6-methyl-2-thiouracil

These conclusions were ratified in a second paper134 which includes also 2,4-dithiouracil. The appearance of the N1H and/or N3H stretches and the absence of the SH and OH stretches in the spectrum of 2- and 4-thiouracil confirmed that these molecules exist only in the oxo-thione form. Similar findings for 2,4-dithiouracil showed that this molecule exists only as a dithione tautomeric form in an inert matrix. The spectra of S-methylated thiouracils are substantially different they present an absorption in the typical NH stretching range and another one near 3570 cm-1, which is the region characteristic for the OH stretching modes. 

Several uracil derivatives have been developed as drugs. Thus, methyl-thiouracil and propylthiouracil are thyroid inhibitors Bucolome is an antiinflammatory and Uramustine (Uracil Mustard), Fluorouracil, and its masked compounds are anticancer agents. Aminometradine and Amiso-metradine are used clinically as diuretics, and Urapidil and Ketanserin are used as antihypertensives (Scheme 5). 

Fig. 18. The bond distances (A) and bond angles (degrees) in 2-thiouracil, 4-thiouraoil, and 2,4-dithiouracil, obtained by averaging of results from crystal structure containing the bases 2-thiouracil (cf. ref. 492), 4-thiouracil (1-methyl-thiouracil 9-methyl-adenine, 4-thiouridine hydrate, 1,- )3-Z)-arab-inofuranosyl-4-thiouracil, 3 -0-acetyl-4-thiothymidine 2,4-dithiouracil...

Fiq. 7. The effect on systemic plasma calcium concentration of a 1-hour iv infusion of calcium gluconate, before and after thyroidectomy, in normal and methyl-thiouracil-treated pigs of similar age and weight. The shaded areas represent the periods of infusion (14 mg of Ca/kg of body weight/hour). [Redrawn from Duncan and Care (Dl).]... 

In a study on the effects of hormones, testosterone-treated males and estrogen-treated females had a lower incidence of amorphous pigment stones than gonadectomized animals but may have had a higher incidence of cholesterol stones the total incidence was similar (66). Progesterone, on the other hand, lowered the incidence of cholesterol stones in females. Deoxycorticosterone had no clear effect on stone formation. Desiccated thyroid lowered and methyl thiouracil raised the ratio of cholesterol/amorphous pigment stones. 

Alkylthio, arylthio, and thioxo. The thioxo group in pyrimidine-2,4-dithione can be displaced by amines, ammonia, and amine acetates, and this amination is specific for the 4-position in pyrimidines and quinazolines. 2-Substitution fails even when a 5-substituent (cf. 134) sterically prevents reaction of a secondary amine at the 4-position. Acid hydrolysis of pyrimidine-2,4-dithione is selective at the 4-position. 2-Amination of 2-thiobarbituric acid and its /S-methyl derivative has been reported. Under more basic conditions, anionization of thioxo compounds decreases the reactivity 2-thiouracil is less reactive toward hot alkali than is the iS-methyl analog. Hydrazine has been reported to replace (95°, 6 hr, 65% 3deld) the 2-thioxo group in 5-hexyl-6-methyl-2-thiouracil. Ortho and para mercapto- or thio- azines are actually in the thione form. ... 

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]. 

Among the dihydro analogues of thiouracil, 2-mercapto-6-methyl-5,6-dihydro-uracil (LXXX) retains some of the antithyroid activity exhibited by 2-thiouracils [642] (see Part 1 of this review. Volume 6). This compound can be obtained either by the condensation of thiourea with ethyl crotonate or by the hydrogenation of 2-mercapto-6-methyluracil. 

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