Structure of 5-chloro-2-(3-[(diethylamino)methyl]-5-methyl-4H-1,2,4- triazol-4-yl)benzophenone (I) and of its methylamino analogue (II).

(I) C21H23C1N4O, Mr = 382.9, monoclinic, C2/c, a = 8.914 (4), b = 15.553 (4), c = 28.808 (7) A, beta = 92.88 (3) degrees, V = 3988.9 A3, Z = 8, Dx = 1.275 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 2.03 cm-1, F(000) = 1616, T = 294 K, R = 0.0547 for 795 observed reflections. (II) C18H17C1N4O, Mr = 340.8, triclinic, P1-, a = 7.381 (6), b = 8.345 (3), c = 14.955 (4) A, alpha = 89.72 (2), beta = 78.89 (4), gamma = 68.97 (4) degrees, V = 841.6 A3, Z = 2, Dx = 1.345 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 2.32 cm-1, F(000) = 356, T = 293 K, R = 0.0412 for 2447 observed reflections. Both benzophenones can be formally derived from the triazolobenzodiazepine alprazolam by splitting of the C = N double bond of the seven-membered heterocyclic ring. In (I) the N(5)...C(6) distance is 4.94 (1) A and the seven-atom chain bears little resemblance to its seven-membered ring precursor. In (II), however, the corresponding N...C distance is only 3.494 (3) A and the seven-atom chain is more nearly ring shaped. Corresponding bond lengths and angles in the two structures are generally similar and agree well with accepted values.

Structure of 9-chloro-7-(2-chlorophenyl)-3,5-dihydro-[1,2,4] triazino[4,3-a][1,4]benzodiazepin-2(1H)-one.

C17H12Cl2N4O, Mr = 359.2, triclinic, P1-, a = 8.777 (8), b = 12.715 (4), c = 14.883 (4) A, alpha = 95.69 (2), beta = 83.62 (3), gamma = 93.46 (3) degrees, V = 1640.5 A3, Z = 4, Dx = 1.454 g cm-3, lambda(Mo K alpha) = 0.71069 A, mu = 3.99 cm-1, F(000) = 736, T = 293 K, R = 0.039 for 2783 observed reflections. The seven-membered heterocyclic ring has a cycloheptatriene-like boat conformation with bow and stern angles 60.5 (8) and 33.8 (8) degrees, and 59.8 (8) and 35.9 (8) degrees, respectively, in the two independent molecules. The triazino ring is near planar in both molecules. The angles between the 7-phenyl ring and the fused benzo moiety are 88.9 (8) and 82.0 (8) degrees. Corresponding bond lengths and angles in the two molecules are generally similar and agree well with accepted values.

5-Methyl-2'-deoxy-4'-thio-alpha-uridine (R)-S-oxide.

The pyrimidine ring of the title compound, C(10)H(14)N(2)O(5)S, is planar to within 0.024 (1) A and makes an angle of 75.46 (10) degrees with the mean plane of the thiosugar ring. In terms of standard nucleoside nomenclature, this ring has the C3'-endo conformation. The O5'-C5'-C4'-C3' torsion angle is 166.5 (3) degrees and the glycosidic torsion angle S4'-C1'-N1-C2 is -52.1 (2) degrees (syn).

Some 6-aza-5-substituted-2'-deoxyuridines show potent and selective inhibition of herpes simplex virus type 1 thymidine kinase.

The synthesis and X-ray crystal structures of a series of 5-substituted-6-aza-2'-deoxyuridines is reported. These nucleoside analogues inhibit the phosphorylation of thymidine by HSV-1 TK but have no effect on the corresponding human enzyme. Detailed examination of one analogue proves it to be a competitive inhibitor of thymidine with a Ki of 0.34 microM and is a very poor substrate. The analogues are not substrates for the enzyme and also do not inhibit the degradation of thymidine by thymidine phosphorylase. Molecular modelling showed that the inhibitors fit well in the active site of HSV-1 TK, provided the conformation of the sugar moiety is the same for thymidine in the complex.