Phenazine–naphthalene-1,5-diamine–water (1/1/2)

The asymmetric unit of the title compound, C12H8N2·C10H10N2·2H2O, contains one half-mol­ecule of phenazine, one half-mol­ecule of naphthalene-1,5-diamine and one water mol­ecule. The phenazine and naphthalene-1,5-diamine mol­ecules are located on inversion centers. The water mol­ecules serve as bridges between the naphthalene-1,5-diamine mol­ecules and also between the naphthalene-1,5-diamine and phenazine mol­ecules. The naphthalene-1,5-diamine and water mol­ecules are connected via N—H⋯O and O—H⋯N hydrogen bonds, forming a T4(2) motif. They are arranged into a two-dimensional polymeric structure parallel to (10) in which the water mol­ecule is a single donor and a double acceptor, whereas the amino group is a double donor and a single acceptor in the hydrogen bonding. These two-dimensional assemblies alternate with the layers of phenazine mol­ecules arranged into a herringbone motif. Each phenazine mol­ecule is hydrogen bonded to two water mol­ecules and thus a three-dimensional framework of hydrogen-bonded mol­ecules is generated

Quinoxaline–3-amino­phenol–water (2/1/2)

The asymmetric unit of the title compound, 2C8H6N2·C6H7NO·2H2O, contains two quinoxaline mol­ecules, one mol­ecule of 3-amino­phenol and two water mol­ecules which are hydrogen bonded to form a two-dimensional polymeric structure. Each of the symmetry-independent quinoxaline mol­ecules forms separate stacks of different symmetry. In one set of stacks, the mol­ecules are related by a screw axis and are slightly tilted [dihedral angle = 7.12 (1)°]. In the second set of stacks, adjacent mol­ecules are parallel and related by an inversion center [inter­planar distances = 3.376 (4) and 3.473 (4) Å]

Bis(4,6-diaminopyrimidin-2-yl) disulfide dimethyl sufoxide disolvate

The title compound, C8H10N8S2·2C2H6SO, was obtained unintentionally during an attempt to prepare a thiol-ate derivative of trimethyl-tin. The complete disulfide mol-ecule is generated by twofold rotation symmetry and the C - S - S - C torsion angle around the S - S bond is -85.70 (10)°. The mol-ecules are connected via N - H⋯N hydrogen bonds into strongly corrugated layers parallel to (001), generating an R 2 2(8) motif. The solvent mol-ecule, which exhibits minor disorder of its S atom [site occupancies = 0.9591 (18) and 0.0409 (18)], is linked to this layer via a pair of N - H⋯O inter-actions

5-Amino-1-naphthol

In the title compound, C10H9NO, the amino and the hydr­oxy groups act both as a single donor and a single acceptor in hydrogen bonding. In the crystal, mol­ecules are connected via chains of inter­molecular ⋯N—H⋯O—H⋯ inter­actions, forming a two-dimensional polymeric structure resembling the hydrogen-bonded mol­ecular assembly found in the crystal structure of naphthalene-1,5-diol. Within this layer, mol­ecules related by a translation along the a axis are arranged into slipped stacks via π–π stacking inter­actions [inter­planar distance = 3.450 (4) Å]. The amino N atom shows sp 3 hybridization and the two attached H atoms are located on the same side of the aromatic ring

5-Methyl-3,6,7,8a-tetra­hydro-2H-diimidazo[1,2-c:1′,2′-e]pyrido[1,2-a][1,3,5]triazin-5-ium iodide

The structure of the title compound, C12H16N5 +·I−, shows that the methyl­ation reaction with CH3I occurred at the imine N atom at position 5 of the 3,6,7,8a-tetra­hydro-2H-diimidazo[1,2-c:1′,2′-e]pyrido[1,2-a][1,3,5]triazine system. In the cation, the sp 3-hybridized C atom belonging to the fused dihydro­pyrine and dihydro-1,3,5-triazine rings deviates by 0.514 (3) Å from the best plane defined by the remaining cationic non-H atoms. The fused dihydro­pyridine and dihydro-1,3,5-triazine rings are each in a half-chair conformation with the sp 3-hybridized C atom as a flap. The iodide anion is 3.573 (2) Å from the methyl­ated N atom and exhibits five short C—H⋯I− contacts with distances less than 3.16 Å. The structure has been determined from a non-merohedral twin with twin law [−1 0 0 0 − 1 0 0.115 0 1], minor domain = 0.1559 (12)

A third polymorph of N,N′-bis­(pyridin-2-yl)benzene-1,4-diamine

A third polymorph of the title compound, C16H14N4, has been obtained. The mol­ecule adopts a non-planar conformation with an E configuration at the two partially double exo C N bonds of the 2-pyridyl­amine units. Like in the triclinic form [Bensemann et al. (2002 ▶). New J. Chem. 26, 448–456], the recognition process between 2-pyridyl­amine units takes place through formation of a cyclic R 2 2(8) hydrogen-bond motif, leading to the creation of tapes parallel to [001]

(Carbonato-κ2 O,O′)bis­(di-2-pyridyl­amine-κ2 N,N′)cobalt(III) bromide

In the title compound, [Co(CO3)(C10H9N3)2]Br, a distorted octa­hedral coordination of the CoIII atom is completed by four N atoms of the two chelating di-2-pyridyl­amine ligands and two O atoms of the chelating carbonate anion. The di-2-pyridyl­amine ligands are nonplanar and the dihedral angles between the 2-pyridyl groups are 29.11 (9) and 37.15 (12)°. The coordination cation, which has approximate C 2 symmetry, is connected to the bromide ion via an N—H⋯Br− hydrogen bond. The ionic pair thus formed is further assembled into a dimer via N—H⋯O inter­actions about an inversion centre. A set of weaker C—H⋯O and C—H⋯Br− inter­actions connect the dimers into a three-dimensional network

Synthesis, Structure and Biological Activity of Novel 4,5-dihydro-1H-imidazol-2-yl-phthalazine Derivatives and Their Copper(II) Complexes

As a continuation of our previous investigations aimed at the synthesis of novel nitrogen-containing heterocycles and their metal complexes, we have now prepared two series of compounds incorporating a phthalazine ring at the position C2 of 4,5-dihydro-1H-imidazole. The starting phthalazine (I) in the reaction with 2-chloroimidazoline (II) gives rise to the formation of pseudobase III. Then, compound III upon treatment with HOSA yields betaine which under basic conditions gives 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (IV). In turn, the reactions of compound IV with a variety of acyl and sulfonyl chlorides lead to the formation of benzamides (V) and benzenesulfonamides (VI). Moreover, compounds V and VI can be transformed into corresponding 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one derivatives VII and VIII. Such ligands are susceptible to the reaction with CuCl2 giving rise to the formation of corresponding copper(II) complexes: dichloro[2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine]copper(II) (1), dichloro[2-(1-benzoyl-4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one]copper(II) (2) and dichloro{bis-[2-(1-(phenylsulfonyl)-4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-one]}copper(II) (3). The most promising results of biological studies were obtained for complex 1 towards the HeLa cell line (IC50 = 2.13 μM) without a toxic effect against fibroblasts BALB/3T3 (IC50 = 135.30 μM), which pointed towards its selectivity as a potential antitumor agent. It should be pointed out, that corresponding free ligand 2-(4,5-dihydro-1H-imidazol-2-yl)phthalazin-1(2H)-imine (IV) was less active than its metal complex (IC50 = 87.74 μM)

Circulatory Activities of Some 2-Imidazoline Derivatives in Wistar Rats

Wstęp Pochodne 2-imidazoliny stanowią ważną grupę leków przeciwnadciśnieniowych o ośrodkowym mechanizmie działania. Celem pracy było otrzymanie wielu analogów znanych imidazolin typu klonidyny i lofeksydyny, zbadanie ich struktury oraz określenie wpływu na ciśnienie tętnicze krwi i częstość akcji serca szczurów szczepu Wistar. Materiał i metody Oznaczenie wpływu analogów a-hydroksylowych (1a-g) i 2-aminowych (2a-d) 2-aryloiminoimidazolin oraz N-benzylo-N-(4,5-dihydro- -1H-imidazol-2-ylo)-metoksyloaminy (3) na średnie ciśnienie tętnicze krwi i częstość akcji serca prowadzono na szczurach normotensywnych, samcach rasy Wistar o masie 220–370 g. Pomiarów ciśnienia skurczowego krwi dokonywano metodą krwawą. Rejestrowano odpowiedź presyjną na każdorazową podaną dawkę związku imidazoliny. Pomiar częstości akcji serca u szczurów wykonywano, zliczając wychylenia słupa krwi tętniczej w jednostce czasu. Wychylenia rejestrowano poprzez dotętniczą kaniulę polietylenową (liczba wychyleń/min). Wyniki Wykazano zróżnicowany i zależny od struktury wpływ badanych pochodnych 2-imidazoliny na ciśnienie tętnicze krwi i częstość akcji serca po podaniu dożylnym. W grupie połączeń hydroksyloaminy największą aktywność wykazał związek 1b, zawierający grupę metylową w pozycji 4 pierścienia fenylowego (ED50 = 0,17 mg/kg). Pochodne o-fenylenodiaminy typu 2, w zależności od charakteru lipofilowego, działały hipo- (2a i 2b) lub hipertensyjnie (2c i 2d). Na podstawie badania rentgenograficznego tiocyjanianu 2e wykazano, iż związki te posiadają cechy strukturalne odpowiadające ligandom receptorów a2-adrenergicznych. Natomiast analog lofeksydyny (3), zawierający ugrupowanie N-metoksylowe w łańcuchu bocznym, okazał się nieaktywny w dawkach sięgających 2 mg/kg. Wnioski Przyłączenie grupy hydroksylowej do egzocyklicznego atomu 2-aryloiminoimidazolin nie pozbawia tych związków działania hipotensyjnego. Działanie analogów zawierających grupę aminową w położeniu 2 pierścienia aromatycznego zależy od ich charakteru lipofilowego. Można przypuszczać, iż większa lipofilowość pochodnych 2c i 2d w porównaniu z 2a i 2b umożliwia tym związkom przenikanie bariery krew-mózg i blokowanie ośrodkowych receptorów a2-adrenergicznych, co objawia się działaniem hipertensyjnym.Background 2-aryliminoimidazolines constitute a valuable class of centrally acting antihypertensive drugs. The aim of our studies was to evaluate effects of some analogues of clonidine and lofexidine on the arterial blood pressure and heart rate in Wistar rats following i.v. administration. Material and methods Effects of a-hydroxy (1a-g) and 2-amino (2a-d) analogues of clonidine and N-benzyl-N- -(4,5-dihydro-1H-imidazol-2-yl)-methoxylamine (3) on the mean arterial blood pressure and heart rate were determined in normotensive, male Wistar rats weighting 220–370 g. The experiments were performed using animals anaesthetized with urethane and tracheotomized. Results Compounds 1a-g showed hypotensive activity accompained by a positive chronotropic effect with 1b being the most active (ED50 = 0,17 and 0,145 mg/kg respectively). Among the 2-amino-phenyliminoimidazolines of type 2, the more hydrophilic 2a and 2b exhibited relatively weak hypotensive effects, while the more hydrophobic analogues 2c and 2d were shown to possess remarkable hypertensive activities at doses 0,25 mg/kg. X-ray crystal structure analysis of the thiocyanate salt 2e confirmed geometrical features required for good ligand interaction at the a2-adrenergic receptors. On the other hand, N-benzyl-N-(4,5-dihydro-1H-imidazol-2-yl)-methoxylamine 3was not active at doses up to 2 mg/kg. Conclusions The introduction of the hydroxyl group on the exocyclic nitrogen atom of 2-aryliminoimidazolines afforded compounds retaining much of the hypotensive activity. On the other hand, cardiovascular activity of the analogues containing 2-amino substituent at the phenyl ring depends strongly on their lipophilic character. It can be presumed that penetration of the more lipophilic 2c and 2d into the CNS enables these compounds to block a2-adrenergic receptors which results in an increased blood pressure