Farid S. G. Soliman

Synthesis of new series of pyrazolo[4,3-d]pyrimidin-7-ones and pyrido[2,3-d]pyrimidin-4-ones for their bacterial and cyclin-dependent kinases (CDKs) inhibitory activities

Two series of pyrazolo[4,3-d]pyrimidin-7-ones and pyrido[2,3-d]pyrimidin-4-ones were designed, synthesised, and evaluated for their antibacterial activities and CDKs inhibitory activities. The pyridazine derivative: 6-phenyl-5-phenylhydrazono-2,3,4,5-tetrahydropyridazine-3,4-dione (3a) revealed activity against Staphylococcus aureus as Gram-positive bacteria while compound 2-(2-Ethoxyphenyl-5-Phenylpiperazinosulfonamido)-3H-pyrido[2,3-d]pyrimidin-4-one (13c) was showing moderate antifungal activity against Candida albicans.

Synthesis of some substituted furan-2(5H)-ones and derived quinoxalinones as potential anti-microbial and anti-cancer agents

In search for novel anti-cancer and anti-microbial agents with promising pharmacotoxicological profile, the synthesis of some substituted 4-halofuran-2(5H)-ones (8a–l, 9, 11) and derived halogenated quinoxalin-2(1H)-ones (12a–d) is described. Some of the halogenated furanones were readily oxidized to the corresponding 2-bromo-2-propenoic acids (13a–c) with hydrogen peroxide in alkaline medium. Twenty-two compounds were preliminary tested for their in vitro activity against three bacteria and one fungus and revealed encouraging activity. On the other hand, three compounds were screened as anti-cancer agents using cell line panel protocol and 22 compounds were subjected to cycline-dependent kinases (CDKs) inhibition screening program but were inactive.

Synthesis and 5-HT2A antagonist activity of derivatives of the novel heterocycles indolo[3,2-d]pyrrolo[3,2-g]azecine and benzo[d]pyrrolo[3,2-g]azecine compared to the benz[d]indolo[2,3-g]azecine derivative LE 300.

An indolo[3,2‐d]pyrrolo[3,2‐g]azecine and a benzo[d]pyrrolo[3,2‐g]azecine analogue of the potent dopamine receptor antagonist LE 300 (7‐methyl‐6,7,8,9,14,15‐hexahydro‐5H‐benz‐[d]indolo[2,3‐g]azecine) have been prepared in multi‐step reactions via C‐N bond cleavage of corresponding quaternary N‐methylquinolizinium iodides. LE 300, the target compounds and two precursor quinolizines have been tested in vitro for antagonist activity at 5‐HT2A receptors (rat tail artery) and H1 receptors (guinea‐pig ileum), respectively. LE 300 and compound 19 (3,6‐dimethyl‐ 4,5,6,7,8,13‐hexahydro‐3H‐benzo[d]pyrrolo[3,2‐g]azecine) competitively inhibited 5‐HT‐induced contractions with similar nanomolar potency (pA2 = 8.32 and 8.01, respectively) but were less active than the reference antagonist ketanserin (pA2 = 9.55). Compound 19 displayed moderate H1‐antihistaminic activity in the guinea‐pig ileum assay (pA2 = 7.37).

Benzimidazole condensed ring systems, III . Synthesis of some substituted 2,3-dihydrocyclopenta-1H-[4′,5′: 2,3]pyrido[1,2-a]benzimidazole-11-carbonitriles

SummaryThe synthesis of compound3 by condensing 1H-benzimidazole-2-acetonitrile (1) with ethyl cyclopentanone-2-carboxylate (2) in the presence of ammonium acetate is described. Methylation of3 with trimethyl phosphate yielded the N-methyl derivative4. Methods for converting3 to some of its related derivatives in which the carbonyl function was replaced by Cl, N3 and amines are also reported.ZusammenfassungDie Synthese der tetracyclischen Verbindung3 durch Kondensation von 1H-Benzimidazol-2-acetonitril (1) mit Cyclopentanon-2-carbonsäureester (2) in Gegenwart von Ammonacetat wird beschrieben. Die Methylierung von3 mit Trimethylphosphat liefert das N-Methylderivat4. Die Sauerstoffunktion in3 kann durch Chlor, Azid und Aminogruppen ersetzt werden.

Benzimidazole condensed ring systems, VI: Organic azides in heterocyclic synthesis, X: Synthesis of some substituted pyrimido[1,6-a]-benzimidazoles as potential antimicrobial agents

SummaryThe syntheses of 3-chloro derivatives of 2-alkyl-pyrimido[1,6-a]benzimidazol-1(2H)-ones2a, b as well as of 4,4-dichloro and 4,4-dibromo derivatives of 2-alkylpyrimido[1,6-a]benzimidazole-1,3(2H,4H)-diones3 a, b and4 are reported. Methods for converting some of the chloro compounds to azido (5, 6), amino (8), morpholino (9 a,10,11), piperidino (9 b), cyano (12), and methoxy (13) derivatives of the adopted tricyclic system are also described.ZusammenfassungDie Synthese von 3-Chlor-2-alkyl-pyrimido[1,6-a]benzimidazol-1(2H)-onen (2 a, b) und von 4,4-Dichlor- und 4,4-dibrom-pyrimido[1,6-a]benzimidazol-1,3(2H,4H)-dionen (3 a, b, 4) wird beschrieben. Diese Verbindungen lassen sich zu den entsprechenden Azido- (5, 6), Amino- (8), Morpholino- (9 a, 10, 11), Piperidino- (9 b), Cyano- (12) und Methoxy- (13) Derivaten umwandeln.

Reactions with pyrrolidine-2,4-diones, I. New synthesis of pyrano[2,3-c]pyrrole and pyrrolo[3,4-b]pyridine systems

The synthesis of some substituted 4-hydroxy-2,5,6,7-tetrahydro-pyrano[2,3-c]pyrrole-2,5-diones (5) and 4-hydroxy-1,2,6,7-tetrahydro-5H-pyrrolo[3,4-b]pyridine-2,5-diones (6) by reacting 1,5-diaryl-pyrrolidine-2,4-diones (1) and 1,5-diaryl-1,5-dihydro-4-amino-2H-pyrrol-2-ones (3) with bis-2,4,6-trichlorophenyl malonates (4) is described.ZusammenfassungDie Synthese einiger substituierter 4-Hydroxy-2,5,6,7-tetrahydro-pyrano[2,3-c]pyrrol-2,5-dione (5) und 4-Hydroxy-1,2,6,7-tetrahydro-5H-pyrrolo[3,4-b]pyridin-2,5-dione (6) gelingt durch Reaktion von 1,5-Diaryl-pyrrolidin-2,4-dion (1) bzw. 1,5-diaryl-1,5-dihydro-4-amino-2H-pyrrol-2-on (3) mit Malonsäure-bis-2,4,6-trichlorphenylester (4).

Oxadiazole condensed ring systems, I: Synthesis of 1,3,4-oxadiazolo[3,2-a]pyrimidin-5-ones as possible antimicrobial agents

SummarySyntheses of some substituted 7-hydroxy-5H-1,3,4-oxadiazolo[3,2-a]pyrimidin-5-ones (3) and their 7-methoxy (4), 7-chloro (5) and 7-azido (6) derivatives are described. 2-Phenyl-N,N′-bis(3-tolyl)propanediamide (8) was obtained, instead of the expected triazolopyrimidinone7 upon reacting3b withm-toluidine. Three compounds were screened forin vitro antibacterial and antifungal activities.ZusammenfassungDie Synthese einiger substituierter 7-Hydroxy-5H-1,3,4-oxadiazolo[3,2-a]-pyrimidin-5-one (3) und ihrer 7-methoxy (4), 7-chloro (5) und 7-azido (6) Derivate wird beschrieben. Anstelle des erwarteten Triazolo-pyrimidinons7 entsteht bei der Reaktion von3b mitm-Toluidin 2-Phenyl-N,N′-bis(3-tolyl)-propandiamid (8). Drei Verbindungen wurden auf antimikrobakterielle und fungizide Wirkung geprüft.

Reactions with pyrrolidine-2,4-diones, II: New approaches to the synthesis of substituted 5,6-dihydropyrrolo[3,4-d][1,2,3]triazol-4(2H,4H)ones

SummaryApproaches leading to 5,6-dihydro-5,6-diphenyl-2-substituted-pyrrolo[3,4-d][1,2,3]-triazol-4(2H,4H)-ones (10) are described. The first approach consists of cyclodehydrating 3(or 4)-hydroxyimino-1,5-diphenyl-4(or 3)-(4-substituted phenylhydrazono)pyrrolidin-2-ones (4,7) with boiling acetic anhydride. The second approach involves cyclization of 3(or 4)-acetoxyimino-1,5-diphenyl-4(or 3)-(4-substituted phenylhydrazono)pyrrolidin-2-ones (8,9) with elimination of acetic acid upon treatment with sodium hydroxide.ZusammenfassungEs werden zwei neue Wege zur Synthese von 5,6-dihydro-5,6-diphenyl-2-substituierten Pyrrolo[3,4-d][1,2,3]triazol-4(2H,4H)-onen (10) beschrieben. Der erste Weg besteht aus der Cyclodehydrierung von 3(oder 4)-Hydroxyimino-1,5-diphenyl-4(oder 3)-(4-subst.phenylhydrazono)pyrrolidin-2-onen (4,7) mit kochendem Essigsäureanhydrid. Der zweite Weg benutzt eine Cyclisierung von 3(oder 4)-Acetoxyimino-1,5-diphenyl-4(oder 3)-(4-subst.phenylhydrazono)-pyrrolidin-2-onen (8,9) unter Eliminierung von Essigsäure nach Behandlung mit Natriumhydroxyd.

A New Route to 1H-Pyrido[l,2-a]quinazolines

The synthesis of 2,5-disubstituted 5,6-dihydro-1 H-pyrido[1,2-a]quinazoline-1,6-diones (3) by reacting monosubstituted bis 2,4,6-trichlorophenyl malonates (1) with 3-aryl-3,4- dihydro-2-methyl-4-quinazolinones (2) is described. Allylation of the pyridoquinazoline 3c with allylbromide afforded the corresponding 3-allyloxy derivative 4. Certain generalizations of the cleavage processes of this series in the MS are reported.

Syntheses of Heterocycles, 191 Reactions of β-Aminocrotononitrile with Heterocyclic Phenolic Compounds

Condensation of β-aminocrotononitrile (2 a) with 4-hydroxycoumarin (1 a, X = O, R = R2 = H, R1 = OH) afforded the tricyclic compound 7 and the bicyclic compound 11a from 4-hydroxy-6-methyl-2-pyrone (4). Analogous compounds could not be obtained from 4-hydroxy-6-methyl-2-pyridone (5) or 4-hydroxycarbostyril (6) due to the failure of the resulting condensation products 12a and 13, respectively to undergo intramolecular cyclization. The structures assigned to 7, 11a, 12a, 18, as well as to 5-cyano-4,6-dimethyl-2-pyridone (14), obtained by self-condensation of β-aminocrotononitrile, were substantiated by spectroscopic studies.