Thiouracils structure

Thiouracils Structures, Tautomerism, Interaction with Water... 

Hyperthyroidism may be treated in several ways. One of these is interference with the synthesis of the thyroid hormones, possibly by removal of iodine. Thiourea and cyclic thioureas have this effect and of such cyclic compounds, thiouracil (1030 R = H), its 6-alkyl derivatives (1030 R = Me or Pr) and thiobarbital (1031) are effective thyroid drugs. Today only propylthiouracil (1030 R = Pr) is widely used, probably because it has fewer side effects than the others (71MI21302). The thiouracils are made by the Principal Synthesis from a /3-oxo ester (1032 R = H, Me, Pr, etc.) and thiourea (45JA2197) their fine structures are experimentally based (64AF1004). 

Progressive departure from the fundamental structure of the lead agent cimetidine led to the anti ulcer agent oxmetidine (47). The synthesis involves -methylation (CH3I) of the 2-thiouracil intermediate and is followed by an addition-elimination reaction with 2-(5-methyl-4-imidazolylmethylthio) ethylamine to give oxmetidine (47). ... 

Abstract This presentation is a brief review on the resnlts of our work on iodine interaction with thioamides, selenoamides and amides. The thioamides, benzothia-zole-2-thione (BZT) (1), 6-n-propyl-2-thiouracil (PTU) (2), 5-chloro-2-mercap-tobenzothiazole (CMBZT) (3), N-methyl-benzothiazole-2-thione (NMBZT) (4), benzimidazole-2-thione (BZIM) (5), thiazolidine-2-thione (TZD) (6), 2-mercapto-pyridine (PYSH) (7), 2-mercapto-nicotinic acid (MNA) (8), 2-mercapto-benzoic acid (MBA) (9) and 2-mercapto-pyrimidine (PMT) (10) react with producing three type of complexes of formulae [(HL)IJ(l2) (HL= thioamide and n= 0, 1), [(HL) [I3 ] and [(HL-L)]+[l3 ]. The interaction of seleno-amides, derived from, 6-n-propyl-2-thiouracil (RSelJ) (R= Me- (11), Et- (12), n-Pr- (13) and i-Pr- (14)) with I, have also been studied and produced the complexes [(RSeU)IJ of spoke structure. These complexes are stable in non-polar solvents, but they decompose in polar solvents, producing dimeric diselenide compounds or undertake deselenation. 

A structurally related 2-thio analogue, 4-amino-5-methyl-2-thiouracil (LVII) possesses growth inhibition against L. leichmannii. This inhibition could be reversed in a non-competitive manner by vitamin B12 [408]. 

Fig. 29.19 LC-APCI-MS of thiouracil. Left upper panel, structure of thiouracil lower panel, full scan spectrum of thiouracil standard (2.5 g) using a cone voltage of 35 V. Right SIM spectra, cone voltage 10 V, m/z 129, normalized to 4.00 10 . Upper panel, standard, equivalent to 0.33 g thiouracil/g thyroid centre panel, known negative thyroid lower panel, negative thyroid fortified with thiouracil at 0.20 g/g. (From Ref. 626 — Reproduced by permission of The Royal Society of Chemistry.)...

Figures 18 and 19 collect the averaged geometrical parameters for thiouracils and thiocytosine. The geometrical structures of the two isocytosine tautomers can be found in the paper by Sharma and...

The X-ray crystallographic studies show that thiouracils and 2-thiocytosine exists in the crystalline state in forms 51 and 52, respectively, and that isocytosine exists as a mixture of two amine-lactam forms, 42 and 43. Several experimental studies on these pyrimidines in solution confirm the conclusions from the crystal. However, studies on the tautomerism of the minor pyrimidine bases are few. In a number of cases the conclusions about the dominant structures are intuitive rather than proved. We present the essential experimental data on the structure of the minor pyrimidine bases. 

In the case of 4-thiouracil it is possible to compare its UV spectrum with that of l,6-dimethyl-4-methylthiouracil.516 As the spectra are different from each other, 4-thiouracil is supposed not to exist in form 58. The comparison of the UV spectrum of 4-thiouracil with those of some 5-methoxy-4-thiouracil nucleosides382 indicates that the pyrimidine residues of the latter have the same structure as that of 4-thiouracil... 

CH3), which was converted with aqueous alkali to 5 -methyl-2 -thiouri-dine.233 Similarly, 3-ethoxyacryloyl isothiocyanate (LXXI, R = H, R" = C2H5) plus LXX yielded the tribenzoate ester of LXXIII (R = H) which was converted with sodium alkoxide or ammonia to 2 -thiouridine. These D-ribo-2 -thionucleosides exhibit ultraviolet spectral properties similar to those shown by l-methyl-2-thiouracil123 and an enzymically prepared sample of 2 -thiouridine.236 Treatment of 2 -thiouridine with monochloroacetic acid afforded uridine this finding permitted assignment of the l-(/ -D-ribo-furanosyl) structure to these 2-thiouracil nucleosides.233... 

Fig. 1.4.5. The structures of isoquinoline derivatives 9 and uracil and thiouracil derivatives 10. 1.4.4...

---