5-Thioxoimidazolidine-2-one derivatives: Synthesis, anti-inflammatory activity, analgesic activity, COX inhibition assay and molecular modelling study.

A series of 5-imino-4-thioxo-2-imidazolidinone derivatives with different substituents at N1 and N3 was synthesized with high yield and excellent purity by the reaction of different N-arylcyanothioformamide derivatives with isocyanate derivatives. Treatment 5-imino-4-thioxo-2-imidazolidinone derivatives with acidic medium afforded 4-thioxoimidazolidin-2,5-dione derivatives. The structures of the obtained products were established based on spectroscopic IR, 1H NMR, 13C NMR, 1H, 1H-COSY, HSQC and elemental analyses. The anti-inflammatory activity of the synthesized compounds through the carrageenan-paw edema model as well as in vitro COX-1 and COX-2 inhibition assay were evaluated where most of the synthesized compounds showed significant anti-inflammatory activity. Mostly, all of our synthesized compounds have greater activity more than celecoxib toward both cyclooxygenase enzymes. All of the tested compounds (except one compound) exhibited IC50 valves for COX-2 ranged from 0.001 × 10-3 to 0.827 × 10-3 µM while the reference drug has IC50 40.0 × 10-3 µM. Furthermore, the analgesic activity of such compounds was also determined. Molecular modeling study was also conducted to rationalize the potential as anti-inflammatory agents of our synthesized compounds by predicting their binding modes, binding affinities and optimal orientation at the active site of the COX enzymes.

Design, synthesis, anti-inflammatory antitumor activities, molecular modeling and molecular dynamics simulations of potential naprosyn® analogs as COX-1 and/or COX-2 inhibitors.

Inflammation is a fundamental physiological process that is essential for survival of human being but at the same time is one of the major causes of human morbidity and mortality. In the past decade, numerous advances have taken place in the understanding and development of novel anti-inflammatory drugs. Therefore, investigation of newest anti-inflammatory agents is still a major challenge. In this study, novel and successfully synthesized naproxen-derivatives indicated powerful anti-inflammatory properties as potent of COX-1 and/or COX-2 inhibitors are reported. Results obtained revealed the presence of very potent derivatives with% inhibition of the oedema by 100% in addition to enzyme inhibition values that can reach 92%. The molecular docking and molecular dynamic calculations have been studied. Thus, new potent candidates for further investigation as prospective non-steroidal anti-inflammatory drug were proposed. Furthermore, twenty of the synthesized derivatives have been selected by the NCI, USA for anti-cancer screening and some of the tested compounds showed good% growth inhibition and some selectivity against some cell lines such as melanoma, non-small cell lung and colon cancer with GI% values ranging from 60.9 to 82.8%. Structure activity relationship has been performed and molecular modeling studies and molecular dynamic simulations have been performed for more explanation of the action of the synthesized compounds.

2-Amino-4-(4-chloro-phen-yl)-4H-chromeno[8,7-b]pyridine-3-carbonitrile.

The asymmetric unit of the title compound, C19H12ClN3O, contains two mol-ecules with similar conformations. The 14 non-H atoms comprising the 4H-chromeno[8,7-b]pyridine residue are essentially coplanar (r.m.s. deviations = 0.037 and 0.042 Šfor the two mol-ecules) and the main difference between them is seen in the twist about the bond linking the main residue to the attached chloro-benzene rings [dihedral angles = 79.01 (12) and 76.22 (11)° for the two mol-ecules]. Zigzag supra-molecular chains along the a-axis direction mediated by amino-pyridine N-H⋯N hydrogen bonds feature in the crystal packing; these are connected into a three-dimensional architecture by C-H⋯π inter-actions and Cl⋯Cl contacts [Cl⋯Cl = 3.3896 (14) Å].

Synthesis of 4H-chromene, coumarin, 12H-chromeno[2,3-d]pyrimidine derivatives and some of their antimicrobial and cytotoxicity activities.

Condensation of 3-N,N-diethylaminophenol (1) with α-cyanocinnamonitriles (2a-c) and ethyl α-cyanocinnamates (2d-f) provided compounds 3a-f and 4a-c. 12H-Chromeno[2,3-d]pyrimidine derivatives 6, 11-13 and 16 were obtained by treatment of 4H-chromene compounds (3) with different electrophiles followed by nucleophilic reagents. Structures of these compounds were established on the basis of IR, UV, 1H NMR, 13C NMR and MS data. Some of the new compounds were evaluated for antimicrobial and cytotoxicity activities.

Analgesic, anticonvulsant and anti-inflammatory activities of some synthesized benzodiazipine, triazolopyrimidine and bis-imide derivatives.

A series of diazipine, pyrimidine, fused triazolopyrimidine and imide derivatives were newly synthesized using 4-phenyl-but-3-en-2-one 1 as a starting material and compounds 2 and 9 are intermediates. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All the compounds were interestingly less toxic than the reference drug. The pharmacological screening showed that many of these obtained compounds have good analgesic, anticonvulsant and anti-inflammatory activities comparable to Valdecoxib, Carbamazepine and Predensilone as reference drugs. Regarding the protection against Carrageenan induced edema, five compounds were found more potent than Prednisolone. On the other hand, in searching for COX-2 inhibitor, the inhibition of plasma PGE2 for the compounds were determined and four compounds were found more potent than Prednisolone. The detailed synthesis, spectroscopic data, pharmacological screening and acute toxicity LD(50) for the synthesized compounds were reported.

Anti-inflammatory and analgesic activities of newly synthesized chiral peptide derivatives using (3-benzoyl- 4,5-dioxo-2-phenyl-pyrrolidin-1-yl)acetic acid ethyl ester as starting material.

A series of heterocyclic derivatives was synthesized using (3-benzoyl-4,5-dioxo-2-phenyl-pyrrolidin-1-yl)acetic acid ethyl ester 1 as starting material. Treatment of 1 with 1 N NaOH or hydrazine hydrate afford the corresponding acid 2 and acid hydrazides 4 and 5, which were reacted with several reagents to produce some new peptido hetero-organic derivatives 6-12. The pharmacological screening showed that many of these newly synthesized compounds have good anti-inflammatory and analgesic activities comparable to diclofenac potassium and valdecoxib as reference drugs.

Synthesis and biological evaluation of new 3-substituted indole derivatives as potential anti-inflammatory and analgesic agents.

Treatment of 3-cyanoacetyl indole 1 with the diazonium salts of 3-phenyl-5-aminopyrazole and 2-aminobenzimidazole afforded the corresponding hydrazones 4 and 5. 3-Cyanoacetyl indole reacted with phenylisothiocyanate to give the corresponding thioacetanilide derivative 7. Treatment of 7 with hydrazonoyl chlorides afforded the corresponding 1,3,4-thiadiazole derivatives 8a-f and 9. Also, the thioacetanilide reacted with alpha-haloketones to afford thiophene derivatives 10a,b (tenidap analogues), or thiazolidin-4-one derivative 11. The newly synthesized compounds were found to possess potential anti-inflammatory and analgesic activities.