Synthesis of substituted pyrimido[4,5‐b] and [5,4‐c]‐[1,8]naphthyridines

Ethyl 1‐ethyl‐7‐methyl‐4‐oxo‐1,4‐dihydro[1,8]naphthyridine‐3‐carboxylate ( 1 ), precursor of nalidixic acid, has been converted in two steps through ([1,8]naphthyridin‐3‐yl)carbonylguanidine derivatives into substituted pyrimido[4,5‐b] and [5,4‐c][1,8]naphthyridines.     

Synthesis of new 4,5,6,7‐tetrahydro‐3H‐imidazo[4,5‐c]pyridine derivatives

The synthesis of new ligands for the H₃ histamine receptor is described. These new compounds are spinacine derivatives obtained by alkylation or Michael reaction at C6 position.     

Oxidative cyclization of n‐methyl‐ and n‐benzoylpyridylthioureas. Preparation of new thiazolo[4,5‐b] and [5,4‐b] pyridine derivatives

Cyclization of N‐methyl‐ and N‐benzoylpyridylthioureas, prepared from the corresponding aminopy‐ridines, has been realized using various conditions. With bromine in acetic acid or potassium ferricyanide, the cyclization occurred on the nitrogen of the pyridine ring and pyridinium salts or 1,2,4‐fhiadiazolo[2,3‐a]pyridylidene systems were obtained. On the other hand, treatment of the thioureas with sodium methoxide in N‐methylpyrrolidinone (NMP) led to formation of fhiazolo[4,5‐b] and [5,4‐b]pyridines, which are interesting targets for biological evaluation.     

Design,Synthesis, and Fungicidal Activity of Novel Imidazo[4,5‐b]pyridine Derivatives

A series of novel imidazo[4,5‐b]pyridine derivatives were designed and synthesized. The structures of all the newly synthesized compounds were identified by spectroscopic data NMR, MS, and elemental analysis. Bioassay showed that the compounds exhibited potent fungicidal activities against Erysiphe graminis, Puccinia polysora, and so forth. Particularly, 2‐chloro‐5‐((5‐methoxy‐2‐(2‐(trifluoromethyl)phenyl)‐3H‐imidazo[4,5‐b]pyridin‐3‐yl)methyl)thiazole ( 9b ) displayed fungicidal potency against P. polysora. Its EC₅₀ value: 4.00 mg/L is comparable with that of tebuconazole. The structure–activity relationship for the target compounds is discussed.     

Synthesis and mutagenic potency of structural isomers of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine

Synthesis of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), three structural isomers, and two desphenyl PhIP congeners has been carried out. Mutagenic potency was evaluated using S. typhimurium strain TA98 in the Ames test. Mutagenic potency increased in relation to structural features in these heterocyclic amines that allow extended resonance between the phenyl and imidazo[4,5‐b]pyridine N²‐amino substituents. By contrast, PhIP isomers, whose substitution disallows involvement of the phenyl group in their aminoimidazo resonance hybrids, and desphenyl congeners were from 86‐ to 234‐fold less mutagenic than PhIP.     

Synthesis and antitumor evaluation of some new derivatives and fused heterocyclic compounds derived from thieno[2,3‐b]pyridine

On the basis of the proven activity of thieno[2,3‐b]pyridines as anticancer, we have designed to synthesize a novel several heterocyclic compounds utilizing thieno[2,3‐b]pyridine as a skeleton through various chemical reactions. The synthesized compounds bear rings that are either directly attached to the thieno[2,3‐b]pyridine as in compounds 4 to 6 and 9 or connected through an amide bridge as compounds 2 , 3a ‐ b , 7 , and 8 . As well as, compounds 10 , 12 to 28 , 30 , 31 , and 33 to 36 bear fused rings to the thieno[2,3‐b]pyridine backbone. The newly synthesized compounds were screened for their antiproliferative activity in vitro against hepatocellular carcinoma (HepG‐2) and breast cancer (MCF‐7) compared with the standard drug (doxorubicin). Compounds 3b , 4 , 6 , 22 , and 28 exhibited promising growth inhibitory effect toward both HepG‐2 and MCF‐7 cell lines with IC₅₀ values ranging from 5.88 to 11.70 μg/mL and 9.64 to 15.10 μg/mL, respectively.     

Synthesis and antituberculotic activity of some new imidazo[4,5-b]pyridine derivatives

The reactions of 2-acetylimidazo[4,5-b]pyridine hydrazone with some alkyl-and arylisothiocyanates and some orthoesters were carried out. Various new derivatives of the titled compound such as thiosemicarbazones, ethoxymethylenehydrazones, and derivatives of the new pyrido-[3′,2′:4,5]imidazo[1,2-d][1,2,4]triazine ring system were obtained. Biological data for selected compounds are presented. Published in Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1571–1579, October, 2006.     

Synthesis and chemiluminescent activity of 8,9‐dihydrobenzo[g] pyridazino[4,5‐b]indole‐7,10(11H)‐diones

Substituted and unsubstituted naphthylamines were transformed into the corresponding triazole derivatives, which were converted to dimethyl 1H‐benz[g]indole‐2,3‐dicarboxylates by photocyclization. The reaction of the diesters with hydrazine hydrate gave the corresponding 8,9‐dihydrobenzo[g]‐pyridazino[4,5‐b]indole‐7,10(11H)‐diones (5) . One of compounds 5 was found to have chemiluminescent activity similar to luminol.     

Syntheses of oxazolo[4,5‐c]pyridine and 6‐azaindole

The preparation of oxazolo[4,5‐c]pyridine and 6‐azaindole from 4‐bromo‐3‐pivaloylaminopyridine ( 8 ) is reported. The oxazolopyridine 2‐tert‐butyl‐oxazolo[4,5‐c]pyridine ( 9 ) was successfully prepared from 8 in 78% yield by a new base/TBAB promoted non‐catalyzed microwave cyclisation strategy (10 min) or, alternatively, in 54% yield by conventional heating (48 hrs) and CuI catalysis. The 6‐azaindole 2‐phenyl‐1‐(trimethylacetyl)‐6‐azaindole ( 13 ) was prepared from 8 in a two step procedure, including a Sonogashira coupling reaction.     

Reactions with dimethylformamide‐dimethylacetal: Synthesis and reactions of several new pyridine and pyrazolo[3,4‐b]pyridine derivatives

6‐Aminopyridine‐2(1H)‐thiones 1a,b reacted with dimethylformamide‐dimethylacetal (DMF‐DMA) to give the corresponding 6‐{[(N,N‐dimethylamino)methylene]amino}pyridine derivatives 2a,b . The latter compounds reacted with hydrazine hydrate to afford the 3,6‐diamino‐1H‐pyrazolo[3,4‐b]pyridine derivative 4 and 3‐amino‐5‐hydrazino‐1H‐pyrazolo[4′,3′:5,6]pyrido[2,3‐d]pyrimidine derivative 7 , respectively. Compound 4 condensed with DMF‐DMA to yield the 3,6‐bis{[(N,N‐dimethylamino)methylene]amino}‐1H‐pyrazolo[3,4‐b]pyridine derivative 10 , which reacted with malononitrile to give the corresponding pyridopyrazolopyrimidine derivative 15 . © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:399–404, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20312     

Synthesis of new derivatives of thieno[2,3‐b]pyridine fused with octyl ring

Derivatives of thiophene, thieno[2,3‐b]pyridine, thieno[5′,4′:4,5]pyrimido[3,2‐a]pyridine and thiepine fused with octyl ring have been synthesized and tested for antimicrobial and antifungal activities. The structure of the newly synthesized compounds have been established on the basis of their analytical and spectral data.     

One‐pot Synthesis of Benzo[4,5]imidazo[1,2‐a]pyridine Derivatives in Aqueous Conditions

One‐pot reaction of cyclic 1,3‐diketones, dimethylformamide dimethylacetal (DMFDMA) and 2‐(1H‐benzo[d ]imidaz‐2‐yl)acetonitrile was found to be a highly selective process leading to 4‐oxo‐1,2,3,4‐tetrahydrobenzo[4,5]imidazo[1,2‐a ]quinolin‐6‐yl cyanides. Optimized reaction conditions using water as solvent at room temperature or under microwave heating allowed high yields of the target products required no additional purification.     

A Convenient One‐Pot Synthesis of Thieno[2′,3′:4,5]Pyrimido[1,2‐b]‐[1,2,4,5]Tetrazines

A novel series of thieno[2′,3′:4,5]pyrimido[1,2‐b][1,2,4,5]tetrazin‐6‐one derivatives 14 were prepared from the reaction of 3‐amino‐2‐thioxo‐1,2,3,5,6,7‐hexahydro‐4H‐cyclopenta[4,5]thieno[2,3‐d]pyrimidin‐4‐one 3 or its methylthio 4 with hydrazonoyl chlorides 9 . The mechanism of the studied reactions has been discussed and further evidence for the assigned structure of the products is based on alternative synthesis. A single crystal X‐ray analysis of compound 14e has been carried out.     

Synthesis and Reactions of Naphtho[1′,2′:4,5]Furo[3,2‐b]Pyridine and Naphtho[1′,2′:4,5]Furo[3,2‐d]Pyrimidine Derivatives

2‐Acyl‐3‐aminonaphtho[2,1‐b]furan ( 1 ) reacts with activated methylene such as malono nitrile or ethyl cyanoacetate to afford naphtho[1′,2′:4,5]furo[3,2‐b]pyridine 2a,b . Chloroacylation of the amino group in compound ( 1 ) gave compound 3 which reacts with different amines to produce compound 4 .     

Design,Synthesis, Molecular Modeling Study,and Antimicrobial Activity of Some Novel Pyrano[2,3‐b]pyridine and Pyrrolo[2,3‐b]pyrano[2.3‐d]pyridine Derivatives

Novel derivatives of pyrano[2,3‐b]pyridine and pyrrolo[2,3‐b]pyrano[2.3‐d]pyridine were prepared, and their structures were elucidated by spectral and elemental analyses. The newly prepared candidates were evaluated for their antimicrobial activity against Candida sp., Aspergillus multi, Aspergillus niger, Escherichia coli, and Staphylococcus aureus. All the tested compounds revealed potent to moderate activity toward all tested microorganisms; especially, candidate 10 showed comparable antifungal activity as that showed by the standard drug ketoconazole toward Candida sp., and ethyl 4‐methyl‐1,7,8,9‐tetrahydropyrano[2,3‐b]pyrrolo[2,3‐d]pyridine‐3‐carboxylate ( 12 ) was the most active compound against all the tested bacteria. Furthermore, the newly synthesized compounds are subjected to molecular docking study for the inhibition of the enzyme L‐glutamine: D‐fructose‐6‐phosphate amidotransferase [GlcN‐6‐P], which is a new target for antimicrobials to explain action mode of these target compounds as leads for discovering other antimicrobial agents.     

A facile one‐pot synthesis of thiazo[2′,3′:2,1] imidazo[4,5‐b]pyrane; thiazo[2′,3′:2,1]imidazo [4,5,b]pyridine; imidazo[2,1‐b]thiazole and 2‐(2‐amino‐4‐methylthiazol‐5‐yl)‐1‐bromo‐1,2‐ethanedione‐1‐arylhydrazones

Thiazole 1 , when reacted with chloroacetyl chloride, afforded N‐(5‐acetyl‐4‐methylthiazol‐2‐yl) chloroacetamide 2 . It has been found that compound 2 reacted with α‐cyanocinnamonitrile derivatives 6a–c to afford reaction products 8a–c . Also, compound 2 coupled smoothly with benzenediazonium chloride afforded the phenylhydrazone 14 . Coupling of the sulfonium bromide 17 with diazotized aromatic amines or N‐nitrosoacetanilides afforded the arylhydrazones 20a,b . Treatment of 16 with 2‐cyanoethanethioamide afforded [4‐(2‐amino‐4‐methylthiazol‐5‐yl) thiazol‐2‐yl] acetonitrile 22 . © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:362–369, 2000     

Reactions of 6‐aminopyrimidines with 2‐dimethylaminomethylenetetralone. Regiospecific Synthesis Of 5,6‐Dihydrobenzo [h]pyrimido [4,5‐b] quinolines

Benzo[h]pyrimido[4,5‐b]quinolines ( 3 ) have been synthesized via a regiospecific cyclocondensation reaction between 6‐aminopyrimidines ( 1 ) and 2‐dimethylaminomethylentetralone hydrochloride ( 2 ). The linear structure of the final compounds were determined by nmr measurements, especially by ¹H,¹H, ¹H,¹³C COSY and DEPT experiments.     

Reactions with 3,6‐diaminothieno[2,3‐b]‐pyridines: Synthesis and characterization of several new fused pyridine heterocycles

6‐Aminopyridine‐2(1H)thiones 1 reacting with α‐halo‐compounds 2a–c afforded the alkylthiopyridine derivatives 3a–c which in turn cyclized to the corresponding thieno[2,3‐b]pyridine derivatives 4a–c . Several thieno[2,3‐b]pyridine derivatives 7, 16, 19 , pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidine derivatives 6a,b, 11a–c, 21 and pyrido[3′,2′:4,5]thieno[3,2‐c]pyridazine derivatives 13, 17 were prepared starting from compounds 4a–c . © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:405–413, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20313