3,4‐Oxadiazolyl‐pyrazolyl‐pyridine Tricyclic Scaffold Derivatives from 6‐Hydrazinylnicotinic Acid Hydrazide Hydrate

This paper describes an efficient approach for the synthesis of a new series of 6‐[3‐alkyl(aryl/heteroaryl)‐5‐trifluoromethyl‐1H‐pyrazol‐1‐yl]nicotinic acids (where alkyl = CH₃; aryl = Ph, 4‐OCH₃Ph, 4,4′‐BiPh; and heteroaryl = 2‐Furyl) from the hydrolysis reaction of alkyl(aryl/heteroaryl)substituted 2‐(5‐trifluoromethyl‐5‐hydroxy‐4,5‐dihydro‐1H‐pyrazol‐1‐yl)‐5‐(5‐trifluoromethyl‐5‐hydroxy‐4,5‐dihydro‐1H‐1‐carbonylpyrazol‐1‐yl)pyridines, under basic conditions and at 70–95% yields. In a subsequent step, the esterification reaction of pyrazolyl‐nicotinic acids done in thionyl chloride and methanol led to the isolation of a series of methyl 6‐[alkyl(aryl/heteroaryl)‐5‐trifluoromethyl‐1H‐pyrazol‐1‐yl] nicotinates as stable hydrochloride salts at 64–84% yields, which could be easily converted to hydrazides to give new oxadiazolyl‐pyrazolyl‐pyridine tricyclic scaffolds at good yields from a [4 + 1] cyclocondensation reaction with 1,1,1‐triethoxyethane and 1‐(triethoxymethyl)benzene as the reagent/solvent.     

Synthesis and Antiproliferative Activity of 6‐Ferrocenyl‐3‐Substituted 7H‐1,2,4‐Triazolo[3, 4‐b]‐1,3,4‐Thiadiazines

Five new 6‐ferrocenyl‐3‐substituted 7H‐1,2,4‐triazolo[3, 4‐b]‐1,3,4‐thiadiazines ( 3a‐e ) have been synthesized and characterized on the basis of elemental analyses and spectral data. The antiproliferative activities were examined in two human cell lines (BJ and HT 1080) with the acid phosphatase assay. The results showed that all compounds could reduce cell viability. The significant difference between the two cell lines was that fibrosarcoma HT 1080 cells could indeed be more susceptible to the compounds than the normal fibroblast BJ cells.     

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 and In Vivo Anticonvulsant Screening of Coumarin Incorporated Schiff Bases of 1,3,4‐Oxadiazoles

A series of coumarin incorporated Schiff bases of 1,3,4‐oxadiazoles ( 1‐18 ) was synthesized. The structures of the synthesized compounds were confirmed on the basis of spectral data and elemental analysis. The anticonvulsant and neurotoxicity was studied by maximal electroshock seizure (MES) and rotorod method, respectively. A majority of the compounds were active in MES test. All the compounds were less neurotoxic than the standard drug phenytoin.     

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.     

Synthesis of 3‐(Pyridin‐4‐Ylmethyl)‐4‐Substituted‐1,2,4‐Triazoline‐5‐Thione

The reaction of the hydrazide of pyridine‐4‐acetic acid with isothiocyanate gave thiosemicarbazide derivatives respectively. Further cyclization with 2% NaOH led to the formation of 4‐substituted 3‐(pyridin‐4‐ylmethyl)‐1,2,4‐triazoline‐5‐thione and 3‐(pyridin‐4‐ylmethyl)‐1,2,4‐triazoline‐5‐thione. The structures of all new products were confirmed by analytical and spectroscopic methods.     

Synthesis and Anti‐HIV Activity of Triazolo‐Fused 3′,5′‐Cyclic Nucleoside Analogues Derived from an Intramolecular Huisgen 1,3‐Dipolar Cycloaddition

Triazolo‐fused 3′,5′‐cyclic nucleoside analogues were synthesized by an intramolecular 1,3‐dipolar cycloaddition of nucleoside‐derived azido‐alkynes in a regio‐ and stereospecific manner. The thymine nucleoside base in these target compounds was transformed successfully into the corresponding 5‐methylcytosine component. The synthesized compounds were examined in a MAGI assay for exploring the anti‐HIV activity and in a H9 T lymphocytes assay for measuring the cell toxicity.     

Synthesis and Antimicrobial Activity of New 2,5‐Disubstituted 1,3,4‐Oxadiazoles and 1,2,4‐Triazoles and Their Sugar Derivatives

A series of new 2,5‐disubstituted‐1,3,4‐oxadiazole and 1,2,4‐triazole derivatives were synthesized by heterocyclization of acid hydrazide 1 and thiosemicarbazide derivative 2 . Furthermore, the acyclic C‐nucleoside analogs were prepared by cyclization of their corresponding sugar hydrazones by reaction with acetic anhydride. The antimicrobial activity of the prepared compounds was evaluated and some of the synthesized compounds revealed good activities against fungi.     

Synthesis of 1,2,3‐Triazole Analogues of Lincomycin

In search for new antibiotics we replaced the amide moiety of lincomycin 1 by a 1,2,3‐triazole ring. The 1,2,3‐triazoles 10a – 10k were obtained as single regioisomers by ‘click reaction’ of azide 5 with the alkyne 9k , derived from propyl hygric acid, and the alkyl, aryl, or cycloalkyl alkynes ribosomes 9a – 9j . The new analogues proved inactive towards wild‐type and A2058G mutant.