Antiproliferative and Antiprostate Cancer Activities of Heterocyclic Compounds Derived from Cyclohexane-1,4-dione.

2-Amino-6-oxo-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (3) was prepared from the reaction of cyclohexane-1,4-dione with elemental sulfur and malononitrile in 1,4-dioxane and triethylamine as catalyst. The latter compound reacted with triethyl orthoformate and either malononitrile or ethyl cyanoacetate in 1,4-dioxane in the presence of triethylamine to produce 4H-thieno[2,3-f]chromene derivatives 10a,b. In addition, fused pyran and pyridine derivatives were synthesized starting from compound 3.

Anti-proliferative, c-Met Inhibitions, and PAINS Evaluations of New Thiophene, Thiazole, Coumarin, Pyran, and Pyridine Derivatives.

Background: 1,3-Diones are versatile reagents used for many heterocyclic transformations. Among such groups of compounds, cyclohexane-1,3-dione is widely used in organic synthesis to produce biologically active compounds.

Objective: In this work, target molecules were synthesized from tetrahydrobenzo[b]thiophen-3- carboxamide derivative with different substituents, and their structure-activity relationships were discussed in detail.

Uses of cyclohexane-1,3-dione for the synthesis of 1,2,4-triazine derivatives as anti-proliferative agents and tyrosine kinases inhibitors.

Tetrahydrobenzo[b]thiophene derivatives were well known to be biologically active compounds and many of them occupy a wide range as anticancer agent drugs. One of our main aim of this work was to synthesize target molecules not only possess anti-tumor activities but also kinase inhibitors. To achieve this goal, our strategy was to synthesize a series of novel 1,2,4-triazines as efficient anticancer drugs with low cytotoxicity and good bioavailability properties using cyclohexane-1,3-dione and 3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophene-2-diazonium chloride to give the 2-(2-(2,6-dioxocyclohexylidene)hydrazinyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile (3) as the key starting material for many heterocyclization reactions.

Heterocyclization of 2-Arylidenecyclohexan-1,3-dione: Synthesis of Thiophene, Thiazole, and Isoxazole Derivatives with Potential Antitumor Activities.

Background: Thiophene, thiazole, and isoxazole derivatives are present in a wide range of natural and synthetic compounds with heterogeneous pharmacological activity. Due to their structural diversity, they are some of the most versatile classes of compounds for anticancer drug design and discovery.

Objective: Thiophene, thiazole, and isoxazole derivatives were herein designed with a dual purpose: as antiproliferative agents and kinase inhibitors.

New Approaches for the Uses of Cyclohexan-1,4-dione for the Synthesis of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-b]pyridine Derivatives used as Potential Anti-prostate Cancer Agents and Pim-1 Kinase Inhibitors.

Background: Among the wide range of heterocycles, tetrahydrobenzothienopyridine derivatives acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Many pharmacological drugs containing the thiophene nucleus were known in the market.

Method: A series of tetrahydrobenzothienopyridine derivatives were synthesized from the reaction of 2-amino- 3-benzoyl-4,5-dihydrobenzo[b]thiophen-6(7H)-one, synthesized and used for further heterocyclization reactions through reaction with different reagents.

Cytotoxicity and Anti-proliferative Properties of Heterocyclic Compounds Derived from Progesterone.

The following study explored the cytotoxic effect on human cancer cells of a series of novel progesterone derivatives through the synthesis of heterocyclic compounds incorporating progesterone moiety. The reaction of progesterone (1) with cyanoacetanilide derivatives gave the condensation products 3a,b. Either of compound 3a or 3b reacted with elemental sulfur affording the thiophene derivatives 4a and 4b, respectively.

Synthesis and Cytotoxic Evaluation of Pyran, Dihydropyridine and Thiophene Derivatives of 3-Acetylcoumarin.

A series of coumarin analogues bearing 4H-pyran rings 2a-d, 11a-d and 1,4-dihydropyridine rings 3a-d, 12a-d at position 3 were synthesized starting from either 3-acetyl coumarin (1) or the coumarin acetohydrazide derivative 4. Condensation of 3-acetylcoumarin (1) with 2-cyanoacetohydrazide afforded 2-cyano-N'-{1-[2-oxo-2H-chromen-3-yl]ethylidene}acetohydrazide (4). Reaction of compound 4 with elemental sulfur and either malononitrile or ethyl cyanoacetate afforded the thiophene derivatives 8 and 9, respectively.

Uses of 3-(2-Bromoacetyl)-2H-chromen-2-one in the Synthesis of Heterocyclic Compounds Incorporating Coumarin: Synthesis, Characterization and Cytotoxicity.

In this work, 3-bromoacetylcoumarin was used as the key starting material for the synthesis of pyran, pyridine, thiophene, thiazole and pyrazole derivatives through its reaction with different reagents. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses. All of the synthesized compounds were screened for their in vitro anticancer activity against six human cancer cell lines, namely: human gastric cancer (NUGC), human colon cancer (DLD1), human liver cancer (HA22T and HEPG2), nasopharyngeal carcinoma (HONE1), human breast cancer (MCF) and normal fibroblast cells (WI38).

Synthesis and anticancer evaluation of 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, 1,2,4-triazoles and Mannich bases.

A series of 5-(pyridin-4-yl)-N-substituted-1,3,4-oxadiazol-2-amines (3a-d), 5-(pyridin-4-yl)-N-substituted-1,3,4-thiadiazol-2-amines (4a-d) and 5-(pyridin-4-yl)-4-substituted-1,2,4-triazole-3-thiones (5a-d) were obtained by the cyclization of hydrazinecarbothioamide derivatives 2a-d derived from isonicotinic acid hydrazide. Aminoalkylation of compounds 5a-d with formaldehyde and various secondary amines furnished the Mannich bases 6a-p. The structures of the newly synthesized compounds were confirmed on the basis of their spectral data and elemental analyses.

Synthesis and antitumor evaluation of novel dihydropyrimidine, thiazolo[3,2-a]pyrimidine and pyrano[2,3-d]pyrimidine derivatives.

A simple and efficient method has been developed for the synthesis of 4,5-dihydro-2-mercapto-4-oxo-6-substituted arylpyrimidine derivatives (2a-e) and their fused rings (3b, 4b, 5b & 6b) and also 1,4-dihydro-2-mercaptopyrimidine derivatives (7a-e) & (9a-e) using triethylamine as a catalyst. The structure of the newly synthesized compounds was confirmed on the basis of their spectral data and elemental analysis. All the synthesized compounds were evaluated for their in vitro anticancer activity against six human cancer cell lines and normal fibroblasts.

Synthesis of novel 1,2,4-triazoles, triazolothiadiazines and triazolothiadiazoles as potential anticancer agents.

A series of new N-substituted-3-mercapto-1,2,4-triazoles (3a,b and 7a-d), triazolo[1,3,4]thiadiazines (5a,b) and triazolo[1,3,4]thiadiazoles (4a-d, 6 and 8a-d) have been synthesized starting from isonicotinic acid hydrazide. The structure of the newly synthesized compounds was confirmed on the basis of their spectral data and elemental analyses. All the compounds were screened for their in vitro anticancer activity against 6 human cancer cell lines and normal fibroblasts.