The crystal and molecular structures of the following compounds showing histamine H-2-antagonist activity have been determined: (1) N-Cyano-N'-methyl-N''-{2-[(2-pyridyl)methylthio]ethyl}guanidine, C11H15N5S, M(r) = 249.33, triclinic, P1BAR, a = 7.482(2), b = 9.775(2), c = 10.019(1) angstrom, alpha = 116.00(1), beta = 102.00(2), gamma = 96.78(2)-degrees, V = 625.7 angstrom3, Z = 2, D(x) = 1.32 g cm-3, lambda(Cu Kalpha) = 1.5418 angstrom, mu = 21.21 cm-1, F(000) = 264, R = 4.98% for 2490 observed reflexions. (2) N-Cyano-N'-methyl-N''-{2-[(3-methoxy-2-pyridyl)methylthio]ethyl}guanidine, C12H17N5OS, M(r) = 279.36, monoclinic, P2(1)/a, a = 8.670(4), b = 14.095(4), c = 11.682(2) angstrom, beta = 99.32(7)-degrees, V = 1408.7 angstrom3, Z = 4, D(x) = 1.32 g cm-3, lambda(Mo Kalpha) = 0.71069 angstrom, mu = 2.3 cm-1, F(000) = 592, R = 3.72% for 1880 observed reflexions. (3) N-Cyano-N'-methyl-N''-{2-[(3-bromo-2-pyridyl)methylthio]ethyl}guanidine, C11H14-BrN5S, M(r) = 328.23, monoclinic, P2(1)/c, a = 10.928(4), b = 9.183(2), c = 14.229(8) angstrom, beta = 100.4(8)-degrees, V = 1404.42 angstrom3, Z = 4, D(x) = 1.55 g cm-3, lambda(Mo Kalpha) = 0.71069 angstrom, mu = 32.3 cm-1, F(000) = 664, R = 4.43% for 1952 observed reflexions. (4) N-Cyano-N'-methyl-N''-[4-(2-pyridyl)butyl]guanidine monohydrate, C12H17N5.H2O, M(r) = 249.31, monoclinic, I2/c, a = 15.570(8), b = 10.390(3), c = 17.383(4) angstrom, beta = 99.38(2)-degrees, V = 2774.3 angstrom3, Z = 8, D(x) = 1.19 g cm-3, lambdaA(Cu Kalpha) = 1.5418 angstrom, mu = 6.62 cm-1, F(000) = 1072, R = 4.00% for 2116 observed reflexions. (5) N-Cyano-N'-methyl-N''-[4-(3-methyl-2-pyridyl)butyl]guanidine monohydrate, C13H19N5.H2O, M(r) = 263.34, triclinic, P1BAR, a = 7.860(2), b = 9.388(1), c = 9.706(1) angstrom, alpha = 92.96(1), beta = 95.89(1), gamma = 91.49(1)-degrees, V = 708.45 angstrom3, Z = 2, D(x) = 1.23 g cm-3 , lambda(Cu Kalpha) = 1.5418 angstrom, mu = 6.72 cm-1, F(000) = 284, R = 5.16% for 2697 observed reflections. (6) N-Cyano-N'-methyl-N''-[4-(3-methoxy-2-pyridyl)butyl]guanidine, C13H19N5O, M(r) = 261.33, monoclinic, I2/c, a = 23.780(4), b = 9.162(2), c = 28.144(5) angstrom, beta = 111.47(1)-degrees, V = 5706.8 angstrom3, Z = 16, D(x) = 1.22 g cm-3, lambda(Mo Kalpha) = 0.71069 angstrom, mu = 0.88 cm-1, F(000) = 2240, R = 3.75% for 3554 observed reflexions. (7) N-Cyano-N'-methyl-N''-[4-(3-fluoro-2-pyridyl)butyl]guanidine, C12H16FN5, M(r) = 249.29, monoclinic, P2(1)/n, a = 4.6267(3), b = 13.846(1), c = 19.828(2) angstrom, beta = 93.14(1)-degrees, V = 1268.95 angstrom3, Z = 4, D(x) = 1.31 g cm-3, lambda(Cu Kalpha) = 1.5418 angstrom, mu = 7.89 cm-1, F(000) = 528, R = 6.19% for 2303 observed reflexions. (8) N-Cyano-N'-methyl-N''-[4-(3-bromo-2-pyridyl)butyl]guanidine, C12Hl6BrN5, M(r) = 310.2, monoclinic, P2(1)/c, a = 14.104(8), b = 12.678(4), c = 7.812(3) angstrom, beta = 101.92(4)-degrees, V = 1366.7 angstrom3, Z = 4, D(x) = 1.51 g cm-3, lambda(Mo Kalpha) = 0.71069 angstrom, mu = 31.77 cm-1, F(000) = 632, R = 3.7% for 1463 observed reflexions. (9) N-Cyano-N'-methyl-N''-[4-(5-methoxy-2-pyridyl)butyl]guanidine monohydrate, C13H19N50.H2O, M(r) = 279.34, triclinic, P1BAR, a = 7.700(1), b = 9.331(1), c = 10.767(1) angstrom, alpha = 78.52(1), beta = 85.56(1), gamma = 76.46(1)-degrees, V = 736.56 angstrom3, Z = 2, D(x) = 1.26 g cm-3, lambda(Mo Kalpha) = 0.71069 angstrom, mu = 0.95 cm-1, F(000) = 300, R = 4.19% for 3687 observed reflexions. The molecular dimensions and environments in the crystal are reported, together with the molecular conformations from the structure analyses and modelling studies. It is concluded that biological activity is maximized for molecules in which there is a prevalence of low-energy molecular conformations with the aromatic N-atom to N''-atom distance between 3 and 5 angstrom.
