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Prizidilol, a compound combining vasodilator and beta-blocker functionalities in the same molecule, has been synthesized and characterized by Smith Kline and French Research Ltd. Crystal data: C17H25N5O2 x 1/2H2SO4 x H2O, M(r) = 398.47, orthorhombic, a = 10.722 (2), b = 11.635 (6), c = 34.105 (3) A, V = 4254.61 A3, Pbnm (non-standard form of Pnma) (D16(2h), No. 62), Z = 8, F(000) = 1704, Dx = 1.244 Mg m-3, mu(Cu K alpha) = 11.673 cm-1, R = 0.064 for 2432 independent reflections with I > 3 sigma(I). Prizidilol shows strong conformational similarities to propranolol and is protonated at the secondary amine. The 6-phenyl-3-hydrazinopyridazine residue is not planar. The hydroxy group at the asymmetric carbon is disordered so that both enantiomers are found at each molecular site. The sulfate ions and disordered water molecules lie in the crystallographic mirror plane.

The crystal and molecular structures of the following compounds showing histamine H2-antagonist activity have been determined: (1) N-Cyano-N'-methyl-N"-12[(2-pyridyl)methylthi_'o]ethyl } guanidine, C 11H 15 N5 S, Mr = 249.33, triclinic, P1, a = 7.482(2), b -- 9.775(2), c = 10.019(1) A, a -- 116.00(1),/3 = 102.00(2), "7 = 96.78(2) °, V = 625.7A 3, Z = 2, Dx = 1.32gcm -3, A(CuKa) 1.5418 A, # = 21.21 cm -~, F(000) = 264, R = 4.98% for 2490 observed reflexions. (2) N-Cyano-N'-methyl-N"- 12[(3-methoxy-2-pyridyl)methylthio]ethyl }guanidine, C12HITNsOS, Mr = 279.36, monoclinic, P21/a, a = 8.670(4), b = 14.095(4), c = 11.682(2)A, /3 = 99.32(7) ° , V = 1408.7A 3, Z = 4, Dx = 1.32gcm -3, A(MoKa) = 0.71069 A, # -- 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

The copper(II) ion is in an elogated tetragonally distorted octahedral environment in all four compounds. The ethoxyacetate ligand is unidentate in the tetraammine compound, but the hydroxy- and alkoxycarboxylate ligands from trans-planar five-membered chelate rings in the other three compounds. Cooperative variations in the dimensions of the copper(II) coordination sphere may be ascribed to the different σ donors powers of the ligand

Treatment of 3-aroyloxy- and 2-(aroyloxymethyl)tetrahydrofurans with TiCl4 results in cleavage of the heterocyclic ring with intervention by the appropriately situated ester group to form intermediates which, on work-up and hydrolysis, furnish 1,4-diols.

5-(1,3-Benzodioxol-5-ylmethyl)-2-[2-(5-methyl-1H-imidazol-4-ylmethylthio)ethylamino]-4(1H)-pyrimidone dihydrochloride C 19 H 23 N 5 O 3 S 2+ .2Cl - , M r =472.4, triclinic, P1l, a=8.291 (2), b=10.759 (3), c=13.169 (3) A, α=108.42 (2), β=93.28 (2), γ=100.3 (3) o , V=1088.6 A 3 , Z=2, D x =1.44 Mg m -3 , λ(Mo Kα)=0.7107 A, μ=0.42 mm -1 , F(000)=492, T=294 K, final R=0.038 for 3184 unique observed reflexions. All bonded distances and interbond angles lie within the range of values for compounds of a similar nature

5-(1,3-Benzodioxol-5-ylmethyl)-2-[2-(5-methyl-1H-imidazol-4-ylmethylthio)ethylamino]-4(1H)-pyrimidone dihydrochloride C 19 H 23 N 5 O 3 S 2+ .2Cl - , M r =472.4, triclinic, P1l, a=8.291 (2), b=10.759 (3), c=13.169 (3) A, α=108.42 (2), β=93.28 (2), γ=100.3 (3) o , V=1088.6 A 3 , Z=2, D x =1.44 Mg m -3 , λ(Mo Kα)=0.7107 A, μ=0.42 mm -1 , F(000)=492, T=294 K, final R=0.038 for 3184 unique observed reflexions. All bonded distances and interbond angles lie within the range of values for compounds of a similar nature

Kara, Hülya (Balikesir Author), The title compound, μ-[1,3-bis(5-chloro-2- oxidobenzylideneamino)propan-2-olato(3-)]-O,N,O′:O′, N′,O″-μ-(3,5-dimethyl-pyrazolato)-N:N′-dinickel(II), [Ni2(C17H13Cl2N2O3) (C5H7-N2)], has crystallographic mirror symmetry. The Ni atoms in the dinuclear structure are linked symmetrically by the N atoms of the 3,5-dimethylpyrazole group and by the alkoxo O atom. Each NiII ion is coordinated by two N atoms and two O atoms, forming a square plane with trans-N2O2 geometry.

The crystal and molecular structures of ten compounds with strong structural resemblances to the cimetidine group of histamine H2-receptor antagonists, but exhibiting selective H1-receptor antagonist activity, (1)-(7), or H1 and H2 activity (8)-(10), have been determined: (1) 2-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-5- (6-methyl-3-pyridylmethyl)-4-pyrimidone trihydrobromide (temalastine), C21H27BrN5O3+.3Br-, M(r) = 685.09, triclinic, P1, a = 6.314 (2), b = 11.192 (2), c = 19.441 (5) A, alpha = 102.47 (2), beta = 92.77 (2), gamma = 103.28 (2) degrees, V = 1298.51 A3, Z = 2, Dx = 1.75 g cm-3, mu = 61.6 cm-1, F(000) = 672, R = 2.93% for 3208 independent reflexions. (2) 2-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-4-pyrimidone, C14H19BrN4O2, M(r) = 355.23, monoclinic, I2/a, a = 16.359 (3), b = 10.469 (6), c = 18.339 (4) A, beta = 90.90 (2) degrees, V = 3140.49 A3, Z = 8, Dx = 1.503 g cm-3, mu = 26.0 cm-1, F(000) = 1176, R = 4.2% for 1872 independent reflexions. (3) 3-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-4- amino-1,2,5-thiadiazole-1-oxide, C12H16BrN5OS, M(r) = 358.26, triclinic, P1, a = 14.295 (2), b = 12.447 (2), c = 9.917 (2) A, alpha = 95.77 (2), beta = 113.86 (2), gamma = 106.91 (1) degrees, V = 1495.18 A3, Z = 4, Dx = 1.59 g cm-3, mu = 50.96 cm-1, F(000) = 728, R = 5.98% for 5674 independent reflexions. (4) 3-[4-(5-Bromo-3-methyl-2-pyridyl)butylamino]-4- benzylamino-1,2,5-thiadiazole-1-oxide, C19H22BrN5OS, M(r) = 448.38, monoclinic, P2(1)/c, a = 36.293 (7), b = 4.826 (2), c = 11.528 (3) A, beta = 96.91 (2) degrees, V = 2004.27 A3, Z = 4, Dx = 1.49 g cm-3, mu = 39.2 cm-1, F(000) = 920, R = 12.1% for 1945 independent reflexions. (5) 2-[3-(N-Benzyl-N-2- pyridylamino)propylamino]-4-pyrimidone, C19H21N5O, M(r) = 335.4, orthorhombic, Pbna, a = 7.082 (1), b = 19.889 (3), c = 24.899 (3) A, V = 3507.16 A3, Z = 8, Dx = 1.27 g cm-3, mu = 6.24 cm-1, F(000) = 1424, R = 4.05% from 2470 independent reflexions. (6) 3-[3-(N-4-Fluorobenzyl-N-2- pyridylamino)propylamino]-4-ethylamino-1,2,5-thiadiazole-1-oxide, C19H23FN6OS, M(r) = 402.5, monoclinic, P2(1)/n, a = 6.686 (2), b = 14.717 (3), c = 20.850 (5) A, beta = 97.83 (2) degrees, V = 2032.47 A3, Z = 4, Dx = 1.32 g cm-3, mu = 16.41 cm-1, F(000) = 848, R = 8.5% from 2484 independent reflexions. (7) 5-(6-Methyl-3-pyridylmethyl)-2-[3-(5,6,7,8-tetrahydro-8- quinolyl)propylamino]-4-pyrimidone, C23H29N5O2, M(r) = 407.5, monoclinic, P2(1)/c, a = 14.966 (2), b = 16.075 (2), c = 9.1608 (9) A, beta = 99.158 (8) degrees, V = 2175.83 A3, Z = 4, Dx = 1.24 g cm-3, mu = 6.19 cm-1; F(000) = 872, R = 5.3% from 2784 independent reflexions. (8) 2-(4-Phenylbutylamino)-5-(3-pyridyl-methyl)-4-pyrimidone, C20H26N4O3, M(r) = 370.5, monoclinic, P2(1)/c, a = 8.040 (4), b = 21.279 (4), c = 11.404 (2) A, beta = 92.08 (5) degrees, V = 1949.68 A3, Z = 4, Dx = 1.26 g cm-3, mu = 0.93 cm-1, F(000) = 792, R = 4.05% from 3816 independent reflexions.(ABSTRACT TRUNCATED AT 400 WORDS)

The crystal and molecular structures of 11 6-substituted pyridazinone derivatives: 6-phenyl-3(2H)-pyridazinone-acetic acid (1/1) (1), 6-(4-aminophenyl)- 3(2H)-pyridazinone (2), 6-(4-aminophenyl)- 5-methyl-3(2H)-pyridazinone (3), 6-(4-acetamidophenyl)- 3(2H)-pyridazinone (4), 6-(4-acetamido-2- methoxyphenyl)-3(2H)-pyridazinone (5), 6-(2-aminophenyl)-3(2H)- pyridazinone (6), 6-phenyl-3(2H)- pyrazinone (7), 6-(4-aminophenyl)-4,5-dihydro- 3(2H)-pyridazinone (8), (R)-(-)-6[4-(3-bromopropionamido)phenyl]- 4,5-dihydro-5-methyl-3(2H)-pyridazinone (9), (R)-(-)-6-(4-ammoniophenyl)-4,5- dihydro-5-methyl-3(2H)-pyridazinone (-)-tartrate-dichloromethane-methanol (1/1/1) (10), 4,5-dihydro-6-methyl-3(2H)-pyridazinone (11) have been determined as part of a study to determine the relationship between their cardiovascular properties and molecular structure and dimensions. For the two optically resolved chiral derivatives (9) and (10) the absolute configuration has been determined.

Substitution of a methyl group in the 11-position of benzo[a]pyrene (B[a]P) enhances its carcinogenicity. An X-ray crystallographic determination of the three-dimensional structure of 11-methylbenzo[a]pyrene (11-MeB[a]P) shows that steric overcrowding in the bay region is relieved somewhat by distortions of the bay-region bond angles in the plane of the ring system. A comparison with the structure of 7,12-dimethylbenz[a]anthracene (DMBA), which shows out-of-plane distortions to relieve such strain, shows that, in general, H...H intramolecular interactions between neighboring rings in a polycyclic aromatic hydrocarbon are the primary determinants of the nature of the molecular distortions as a result of steric overcrowding (mainly in-plane for 11-MeB[a]P and mainly out-of-plane for DMBA). The 11-MeB[a]P molecule exhibits considerable flexibility as evidenced by slightly different conformations in the two molecules found in the asymmetric unit of the crystal. One molecule is fairly flat with bond angle distortions in the bay region, while the other is slightly buckled as a result of some twist (15 degrees) in the bay region. Computer modeling indicates that steric overcrowding as a result of the bay-region 11-methyl group may affect the conformation of the ring that bears the diol and epoxide groups in the anti-diolepoxide. The nature of this distortion may, in turn, provide a clue to the reason for the greater carcinogenicity of B[a]P when methylated at the 11-position in the non-benzo bay region site. In addition, the 11-methyl group, because of its bulk, may affect the orientation of the polycyclic hydrocarbon as it lies between the nucleic-acid bases when covalently bound to DNA.

A carbotricycle (13) having the same relative stereochemistry as the phorbols at 6 centres has been constructed via stereoselective Intramolecular Diels–Alder reaction of furans (IMDAF) of a precursor (7) possessing a Z-vinylogous ketoester followed by selective epimerisation at C-10 of the initial cycloadduct (11); whereas the corresponding E-isomer (8) or alkyne (3) show no stereoselection in the IMDAF.

The crystal and molecular structure of the title compound has been determined by Patterson heavyatom methods and refined to R = 0.066 {triclinic, a = 11.708 (5), b = 11.596 (5), c = 7.750 (3) A, a = 86.33 (2), fl = 82.92 (2), y = 73.26 (3) °, space group Pi, Mo Ka radiation, 1334 reflections [1 > 3a(I)l}. The bis(r/-cyclopentadienyl)molybdenum moiety has the eclipsed configuration and the Mo-Mg bond length is 2.732 A. The presence of the hydrido ligand is inferred from the molecular geometry. The Mg atom has a distorted tetrahedral configuration.

The compounds [TiCl3(dmpe)R](R = Me, CH2D, or Et; dmpe = Me2PCH2CH2PMe2) have been prepared. An X-ray crystal structure determination of [TiCl3(dmpe)Et] shows that the Ti–C–C angle of the Ti–Et moiety is 86.3(6)°. Variable-temperature n.m.r. studies show the molecule to be fluxional at room temperature. At –90 °C the n.m.r. spectra correspond to the structure found in the crystal and J(C–H) for the ethyl CH2 hydrogens is 150.2 Hz. It is concluded that the ethyl group is bonded by a [graphic omitted] system. The crystal structure of [TiCl3(dmpe)Me] has been determined from X-ray and neutron diffraction data. The data show the methyl group to be distorted such that it is tilted with respect to the Ti–C vector and one hydrogen atom closely approaches the Ti centre giving an angle for Ti–C–H of 93.5(2)°(neutron data). Variabletemperature n.m.r. studies show that [TiCl3(dmpe)R](R = CH3 or CH2D) are fluxional but provide no evidence for differentiation of the C–H moiety of the methyl group.

The compounds [M(η-C6H5R)(σ,η5-C5H4CR′2)](M = Mo or W, R = H, R′= Me or Ph; M = W, R = Me, R′= Me or Ph), [W(η-C6H3Me3-1,3,5)(σ,η5-C5H4CPh2)], [Ti(σ,η5-C5H4CPh2)2], and [Ti(σ,η5-C5H4CPh2)2(CO)] are described. The crystal structures of the compounds where M = Mo, R = H, R′= Me or Ph; M = W, R = Me, R′= Me or Ph; and [Ti(σ,η5-C5H4CPh2)2] have been determined and reveal that the exocyclic carbon of the fulvene ligands is strongly bent out of the plane of the C5-ring carbons and bonds directly to the metal. The metal–fulvene bonding is discussed in the light of the structures, the photoelectron spectra, and molecular orbital calculations.

Bis(η-toluene)titanium reacts with cycloheptatriene in the presence of (AlEtCl2)2, at > 60 °C to form [Ti(η-C7H7)(η-C7H9)] and at room temperature [{Ti(η-C7H7)(thf)(µ-Cl)}2](thf = tetrahydrofuran) is also formed. The crystal structure of the latter has been determined. The dimer reacts with the ligands L2= R2PCH2CH2PR2(R = Me or Ph), trans-1,2-bis(dimethylphosphino)cyclopentane, MeOCH2CH2OMe, 2PMe3 or Me2NCH2CH2NMe2, forming the compounds [Ti(η-C7H7)L2Cl]. Reaction of alkyl Grignard reagents with the appropriate chloroderivatives gives the titanium–alkyls [Ti(η-C7H7)L2R][L2= Me2PCH2CH2PMe2, R = Me or Et; L2=trans-1,2-C5H8(PMe2)2, R = Me]. The crystal structure of [Ti(η-C7H7)(Me2PCH2CH2PMe2)Et] has been determined: there is no evidence for Ti–H–C interactions between the Ti and the hydrogens of the ethyl group. The photoelectron spectra of several Ti(η-C7H7) compounds are discussed in terms of the nature of the Ti(η-C7H7) bonding. It is proposed that the chemistry of the Ti(η-C7H7) system corresponds most closely to a formal description of the η-C7H7 group as having a –3 charge rather than the more conventional description as +1. Homogeneous mixtures of [{Ti(η-C7H7)(thf)(µ-Cl)}2] and aluminium alkyls are shown to catalyse ethylene polymerisation.

Crystals of the title compound are monoclinic, a= 7·064, b= 7·668, c= 7·256 all ± 0·003 A;, γ= 88·81 ± 0·005 °, space group P21/n, Z= 2. The structure was determined from diffractometer data (555 independent reflections) by three-dimensional X-ray methods and refined by least squares to R 0·053. The crystals are formed from trans-bis(aminomethanesulphonato)copper(II) chelates at centres of symmetry, linked into, a three-dimensional array by hydrogen bonds and the long copper–sulphonate-oxygen contacts which give copper a distorted octahedral co-ordination-sphere (Cu–O 1·995 and 2·506. Cu–N 1·999 A).