Discovery of two new classes of potent monoamine oxidase-B inhibitors by tricky chemistry.

The discovery of potent and selective monoamine oxidase-B inhibitors for the management of neurodegenerative diseases such as Alzheimer's and Parkinson's diseases is still a challenging endeavor. Herein, we report the discovery of two new classes of potent and selective MAO-B inhibitors based on chromane-2,4-dione and chromone-3-carboxamide scaffolds.

4-(4-Chlorophenyl)-3,7,7-trimethyl-1-[2-(4-nitrobenzoyl)ethyl]-4,7,8,9-tetrahydro-1H-pyrazolo[3,4-b]quinolin-5(6H)-one-ethanol (1/1).

Molecules of the title compound, C(28)H(27)ClN(4)O(4).C(2)H(6)O, form a C(6) chain via an N--H...O hydrogen bond along the c axis by the operation of a c-glide plane, with N...O = 2.761 (3) A and N--H...O = 165 degrees. The molecules are further linked by a weak C--H...O interaction, with C.O = 3.344 (4) A and C--H...O = 150 degrees. Pendant hydrogen-bonded ethanol solvent molecules are attached to the chains by O--H...N hydrogen bonds, with O...N = 2.904 (3) A and O--H...N = 175 degrees.

Hydrogen bonding in C-methylated nitroanilines: a room-temperature monoclinic polymorph of 4-methyl-3-nitroaniline with Z' = 2.

The title compound, C(7)H(8)N(2)O(2), is monoclinic (space group P2(1)/n) at 295 (2) K with Z' = 2. The two types of molecule form independent C(7) chains, and the structure is related to that of the low-temperature triclinic polymorph, where Z' = 4 in P1, by a simple displacive transformation.

Hydrogen bonding in nitroaniline analogues: a three-dimensional framework in 2-amino-6-nitro-1,3-benzothiazole.

In the title compound, C(7)H(5)N(3)O(2)S, the molecules are linked into a three-dimensional framework by a combination of a three-centre N-H...(O)(2) hydrogen bond, and two-centre N-H...N and C-H...O hydrogen bonds.

4-Iodo-2-methyl-5-nitroaniline exhibits neither strong hydrogen bonding nor intermolecular I...nitro interactions.

In the title compound, C(7)H(7)IN(2)O(2), the O atoms of the nitro group are disordered over two sets of sites and there is evidence that the intramolecular I...nitro interaction is repulsive. In the crystal structure, there are neither strong hydrogen bonds, nor intermolecular I...nitro interactions, nor aromatic pi-pi-stacking interactions.

Ethyl 6-amino-2-methoxypyridine-3-carboxylate, interplay of molecular and supramolecular structure.

The title compound, C(9)H(12)N(2)O(3), crystallizes with two molecules in the asymmetric unit. There is extensive hydrogen bonding which results in the formation of a two-dimensional corrugated sheet. This supramolecular structure is determined by the formation of hydrogen-bonded chains resulting from the presence of a 6-amino group and an ethoxycarbonyl group as substituents on a pyridine ring in relative para positions which constitute a pi-electron 'push-pull' system.

[6-Amino-3-methyl-5-nitrosopyrimidine-2,4(1H,3H)-dionato]-sodium dihydrate at 150 K: coordination-polymer ladders linked by hydrogen bonds.

In the title compound, [Na(C(5)H(5)N(4)O(3))].2H(2)O, each Na cation is linked to three C(5)H(4)N(4)O(3)(-) anions and two water molecules, forming approximately octahedral NaNO(5) units; the cations and the anions form molecular ladders, and each ladder is linked to four neighbouring ladders by O-H...O and O-H...N hydrogen bonds.

Triclinic and orthorhombic polymorphs of 2-iodo-4-nitroaniline: interplay of hydrogen bonds, nitro...I interactions and aromatic pi-pi-stacking interactions.

In the triclinic polymorph of 2-iodo-4-nitroaniline, C(6)H(5)IN(2)O(2), space group P-1, the molecules are linked by paired N-H...O hydrogen bonds into C(8)[R(2)(2)(6)] chains of rings. These chains are linked into sheets by nitro...I interactions, and the sheets are pairwise linked by aromatic pi-pi-stacking interactions. In the orthorhombic polymorph, space group Pbca, the molecules are linked by single N-H...O hydrogen bonds into spiral C(8) chains; the chains are linked by nitro...O interactions into sheets, each of which is linked to its two immediate neighbours by aromatic pi-pi-stacking interactions, so producing a continuous three-dimensional structure.

Hydrogen-bonded chains in N-(2-nitrophenyl)phenylamine.

Molecules of the title compound, C(12)H(10)N(2)O(2), are markedly non-planar. There is an intramolecular N-H...O hydrogen bond, and the molecules are linked into zigzag chains by a single C-H...O hydrogen bond. Comparisons are made with the supramolecular aggregation in isomeric amino-nitro derivatives, and in some N-methylnitroanilines.

N,N'-Bis[tris(hydroxymethyl)methyl]-ethanediamide: six O-H...O hydrogen bonds generate only a two-dimensional structure.

Molecules of the title compound, C(10)H(20)N(2)O(8), adopt a conformation which is almost centrosymmetric. The molecules are disordered over two sets of sites with an occupancy ratio of 0.94:0.06. In the major form, there are two intramolecular O-H...O hydrogen bonds [O...O 2.756 (4) and 2.765 (4) A; O-H...O 144 and 146 degrees ], in which the two amidic O atoms act as acceptors. In addition, there are four intermolecular O-H...O hydrogen bonds [O...O 2.650 (3)-2.666 (3) A; O-H...O 158-171 degrees ]; these link each molecule to six others in a continuous sheet structure which contains five distinct ring motifs, two of the S(7) type, two of the R(3)(3)(10) type and one of the R(2)(2)(22) type.

Bis[N-(6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxypyrimidin-2-yl)glycyl-glycinato]triaquacalcium: coordination polymer chains linked by hydrogen bonds.

In the title compound, [Ca(C9H11N6O5)2(H2O)3], the Ca atom lies on a twofold rotation axis in C2/c and the three water molecules are all disordered, each over two sites having equal occupancy. The anion acts as a bridging ligand between pairs of Ca sites on the same twofold axis, thus forming a one-dimensional coordination polymer, with the chains lying along the twofold axes. These chains are linked by multiple O-H...O and N-H...O hydrogen bonds into a single three-dimensional framework.

Solvated and solvent-free forms of N,N'-dithiodiphthalimide.

N,N'-Dithiodiphthalimide, C16H8N2O4S2, crystallizes from ethyl acetate with two independent molecules in the asymmetric unit, in which the N-S-S-N torsion angles are -83.59 (19) and 92.9 (2) degrees. The molecules are linked by C-H...O hydrogen bonds and aromatic pi-pi-stacking interactions into a three-dimensional framework. When crystallized from either dichloromethane or ethanol, solvates are formed in which the molecules of the title compound lie across twofold rotation axes in space group C2/c, with N-S-S-N torsion angles of 93.54 (7) and 96.14 (11) degrees. There are no hydrogen bonds in these solvates, but the molecules are linked by aromatic pi-pi-stacking interactions into chains, between which there are continuous channels. Disordered solvent molecules occupy these channels, which account for ca 20% of the unit-cell volume.

[N-(6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxopyrimidin-2-yl)-glycylglycinato]aquapotassium, a three-dimensional coordination polymer.

In the title compound, polymeric potassium N-(6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxopyrimidin-2-yl)glycylglycinate hydrate, (K(+).C(9)H(11)N(6)O(5)(-).H(2)O)(n), the hexacoordinate K(+) cation is linked to five different anions as well as to the water molecule, with K-O distances in the range 2.617 (2)-2.850 (2) A. Four of the O atoms in each anion coordinate to K centres, one of them acting as a bridging ligand, leading to the formation of nearly square centrosymmetric K(2)O(2) rings. The structure is analysed in terms of (010) metal-ligand sheets linked by [010] chains of fused rings.

Methyl 4-amino-2,3-dihydro-6-methoxy-1,3-dioxo-1H-pyrrolo[3,4-c]-pyridine-7-carboxylate forms hydrogen-bonded sheets built from R2(2)(8) and R6(6)(42) rings.

In the title compound, C10H9N3O5, which was formed by the reaction of 6-amino-2-methoxy-4(3H)-pyrimidinone with dimethyl acetylenedicarboxylate, the molecules are linked by N-H...O hydrogen bonds [N...O 2.8974 (15) and 3.0300 (15) A, and N-H...O 165 and 174 degrees] into planar sheets built from alternating R2(2)(8) and R6(6)(42) rings.

Soft C-H.O hydrogen bonds in methyl 2,4-dinitrobenzenesulfenate: sheets built from R22(10) and R66(42) rings.

Molecules of the title compound, C(7)H(6)N(2)O(5)S, are linked into sheets containing R(2)(2)(10) and R(6)(6)(42) rings by C-H.O hydrogen bonds [C.O 3.405 (3) and 3.511 (2) A; C-H.O 159 and 169 degrees ], in which both acceptors are in the same nitro group. Comparisons are made with the hydrogen bonding in other nitrobenzenesulfenate esters.

N-(2-Amino-1,6-dihydro-5-nitroso-6-oxopyrimidin-4-yl)-L-isoleucine-water (4/1): interplay of molecular and supramolecular structures.

In the title compound, 2C10H15N5O4-0.5H2O, there are two independent molecules of the pyrimidinylisoleucine in general positions and a water molecule lying on a twofold rotation axis. The bond lengths within the organic moieties demonstrate significant polarization of the electronic structure. Each of the organic molecules participates in 12 intermolecular hydrogen bonds, of O-H...O and N-H...O types, while the water molecule acts as a double donor and as a double acceptor of O-H...O hydrogen bonds. The organic components are linked by the hydrogen bonds into a single three-dimensional framework, reinforced by the water molecules.

Methyl 7-hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropteridine-6-carboxylate-dimethyl sulfoxide (1/1) forms chains containing O-H...O and C-H...O hydrogen bonds and aromatic pi-pi-stacking interactions.

In the title compound, C11H12N4O5-C2H6OS, the molecular components are linked by a short hydrogen bond with dimensions O...O 2.517 (2) A and O-H...O 168 degrees. Paired C-H...O hydrogen bonds [C...O 3.362 (2) and 3.382 (2) A; C-H...O 157 and 140 degrees] generate cyclic centrosymmetric four-component aggregates reinforced by aromatic pi-pi-stacking interactions, and further C-H...O hydrogen bonds [C.O 3.472 (3) and 3.521 (2) A; C-H...O 156 and 157 degrees] link these aggregates into chains.

Hydrated metal complexes of N-(6-amino-3,4-dihydro-3-methyl-5-nitroso-4-oxopyrimidin-2-yl)glycinate: interplay of molecular, molecular-electronic and supramolecular structures.

The title anion, (C(7)H(8)N(5)O(4))(-), L(-), forms hydrated metal complexes with a range of metal ions M(+) and M(2+). Lithium and manganese(II) form finite molecular aggregates [Li(L)(H(2)O)(3)] (1) and [Mn(L)(2)(H(2)O)(4)].6H(2)O (4) in which the molecular aggregates are linked into three-dimensional frameworks by extensive hydrogen bonding. The sodium and potassium derivatives, [Na(2)(L)(2)(H(2)O)(3)] (2) and [K(L)(H(2)O)] (3) both form organic-inorganic hybrid sheets in which metal-oxygen ribbons are linked by strips containing only organic ligands: these sheets are linked by hydrogen bonds into three-dimensional frameworks. In (2) the metal-oxygen ribbon is built from pairs of edge-shared trigonal bipyramids linked by water molecules, while in (3) it consists of a continuous chain of vertex-sharing octahedra. The nitroso group in the anion acts as an eta(1) ligand towards Na(+) and as an eta(2) ligand towards K(+). In all cases the anion L(-) shows the same unusual pattern of interatomic distances as the neutral parent LH.

Hydrogen bonding in substituted nitroanilines: isolated nets in 1,3-diamino-4-nitrobenzene and continuously interwoven nets in 3,5-dinitroaniline.

Molecules of 1,3-diamino-4-nitrobenzene, C(6)H(7)N(3)O(2), are linked by N-H.O hydrogen bonds [N.O 2.964 (2) and 3.021 (2) A; N-H.O 155 and 149 degrees] into (4,4) nets. In 3,5-dinitroaniline, C(6)H(5)N(3)O(4), where Z' = 2, the molecules are linked by three N-H.O hydrogen bonds [N.O 3.344 (2)-3.433 (2) A and N-H.O 150-167 degrees] into deeply puckered nets, each of which is interwoven with its two immediate neighbours.

Hydrogen bonding in C-methylated nitroanilines: the three-dimensional framework structure of 2-methyl-4-nitroaniline.

Molecules of 2-methyl-4-nitroaniline, C(7)H(8)N(2)O(2), act as double donors and as double acceptors of N--H...O hydrogen bonds [N...O 3.117 (3) and 3.239 (3) A; N--H...O 169 and 136 degrees ]. The molecules are thereby linked into a three-dimensional framework.