STRUCTURES OF 9 HISTAMINE-H-2 ANTAGONISTS RELATED TO -CYANO-N'-METHYL-N''-[4-(2-PYRIDYL)BUTYL]GUANIDINE

The crystal and molecular structures of the following compounds showin g histamine H-2-antagonist activity have been determined: (1) hyl-N''- {2-[(2-pyridyl)methylthio]ethyl}guanidine, C11H15N5S, M(r) = 249.33, t riclinic, P1BAR, a = 7.482(2), b = 9.775(2), c = 10.019(1) angstrom, a lpha = 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 ang strom, mu = 21.21 cm-1, F(000) = 264, R = 4.98% for 2490 observed refl exions. (2) -[(3-methoxy-2-pyridyl)methylthio]ethyl}guanidine, C12H17N 5OS, 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) { 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) -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 = 17.38 3(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) -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)-degr ees, V = 708.45 angstrom3, Z = 2, D(x) = 1.23 g cm-3 , lambda(Cu Kalph a) = 1.5418 angstrom, mu = 6.72 cm-1, F(000) = 284, R = 5.16% for 2697 observed reflections. (6) ethyl-N''-[4-(3-methoxy-2-pyridyl)butyl]gua nidine, 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 a ngstrom, mu = 0.88 cm-1, F(000) = 2240, R = 3.75% for 3554 observed re flexions. (7) methyl-N''-[4-(3-fluoro-2-pyridyl)butyl]guanidine, C12H1 6FN5, 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 angstro m3, 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 ) -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) 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)-degr ees, 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 bio logical activity is maximized for molecules in which there is a preval ence of low-energy molecular conformations with the aromatic N-atom to N''-atom distance between 3 and 5 angstrom.