Thiazolo[3,2-a][1,3]diazepine derivatives and pharmaceutical compositions containing the same as ... more Thiazolo[3,2-a][1,3]diazepine derivatives and pharmaceutical compositions containing the same as novel anticonvulsant agents and method for their preparation.
New series of 1,3,4-thiadiazoles have been prepared via reaction of 1,3,4-thiadiazolenaminones 1 ... more New series of 1,3,4-thiadiazoles have been prepared via reaction of 1,3,4-thiadiazolenaminones 1 with N-phenyl 2-oxopropanehydrazonoyl chloride (2) in dioxane in the presence of triethylamine. Also, some new heterocycles incorporating 1,3,4-thiadiazole ring were obtained by reaction of 1,3,4-thiadiazolenaminones 1 with nitrogen-nucleophiles like hydrazine hydrate, 3-amino-1,2,4-triazole and 2-aminobenzimidazole. The structure of the new products was established based on elemental and spectral analysis. The relation between the structure of the products and their activity towards some microorganisms was studied and promising results were obtained.
Lead derivatives of 2-cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazineca... more Lead derivatives of 2-cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides 1-18 were synthesized, characterized and evaluated in vitro against HER-2 overexpressed breast cancer cell line SKBr-3. All the compounds showed activity against HER-2 overexpressed SKBr-3 cells with IC50 = 17.44 ± 0.01 µM to 53.29 ± 0.33 µM. (2Z)-2-(3-Hydroxybenzylidene)-N-(3-methoxyphenyl)hydrazinecarbothioamide (12, IC50 = 17.44 ± 0.01 µM) was found to be most potent compound of this series targeting HER-2 overexpressed breast cancer cells compared to the standard drug 5-fluorouracil (5-FU) (IC50 = 38.58 ± 0.04 µM). Compound 12 inhibited the cellular proliferation via DNA degradation.
A series of new 3-substituted-7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methylpy... more A series of new 3-substituted-7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methylpyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4(3H)-one derivatives were synthesized as antimicrobial agents using 7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methyl-4H-pyrido[3',2':4,5]thieno[3,2-d]-[1,3]oxazin-4-one as a starting compound. Its condensation with substituted aniline derivatives or phenyl hydrazine gave the corresponding N-substituted derivatives. Treatment of the starting compound with hydrazine hydrate afforded the corresponding N-amino derivative, which was reacted with substituted phenylisocyanate and phenylisothiocyanate derivatives to give the corresponding semicarbazides and thiosemicarbazide derivatives. All the newly synthesized compounds were evaluated for their antimicrobial activities in comparison to streptomycin and fusidic acid as positive controls. The structure assignments of the new compounds are based on chemical and spectroscopic...
A series of pyridines, pyrimidinones, oxazinones and their derivatives were synthesized as antimi... more A series of pyridines, pyrimidinones, oxazinones and their derivatives were synthesized as antimicrobial agents using citrazinic acid (2,6-dihydroxyisonicotinic acid) as a starting material. α,β-Unsaturated ketones 3a-c were condensed with cyanothio-acetamide in the presence of ammonium acetate to give 2-cyanopyridinethiones 4a-c, which were reacted with ethyl chloroacetate to yield the corresponding cyano esters 5a-c. The esters 5a-c were cyclized by action of sodium methoxide to aminoesters 6a-c, which were aminolyzed with ammonia to corresponding aminoamide derivatives 7a-c. Also, the esters 6a-c were hydrolyzed with NaOH to the corresponding sodium salt 8a-c, which were treated with acetic anhydride to afford 2-methyloxazinones 9a-c. The latter compounds were treated with ammonium acetate to afford 2-methylpyrimidinones 10a-c, followed by methylation with methyl iodide to yield 2,3-dimethyl-pyrimidinones 11a-c. The antimicrobial screening showed that many of these compounds have...
N-aryl phthalimides (1-10P) derived from thalidomide by insertion of hydrophobic groups were eval... more N-aryl phthalimides (1-10P) derived from thalidomide by insertion of hydrophobic groups were evaluated for anti-inflammatory activity and one compound (4-(1,3-dioxo-1,3-dihydro-2H- isoindol-2-yl)-N'-[(4-ethoxyphenyl)methylidene]benzohydrazide (6P)) was identified as a promising anti-inflammatory agent. Further testing confirmed that compared with the control, 6P treatment resulted in a considerable decrease in CD4+, NF-κB p65+, TNF-α+, IL-6+, GITR+ and IL-17+ cell populations and an increase in the Foxp3+, CD4+Foxp3+ and IκBα+ populations in whole blood and pleural fluid of a mouse model of lung inflammation. Moreover, treatment with the 6P compound decreased proteins associated with inflammation including TNF-α, IL-6, IL- 17, GITR, NF-κB, COX-2, STAT-3, and iNOS while increasing anti-inflammatory mediators such as IL-10 and IL-4. Histopathological examination confirmed the potent anti-inflammatory effects of the 6P compound. Thus, the phthalimide derivative 6P acts as a potent ...
A series of dihydrobenzo[h]quinazoline derivatives 5–19 were synthesized using arylmethylene 2, t... more A series of dihydrobenzo[h]quinazoline derivatives 5–19 were synthesized using arylmethylene 2, thiopyrimidine 3 and 2-(4-(thiophen-2-yl)-5,6-dihydrobenzo[h]quinazolin-2-ylthio) acetic acid (4) as a starting materials. The biological screening showed that many of these compounds have good anticancer and antiviral activities. The structure assignments of the new compounds based on chemical and spectroscopic evidence. The detailed synthesis, spectroscopic data, and pharmacological properties are reported. Keywords. Arylmethylene; thiopyrimidine; dihydrobenzo[h]quinazolin-2-ylthioacetic acid; anticancer; antiviral and cytotoxic evaluations.
Some novel bicyclic thiazolopyrimidine derivatives bearing various substituents have been synthes... more Some novel bicyclic thiazolopyrimidine derivatives bearing various substituents have been synthesized through one-pot three-component method. Structures of the target compounds were confirmed by elemental analysis and spectral data. Some selected members of the newly synthesized compounds were investigated for their analgesic and anti-inflammatory activities and revealed pronounced anti-inflammatory activity greater than that of indomethacin (reference drug).
The terpenoidal oxaliplatin derivatives 6 and 12 were synthesized previously using 2β,3α-di-hydro... more The terpenoidal oxaliplatin derivatives 6 and 12 were synthesized previously using 2β,3α-di-hydroxy-11-oxo-18β-olean-12-ene-30-oic acid (1) and 2α,2β-dihydroxy-18β-ursan-12-ene-28-oic acid (7) as starting materials. Also, some of the previously synthesized compounds exhibited better cytotoxicity and antioxidant activities than Oxaliplatin® and vitamin C as positive controls. Herein, these compounds were evaluated for their anti-alzheimer activities and were compared to Fluriprofen® as positive control. The detailed pharmacological screening and acute toxicity (LD 50) for these compounds were reported.
The reaction of 5-(1-adamantyl)-4-substituted-1,2,4-triazoline-3-thione 5a,b and 10a,b with forma... more The reaction of 5-(1-adamantyl)-4-substituted-1,2,4-triazoline-3-thione 5a,b and 10a,b with formaldehyde solution and various primary aromatic amines or 1-substituted piperazines yielded the corresponding N-Mannich bases 6a-o, 7a-g and 11a-i. The newly synthesized N-Mannich bases 6a-o, 7a-g and 11a-i were tested for in vitro inhibitory activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. The compounds 6j, 6l, 6m, 7a, 7b, 7c, 7d, 7f, 11a, 11b, 11c, 11d, 11e, 11f, 11h and 11i displayed moderate to good activity against the tested Gram-positive bacteria, while compounds 7c, 11c, 11d, 11f and 11h showed potent broad spectrum antibacterial activity. None of the newly synthesized compounds were proved to possess marked activity against C. albicans.
Thiazolo[3,2-a][1,3]diazepine derivatives and pharmaceutical compositions containing the same as ... more Thiazolo[3,2-a][1,3]diazepine derivatives and pharmaceutical compositions containing the same as novel anticonvulsant agents and method for their preparation.
New series of 1,3,4-thiadiazoles have been prepared via reaction of 1,3,4-thiadiazolenaminones 1 ... more New series of 1,3,4-thiadiazoles have been prepared via reaction of 1,3,4-thiadiazolenaminones 1 with N-phenyl 2-oxopropanehydrazonoyl chloride (2) in dioxane in the presence of triethylamine. Also, some new heterocycles incorporating 1,3,4-thiadiazole ring were obtained by reaction of 1,3,4-thiadiazolenaminones 1 with nitrogen-nucleophiles like hydrazine hydrate, 3-amino-1,2,4-triazole and 2-aminobenzimidazole. The structure of the new products was established based on elemental and spectral analysis. The relation between the structure of the products and their activity towards some microorganisms was studied and promising results were obtained.
Lead derivatives of 2-cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazineca... more Lead derivatives of 2-cyclohexyl-N-[(Z)-(3-methoxyphenyl/3-hydroxyphenyl) methylidene]hydrazinecarbothioamides 1-18 were synthesized, characterized and evaluated in vitro against HER-2 overexpressed breast cancer cell line SKBr-3. All the compounds showed activity against HER-2 overexpressed SKBr-3 cells with IC50 = 17.44 ± 0.01 µM to 53.29 ± 0.33 µM. (2Z)-2-(3-Hydroxybenzylidene)-N-(3-methoxyphenyl)hydrazinecarbothioamide (12, IC50 = 17.44 ± 0.01 µM) was found to be most potent compound of this series targeting HER-2 overexpressed breast cancer cells compared to the standard drug 5-fluorouracil (5-FU) (IC50 = 38.58 ± 0.04 µM). Compound 12 inhibited the cellular proliferation via DNA degradation.
A series of new 3-substituted-7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methylpy... more A series of new 3-substituted-7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methylpyrido[3',2':4,5]thieno[3,2-d]pyrimidin-4(3H)-one derivatives were synthesized as antimicrobial agents using 7-(2-chloro-6-ethoxypyridin-4-yl)-9-(2,4-dichlorophenyl)-2-methyl-4H-pyrido[3',2':4,5]thieno[3,2-d]-[1,3]oxazin-4-one as a starting compound. Its condensation with substituted aniline derivatives or phenyl hydrazine gave the corresponding N-substituted derivatives. Treatment of the starting compound with hydrazine hydrate afforded the corresponding N-amino derivative, which was reacted with substituted phenylisocyanate and phenylisothiocyanate derivatives to give the corresponding semicarbazides and thiosemicarbazide derivatives. All the newly synthesized compounds were evaluated for their antimicrobial activities in comparison to streptomycin and fusidic acid as positive controls. The structure assignments of the new compounds are based on chemical and spectroscopic...
A series of pyridines, pyrimidinones, oxazinones and their derivatives were synthesized as antimi... more A series of pyridines, pyrimidinones, oxazinones and their derivatives were synthesized as antimicrobial agents using citrazinic acid (2,6-dihydroxyisonicotinic acid) as a starting material. α,β-Unsaturated ketones 3a-c were condensed with cyanothio-acetamide in the presence of ammonium acetate to give 2-cyanopyridinethiones 4a-c, which were reacted with ethyl chloroacetate to yield the corresponding cyano esters 5a-c. The esters 5a-c were cyclized by action of sodium methoxide to aminoesters 6a-c, which were aminolyzed with ammonia to corresponding aminoamide derivatives 7a-c. Also, the esters 6a-c were hydrolyzed with NaOH to the corresponding sodium salt 8a-c, which were treated with acetic anhydride to afford 2-methyloxazinones 9a-c. The latter compounds were treated with ammonium acetate to afford 2-methylpyrimidinones 10a-c, followed by methylation with methyl iodide to yield 2,3-dimethyl-pyrimidinones 11a-c. The antimicrobial screening showed that many of these compounds have...
N-aryl phthalimides (1-10P) derived from thalidomide by insertion of hydrophobic groups were eval... more N-aryl phthalimides (1-10P) derived from thalidomide by insertion of hydrophobic groups were evaluated for anti-inflammatory activity and one compound (4-(1,3-dioxo-1,3-dihydro-2H- isoindol-2-yl)-N'-[(4-ethoxyphenyl)methylidene]benzohydrazide (6P)) was identified as a promising anti-inflammatory agent. Further testing confirmed that compared with the control, 6P treatment resulted in a considerable decrease in CD4+, NF-κB p65+, TNF-α+, IL-6+, GITR+ and IL-17+ cell populations and an increase in the Foxp3+, CD4+Foxp3+ and IκBα+ populations in whole blood and pleural fluid of a mouse model of lung inflammation. Moreover, treatment with the 6P compound decreased proteins associated with inflammation including TNF-α, IL-6, IL- 17, GITR, NF-κB, COX-2, STAT-3, and iNOS while increasing anti-inflammatory mediators such as IL-10 and IL-4. Histopathological examination confirmed the potent anti-inflammatory effects of the 6P compound. Thus, the phthalimide derivative 6P acts as a potent ...
A series of dihydrobenzo[h]quinazoline derivatives 5–19 were synthesized using arylmethylene 2, t... more A series of dihydrobenzo[h]quinazoline derivatives 5–19 were synthesized using arylmethylene 2, thiopyrimidine 3 and 2-(4-(thiophen-2-yl)-5,6-dihydrobenzo[h]quinazolin-2-ylthio) acetic acid (4) as a starting materials. The biological screening showed that many of these compounds have good anticancer and antiviral activities. The structure assignments of the new compounds based on chemical and spectroscopic evidence. The detailed synthesis, spectroscopic data, and pharmacological properties are reported. Keywords. Arylmethylene; thiopyrimidine; dihydrobenzo[h]quinazolin-2-ylthioacetic acid; anticancer; antiviral and cytotoxic evaluations.
Some novel bicyclic thiazolopyrimidine derivatives bearing various substituents have been synthes... more Some novel bicyclic thiazolopyrimidine derivatives bearing various substituents have been synthesized through one-pot three-component method. Structures of the target compounds were confirmed by elemental analysis and spectral data. Some selected members of the newly synthesized compounds were investigated for their analgesic and anti-inflammatory activities and revealed pronounced anti-inflammatory activity greater than that of indomethacin (reference drug).
The terpenoidal oxaliplatin derivatives 6 and 12 were synthesized previously using 2β,3α-di-hydro... more The terpenoidal oxaliplatin derivatives 6 and 12 were synthesized previously using 2β,3α-di-hydroxy-11-oxo-18β-olean-12-ene-30-oic acid (1) and 2α,2β-dihydroxy-18β-ursan-12-ene-28-oic acid (7) as starting materials. Also, some of the previously synthesized compounds exhibited better cytotoxicity and antioxidant activities than Oxaliplatin® and vitamin C as positive controls. Herein, these compounds were evaluated for their anti-alzheimer activities and were compared to Fluriprofen® as positive control. The detailed pharmacological screening and acute toxicity (LD 50) for these compounds were reported.
The reaction of 5-(1-adamantyl)-4-substituted-1,2,4-triazoline-3-thione 5a,b and 10a,b with forma... more The reaction of 5-(1-adamantyl)-4-substituted-1,2,4-triazoline-3-thione 5a,b and 10a,b with formaldehyde solution and various primary aromatic amines or 1-substituted piperazines yielded the corresponding N-Mannich bases 6a-o, 7a-g and 11a-i. The newly synthesized N-Mannich bases 6a-o, 7a-g and 11a-i were tested for in vitro inhibitory activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. The compounds 6j, 6l, 6m, 7a, 7b, 7c, 7d, 7f, 11a, 11b, 11c, 11d, 11e, 11f, 11h and 11i displayed moderate to good activity against the tested Gram-positive bacteria, while compounds 7c, 11c, 11d, 11f and 11h showed potent broad spectrum antibacterial activity. None of the newly synthesized compounds were proved to possess marked activity against C. albicans.
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Papers by Mohamed Al-omar