Synthesis and biological activity of aminopyrrolo[3,2-d]pyrimidines

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 22, No. 2, pp. 185–191, February, 1988.     

Synthesis and antitumor activity of pyrrolo [3,2-d]pyrimidines

Translated from Khimiko-farmatsevticheskii Zhurnal, Vol. 25, No. 12, pp. 19–23, December, 1991.     

Synthesis of new [1,3,4]thiadiazolo[3,2-a]thieno[2,3-d]pyrimidinone derivatives with antiinflammatory activity

New thiadiazolothienopyrimidinones were synthesized in continuation of efforts to prepare thienopyrimidine derivatives with analgesic and antiinflammatory activities. In this study, the effect of various substituents in the thiophene ring on the pharmacological activity of the compounds was investigated.     

Synthesis, antimalarial activity, and molecular modeling of new pyrrolo[1,2-a]quinoxalines, bispyrrolo[1,2-a]quinoxalines, bispyrido[3,2-e]pyrrolo[1,2-a]pyrazines, and bispyrrolo[1,2-a]thieno[3,2-e]pyrazines

Three pyrrolo[1,2-a]quinoxalines, 15 bispyrrolo[1,2-a]quinoxalines, bispyrido[3,2-e]pyrrolo[1,2-a]pyrazines, and bispyrrolo[1,2-a]thieno[3,2-e]pyrazines were synthesized from various substituted nitroanilines or nitropyridines and tested for their in vitro activity upon the erythrocytic development of Plasmodium falciparum strains with different chloroquine-resistance status. Bispyrrolo[1,2-a]quinoxalines showed superior antimalarial activity with respect to monopyrrolo[1,2-a]quinoxalines. The best activity was observed with bispyrrolo[1,2-a]quinoxalines linked by a bis(3-aminopropyl)piperazine. Moreover, it was observed that the presence of a methoxy group on the pyrrolo[1,2-a]quinoxaline nucleus increased the pharmacological activity. Drug effects upon beta-hematin formation were assayed and showed similar or higher inhibitory activities than CQ. A possible mechanism of interaction implicating binding of pyrroloquinoxalines to beta-hematin was supported by molecular modeling.     

Synthesis of substituted pyrimidines, pyrazole[3,4-d]pyrimidines and imidazo[4,5-d]pyrimidines and evaluation of their antifungal activity

Some pyrimidines, pyrazolo[3,4-d]pyrimidines and imidazo[4,5-d]pyrimidines bearing the 5-nitro- and 5-aminothienyl-2-sulfide functionalities on the pyrimidine nucleus were synthesized and evaluated for their antifungal activity against several strains of yeasts and dermatophytes. 4-Amino-2-pyrimidinyl-5'-nitro-2'-thienylsulfide (Va) resulted active against both yeasts and dermatophytes (about 30 fold less potent than Miconazole). Compds. (II b), (V b) and (VIII b) showed only a slight activity against dermatophytes, while the other compounds were inactive.     

Synthesis and antibacterial activity of 3,4-dihyhdropyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-ones

A series of 3,4-dihydropyrido[3′,2′:4,5]thieno[3,2-d]pyrimidin-4-ones were synthesized by the reaction of ethyl 3-alkyl(aryl)carboxamidothieno[2,3-b]pyridine-2-carboxylates with aliphatic amines. The starting carboxamides were obtained via the reaction of ethyl 3-aminothieno[2,3-b]pyridine-2-carboxylate with acid chlorides. It is established that the synthesized pyridothienopyrimidinones possess antistaphylococcal activity. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 42, No. 9, pp. 37–39, September, 2008.     

Derivatives of condensed thienopyrimidines: Synthesis and anticonvulsant and tranquilizer activity of hydrochlorides of pyrano[4′,3′:4,5]thieno[3,2-e]imidazo[1,2-a]pyrimidines

New methods for the synthesis of 4-substituted 6,7-dihydro-7,7-dimethyl-5-oxo-9H-pyrano-[4′,3′: 4,5]-thieno[3,2-e]imidazo[1,2-a]pyrimidines and their hydrochlorides are developed. The anticonvulsant and tranquilizer properties of newly synthesized compounds have been studied. __________ Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 41, No. 11, pp. 22–24, November, 2007.     

4H-Pyrrolo[1,2-a]thieno[3,2-f] and 4H-pyrrolo[1,2-a]thieno-[2,3-f][1,4]diazepines: Synthesis and Pharmacological Evaluation

As an extension of a previous work, in which a number of 4H-pyrrolo-[1,2-a]thieno[2,3-f][1,4]diazepines were described, a new series of derivatives of the isomeric pyrrolo[1,2-a]thieno[3,2-f]diazepines ring system has been synthesized. The products obtained, together with those reported in the previous paper, were tested for acute toxicity and CNS activity in mice.     

Synthesis of novel thieno[2,3-d]pyrimidine, thieno[2,3-b]pyridine and thiazolo[3,2-a]thieno[2,3-d]pyrimidine derivatives and their effect on the production of mycotoxins.

The thiophene derivative 1 reacts with the active methylene reagents 2a-c to afford the thieno[2,3-d]pyrimidine derivatives 6a,b and 8, respectively. 1 reacts with phenacyl bromide 2d to afford the N-alkylation product 9 and reacts with phenacyl thiocyanate 2e to afford the N-(thiazol-2-yl) derivative 10, which was further cyclized into thiazolo[3,2-a]thieno[2,3-d]pyrimidine derivative 12. Compound 1 reacts also with the cinnamonitriles 3a,b to afford the thieno[2,3-b]pyridines 15a,b, respectively. 1 undergoes either acetylation or hydrolysis to afford the thieno[2,3-b]pyridine derivative 19 and the thiophene derivative 22, respectively. Some of the new compounds show inhibitory effect to the production of mycotoxins and to fungal growth.     

Synthesis and antimicrobial study of novel 1-aryl-2-oxo-indano[3,2-d]pyrido/pyrimido[1,2-b]pyrimidines

A series of 2-(arylidene)-indan-1, 3-diones 1 were prepared by Knoevenagel reaction between indane-1,3-dione and the appropriate araldehydes. The alpha,beta-enones 1 have been used as a component of Michael addition with equimolar amounts of 2-aminopyridine/2-aminopyrimidine to give novel heterocyclic systems 4 and 5, respectively. They are reported here for the first time. The structures of the newly synthesized compounds were confirmed by IR, (1)H-NMR, (13)C-NMR, and elemental analysis. All compounds were screened for their antibacterial and antifungal activities. Some of them showed promising activities.     

Synthesis and pharmacological evaluation of newer thiazolo [3,2-a] pyrimidines for anti-inflammatory and antinociceptive activity

A new series of thiazolo [3,2-a] pyrimidine derivatives was designed and synthesized using 4-fluoroaniline and ethylacetoacetate as starting material. Anti-inflammatory activity was assessed by the rat paw edema method and antinociceptive activity was evaluated by thermal stimulus technique. The compounds 5-(4-chlorophenyl)-2-(4-fluorobenzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid (4-fluorophenyl)amide (3l) and 2-(4-chlorobenzylidene)-5-(4-fluorophenyl)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid (4-fluorophenyl)amide (3q) were found to possess significant anti-inflammatory and antinociceptive activities. These compounds also showed lower ulcerogenic activity and higher ALD₅₀ values. Compounds with an aryl ring substituted with a smaller electron withdrawing group at the fourth position displayed better activity than the other derivatives.