الفهرس 
CHAPTER IOnly 14 pages are availabe for public view
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Abstract
The high herbicidal activities of 1,2,4-triazolo[1,5-c]pyrimidine and 2H-1,2,4-thiadiazolo[2,3-a]pyrimidine derivatives suggested the development of new fused heterocyclic compounds for application as herbicides(40). Some series of pyrimidinyl-substituted thioureas and amides were synthesized and the typical crystal structure of a 2H-1,2,4-thiadiazolo[2,3-a]pyrimidine derivative was determined by X-ray diffraction. All the compounds were tested for their herbicidal activity against selected weeds. The series of fused heterocyclic amides exhibited high herbicidal activities both against monocotyledonous weeds in pre-emergence treatments. Different substituents at the meta positions of the pyrimidine ring were found to affect the herbicidal activity(40).
2,4-Diamino-7H-pyrrolo[2, 3-d]pyrimidines with a phenyl or benzyl group at the 5-position were synthesized(41) as inhibitors of dihydrofolate reductase (DHFR) from Pneumocystis carinii and Toxoplasma gondii which were the two potentially life-threatening opportunistic pathogens related with AIDS and other disorders of the immune system.
Aldol condensation of paraformaldehyde with substituted benzaldehyde or with phenylacetaldehyde gave α-hydroxyketones with a phenyl or benzyl group at the 4-position. Further reaction of the hydroxyketones with malononitrile afforded 2-aminofuran-3-carbonitriles which upon heating with guanidine underwent ring transformation/ring annulation to produce 2,4-diamino-7H-pyrrolo[2,3-d]pyrimidines rather than 2,4-diaminofuro[2,3-d]pyrimidines. One of the target compounds obtained in this manner, 2,4-diamino-5-(3,4,5-trimethoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidine, might be viewed as a conformationally limited analogue of trimethoprim which was an antimicrobial agent widely used in combination with a sulfa drug to treat P. carinii and T. gondii opportunistic infections in patients with AIDS(41).
Several compounds were estimated as ligands of toxoplasma gondii uracil phosphoribosyltransferase (UPRTase) by testing their ability to inhibit this enzyme in vitro(42). More effective compounds such as 2-thiopyrimidine, 1-deazauracil and 2,4-dithiouracil bounded to the enzyme much better than two known substrates for T.gondii, UPRTase, 5-fluorouracil and emimycin which have antioxoplasmal activity. In addition, several selected compounds were evaluated as substrates for T.gondii UPRTase, such as 2,4-dithiouracil. Also, a number of nucleobase analogs were evaluated as potential inhibitors of T. gondii uridine phosphorylase (Urdpase). Based on the inhibition data, a structure-activity relationship for the binding of nucleobase analogs to the enzyme was made using uracil as a reference compound. A comparison of the results from T.gondii study with those from similar studies on mammalian Urdpase and thymidine phosphorylase (dThdpase) dedected that there are both similarities and differences between the catalytic site of T.gondii Urdpase and the mammalian enzymes with respect to binding of uracil analogs. 6-Benzyl-2-thiouracil was identified as a powerful and specific inhibitor of T.gondii Urdpase, compared to mammalian Urdpase and Thdpase(42).
The antimony (III) complex with heterocyclic thioamide, 2-mercaptopyrimidine (ptmH), of formula [Sb(ptm).0.5CH3OH], has been synthesized and characterized by elemental analysis, 1H, 13C NMR and FT-IR spectroscopic techniques(43). The toxicity of the compound against tumer pleiomorphic cells which has been isolated from a leiomyosarcoma tumor in the Wistar rat was studied in vitro. The results show that the coumpound did not destroy or prevent multiplication in vitro of leiomyosarcoma cells in low doses. The influence of the compound was in the platelet
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accumlation, which correlates with the above tumor cells enhanced metastatic potential which also has been studied. The anti-metastatic ability study shows that the complex prevented cancer cell stimulated aggregation up to the value of 10% in all mM concentrations tested(43).
1.2. Structural chemistry of pyrimidine compounds:
The hydrogen bonding interaction of cytosine-modeling compound (4-aminopyrimidine) with water was investigated with the use of a combined experimental matrix-isolation FT-IR and theoretical ab initio method(44). The closed N - H---O - H---N(3) Structure containing two H-bonds was found to be significantly more stable than the singly H-bonding structures N(1)---HO-H and N-H---OH by 8.0 and 10.2 KJ/mol, respectively(44). The relative stabilities of a series of tautomers of 2-thiouracil (2-TU), 6-amino-2-thiouracil (ATU) and 6-aminouracil (6-AU) were inspected using the all-valence CNDO/2 method. For 2-ATU, the thione-enol form is the most stable.