Synthesis of 2,3,5,6,7,8-hexahydro-3-amino-2-thioxo[1]benzothieno-[2,3-d]pyrimidin-4(1H)-one and derivatives of the new heterocyclic system 7,8,9,10-tetrahydro-3H,11H-[1]benzothieno[2',3':4,5]pyrimido[2,1-b][1,3,4]thiadiazin-11-one

Hu Y., Zheng A., Li G., Dong M., Ye F., Sun F., Liu Z., Li W.

Thieno[2,3-d]pyrimidinones were reported to act as potent anticancer agents; in this work, a series of new substituted thieno[2,3-d]pyrimidinone (6) were synthesized via the aza-Wittig reaction in satisfactory yields. The structures of these compounds were confirmed by elemental analysis, IR, 1H-NMR, and mass spectral data, and compound 6h was further analyzed by single crystal X-ray diffraction. Cytotoxic effect of all the compounds was carried out on human breast and lung cancer cell lines (MCF-7 and SPC-A-1, A459). Compound 6f exhibited the best inhibition activities against A459 with IC50 4.1 μM.

Nirogi R.V., Kambhampati R.S., Kothmirkar P., Arepalli S., Pamuleti N.R., Shinde A.K., Dubey P.K.

Several functionalized thienopyrimidines were synthesized by a facile synthetic method, which includes Gewald's reaction, and were characterized by spectral and analytical data. These functionalized thienopyrimidines were converted to various new chemical entities of biological importance, such as 2-piperazinymethyl thienopyrimidines (6, 8), 4-dimethylaminoethoxy thienopyrimidines (11), and 3-dimethylaminoethyl thienopyrimidines (12). All the compounds thus synthesized were screened for their invitro biological activities. Some of the compounds displayed promising serotonin 5-HT6 receptor antagonist activities.

Hassan A.Y.

The reaction of thiocarbohydrazide with carboxylic acids at the melting temperature allows an improved preparation of 5-substituted-4-amino-3-mercapto 1,2,4-triazoles 1 a − g . Compound 1 a reacted with 2-bromopropionic acid to give acid derivative 2 . The latter was reacted with a mixture of acetic anhydride and triethylamine to afford the mesoionic compound 3 . Heating of compound 3 in ethanol gave the ester derivative 4 , which on alkaline hydrolysis in methanol gave ketone derivative 5 . Substituted 1,2,4-triazolo [3,4-b]-6H-1,3,4-thiadiazine 6 h,i and 7 were synthesized by reaction of 1 a with acetylacetone, ethyl acetoacetate and chloroacetamide. Heterocyclic systems 8 and 9 were prepared through the reaction of 1 a with 2,3-dichloro-1,4-naphthoquinone and 2,3-dichloroquinoxaline. In addition, thenoyl isothiocyanate, thenoyl chloride, 2-thiophenecarbaldehyde, and p-chlorophenyl isocyanate reacted with compound 1 a to afford 1,2,4-triazolo[3,4-b]-1,3,4-thiadiazole ring system 10 , 11 , and urea deriv...

Prasad M.R., Raziya S., Kishore D.P.

3-Amino-2-mercapto-3,5,6,7,8,9-hexahydro-4H-cyclohepta[4,5]thieno[2,3-d]pyrimidin-4-one (4) was prepared, and from this a series of 2-(arylaminomethyl)-7,8,9,10-tetrahydro-6H,11H-cyclohepta[4,5]thieno[2,3-d][1,3,4]thiadiazolo [3,2-a]pyrimidin-11-ones (6a–d) were synthesised through the corresponding 2-chloromethyl compound (5) with aromatic amines under microwave irradiation.

Sun S., Yang X.

Litvinov V.P.

The chapter analyzes the results of studies on the synthesis, chemical transformations, and biological activities of thienopyrimidines. The known approaches to the synthesis of thienopyrimidines can be divided into two main groups: construction of the pyrimidine ring by intramolecular cyclization of thiophene derivatives and thiophene ring closure in pyrimidine derivatives. The starting thienylureas are synthesized according to known procedures based on the reactions of aminothiophenes with isocyanates, KOCN–HC1, C1SO2NCO, and some other reagents. In the synthesis of thienopyrimidines by thiophene ring, closure data are systematized according to the types of reactions giving rise to the thiophene ring. Pyrimidines starting compounds can be prepared by two methods. One of them involves substitution of the mercaptoacetic acid residue for the chlorine atom in 4-chloro-5-ethoxycarbonylpyrimidines. Another procedure for the synthesis of pyrimidines involves alkylation of 5-ethoxycarbonylpyrimidine-4(3H)-thiones with chloroacetic acid derivatives. The chemical properties of thienopyrimidines are also discussed in the chapter, where nucleophilic substitution and electrophilic substitution are described. The chapter then turns to the discussion of biological activity and some aspects of the practical use of thienopyrimidines. Certain thienopyrimidine derivatives exhibit antiallergic, antiatherosclerotic, antibacterial, anticancer, antiviral, antihypertensive, antidepressant, antihistaminic, antimicrobial, spasmolytic, analgetic, antiinflammatory, neurotropic activities, and many more. Finally, the chapter concludes by stating the analysis of the data on the chemistry of isomeric thienopyrimidines that shows that this attracts increasing interest of the chemists and biochemists.

Granata G., Barbagallo S., Perdicaro A., Marrazzo A., Santagati A., Lombardo L., Cardile V.

Methane sulfonamide derivatives of 3-amino-2-thioxo-2,3-dihydrothieno[2,3-d]pyimidin-4(1H)-one, potential selective COX-2 inhibitors, were synthesized and their structural elucidation is here reported. Some derivatives, at 10 μM concentration, showed a significant percentage of inhibition in some in vitro experiments.

Abdelhamid A.O., Elghandour A.H., Ahmed S.A., Zaki Y.H.

Pyrimido[1,2-b][1,2,4,5]tetrazin-6-one, tetrazino[3,2-b]quinazolin-5-one, pyrimidino[1,2-b]1,2,4,5-tetrazin-5-one and triazolo[4,3-a]pyrimidine derivatives were synthesized from C-(4-methyl-2-phenyl)thiazol-5-oyl-N-phenyl-hydrazonoyl bromide and different pyrimidine-2-thiones. New compounds had their structures confirmed by elemental and spectral analysis and were screened antimicrobial activity.

Ding M., Yang S., Zhu J.

The carbodiimides 4, obtained from aza-Wittig reactions of iminophosphorane 3 with aromatic isocyanates, reacted with secondary amines to give 2-dialkylamino-5,6,7,8-tetrahydro-benzothieno[2,3-d]pyrimidin-4(3H)-ones 6 in presence of catalytic EtO - Na + . Reactions of 4 with phenols or ROH in presence of catalytic K 2 CO 3 or RO - Na + gave 2-aryl(alkyl)oxy-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-ones 6 in satisfactory yields. The effects of the nucleophiles on cyclization have been investigated.

Erian A., Sherif S., Gaber H.

Santagati A., Granata G., Santagati M.

A synthetic route to the title heterocyclic system through 1,3-dipolar cycloaddition of the mesoionic compound 9 with DMAD is described. The structure elucidation of the above system is also reported.

Chowdhury A.Z., Shibata Y.

A variety of tri- and tetracyclic hetero systems were obtained by reaction of heteroaromatic ortho-aminoesters or ortho-aminonitriles with iminothioether, yielding double-annelation of a thiazolo[3,2-a]-pyrimidine, pyrimido[2,l-b]thiazine, imidazo[1,2-a]pyrimidine, and pyrimido[1,2-a]pyrimidine moieties in a one-pot process.

Santagati A., Modica M., Santagati M.

Bridgehead nitrogen heterocycles 3a, b and 6a, b containing the thieno-pyrimidine system have been prepared from the versatile intermediates 3-amino-2,3-dihydro-5,6-dimethyl-2-thioxo-thieno[2,3-d]pyrimidin-4-(1H)-one 1 and its hydrazinium or potassium salts 4; their structural elucidation is also reported.

Palkó M., Fülöp F., Evanics F., Bernáth G.

Ethyl vis- and trans-2-isothiocyanato-1-cyclopentanecarboxylates 2 and 7 were prepared by the reaction of the corresponding alicyclic ethyl 2-amino-1-carboxylates and thiophosgene. The cis-isothiocyanato compound 2 underwent ring closure with amines in one or two steps, resulting in 3-substituted-cis-2-thioxocyclopenta[d]pyrimidin-4-ones 3a-g. The trans isomer 7 failed to cyclize, but gave carboxamide 8a,b or thiourea ester derivatives 9a,b.

Santagati A., Modica M., Scolaro L.M., Santagati M.

Fused heterocyclo-quinazolines have been prepared from the versatile and easily obtained intermediate 3-amino-2,3-dihydro-2-thioxo-4(1 H)-quinazolinone 2; their structural elucidation is also reported.