Synthesis of 1-(2-Carboxyethylbenzyl)-2-benzenesulfonamidobicyclo[2.2.1]heptane: A Novel Potent Thromboxane Antagonist

A potent thromboxane antagonist, 1-[2-(2-carboxyethyl)benzyl)]-2-benzenesulfonamidobicyclo-[2.2.1]heptane was synthesized from norcamphor in 8 steps. It was shown to be a very potent thromboxane antagonist by inhibition of platelet aggregation induced by U46,619 at nanomolar concentration. The key intermediate 3-[2-bromomethylphenyl]propyl tetrahydropyran ether may be useful for the synthesis of other interphenylene containing prostaglandin analogs.     

Synthesis of 2‐[4‐(Imidazolin‐2‐Ylideneamino)Benzyl]‐Indan‐1‐Ones as Novel Potent Prostacyclin Antagonists

Prostacyclin is involved in many pathological conditions, such as sensitization of inflammation induced pain and isovolumetic distention. Therefore, antagonism of prostacyclin action may be useful in the alleviation of these conditions. In this study, novel potent prostacyclin antagonists, 2‐[4‐(imidazolin‐2‐ylideneamino)benzyl]‐indan‐1‐ones were synthesized from their respective substituted indanones in three steps. The construction of the amino‐imidazole moiety of these derivatives is achieved by using in situ generation of chloro‐imidazole and reaction with their respective anilines. Thus, these N‐substituted 2‐imidazolines can be prepared safely and efficiently. Moreover, these compounds show potent prostacyclin antagonistic activity by inhibition of prostacyclin agonist induced ERK_1/2 phosphorylation in human erythroleukemia cells. Moreover, we observed an increase in activity with the increase in electro‐donating property of the substitution on the indanone aromatic ring. Prostacyclin antagonists with increased potency may be designed based on these findings. These compounds may also be invaluable tools for the study of the physiological functions of prostacyclin.     

Hydrogen bonding in dibromo[2‐(dimethyl­aminomethyl)phenyl][2‐(dimethylammoniomethyl)phenyl]tin(IV) tetra­bromo­[2‐(dimethyl­aminomethyl)phenyl]­tin(IV)

The mol­ecular structure of the title compound, [SnBr₂(C₉H₁₂N)(C₉H₁₃N)][SnBr₄(C₉H₁₂N)], consists of a dibromo­bis[2‐(dimethyl­aminomethyl)phenyl][2‐dimethylammoniomethyl)phenyl]tin(IV) cation and a tetra­bromo­[2‐(dimethyl­aminomethyl)phenyl]tin(IV) anion. As a result of strong intra­molecular N→Sn inter­actions, distorted trigonal–bipy­ramidal and octa­hedral coordination geometries are established for the metal centres of the diorganotin(IV) and monoorganotin(IV) fragments, respectively. The cation and anion are linked together by two Br⋯H contacts, while three additional similar contacts result in a dimeric fragment which repeats in a two‐dimensional supra­molecular arrangement.     

Supramolecular Architectures of Four New Transition Metal Complexes with 3‐[4‐(Carboxymethoxy)phenyl]propanoic Acid and N‐[4‐(Carboxymethoxy)phenyl]iminodiacetic Acid

Four new transition metal complexes: [Cu(Hcppa)₂(H₂O)₂] ( 1 ), [Co₂(cppa)₂(H₂O)₁₀] ( 2 ), [Co₃(cpia)₂(H₂O)₈] · 2H₂O ( 3 ) and [Ni₃(cpia)₂(H₂O)₁₂] · 6H₂O ( 4 ) {H₂cppa = 3‐(4‐(carboxymethoxy)phenyl]propanoic acid; H₃cpia = N‐[4‐(carboxymethoxy)phenyl]iminodiacetic acid} were synthesized and characterized. Complexes 1 and 2 show mononuclear structures, complexes 3 and 4 exhibit dinuclear structures. All complexes extend to 3D supramolecular networks through hydrogen bonds, of which complexes 3 and 4 display microporous structures. In complexes 2 – 4 the water clusters are trapped by the cooperative association of coordinate interactions as well as hydrogen bonds, forming different 1D metal‐water chain structures. Thermal stabilities of complexes 1 – 4 were discussed.     

Design and Synthesis of 3‐Aryl‐5‐Alicylic‐[1,2,4]‐oxadiazoles as Novel Platelet Aggregation Inhibitors

A series of 4‐[2‐(alicyclic‐[1,2,4]oxadiazol‐3‐yl)phenoxy]‐butyric acids were synthesized from N‐hydroxy‐2‐isopropoxy benzamidine in 4 steps with good yields. These [1,2,4]oxadiazoles are novel platelet aggregation inhibitors preventing human platelet aggregation induced by thromboxane derivative U44,619 and adenosine diphosphate. A structure‐activity‐relationship study revealed that the potency for these 5‐oxadiazoles increases with the increase in the ring size of the alicylic rings. Derivative 8f may be useful as a template for the design of more potent anti‐platelet agents.     

Similarities and differences between bis[2‐(bromomethyl)phenyl] diselenide,bis[2‐(chloromethyl)phenyl] diselenide and bis[2‐(hydroxymethyl)phenyl] diselenide

The title compounds, C₁₄H₁₂Br₂Se₂, (I), C₁₄H₁₂Cl₂Se₂, (II), and C₁₄H₁₄O₂Se₂, (III), feature a diselenide bridge between two o‐benzyl bromide [in (I)], two o‐benzyl chloride [in (II)] or two o‐benzyl alcohol units [in (III)]. In the molecular structure of (I) and in both independent molecules of (II), close contacts are observed between the halogen centres and the diselenide unit. In the case of modification (IIIa), strong hydrogen bonds between the –OH groups dominate, whereas the molecular structures of modification (IIIb) and bis{2‐[(dimethylamino)methyl]phenyl} diselenide, C₁₈H₂₄N₂Se₂, (IV), are comparable with those of (I) and (II). A correlation between the strength of the contacts and the angle between the benzene planes and the Se—Se units is found.     

4‐[3‐(3,4‐Di­methoxy­phenyl)­prop‐2‐enoyl]­phenyl methacryl­ate and 4‐[3‐(2‐bromo­phenyl)­prop‐2‐enoyl]­phenyl methacryl­ate

Chalcones (α,β‐unsaturated ketones) are effective antitumour agents. It has been proved that having halogen or methoxy groups substituted in various positions of the phenyl ring enhances the activity of chalcones many times. The title compounds, C₂₁H₂₀O₅ and C₁₉H₁₅BrO₃, respectively, were chosen for crystallographic study in order to determine their structures and conformations. In both compounds, the keto group is in the s‐cis conformation and is almost planar. There are weak intramolecular interactions in both structures.     

Synthesis of Novel 3‐(3‐(5‐Methylisoxazol‐3‐yl)‐7H‐[1,2,4]Triazolo [3,4‐b][1,3,4]Thiadiazin‐6‐yl)‐2H‐Chromen‐2‐Ones

A novel series of coumarin substituted triazolo‐thiadiazine derivatives were designed and synthesized by using 5‐methyl isoxazole‐3‐carboxylic acid ( 1 ), thiocarbohydrazide ( 2 ), and various substituted 3‐(2‐bromo acetyl) coumarins ( 4a , 4b , 4c , 4e , 4d , 4f , 4g , 4h , 4i , 4j ). Fusion of 5‐methyl isoxazole‐3‐carboxylic acid with thiocarbohydrazide resulted in the formation of the intermediate 4‐amino‐5‐(5‐methylisoxazol‐3‐yl)‐4H‐1,2,4‐triazole‐3‐thiol ( 3 ). This intermediate on further reaction with substituted 3‐(2‐bromo acetyl) coumarins under simple reaction conditions formed the title products 3‐(3‐(5‐methylisoxazol‐3‐yl)‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl‐2H‐chromen‐2‐ones ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j ) in good to excellent yields. All the synthesized compounds were well characterized by physical, analytical, and spectroscopic techniques.     

4‐Methyl‐N‐[2‐(p‐tolylsulfanyl)phenyl]benzene­sulfonamide

The title compound, C₂₀H₁₉NO₂S₂, is formed by a palladium–copper‐catalyzed reaction between 4‐methyl‐N‐[2‐(prop‐2‐ynyl­sul­fanyl)­phenyl]­benzene­sul­fon­amide and p‐iodo­toluene. The mol­ecules contain three essentially planar parts, namely an amino­thio­phenol moiety (A), a toluene­sulfone moiety excluding the oxo ligands (B) and a tolyl group (C), approximately orthogonal to each other; the dihedral angles A/B, A/C and B/C are 111.6 (1), 89.3 (1) and 101.4 (1)°, respectively. Intermolecular N—H?O hydrogen bonds link the mol­ecules into infinite one‐dimensional chains.     

A Novel and Facile Synthesis of 2‐(Benzofuran‐2‐yl)benzo[h]quinoline‐3‐carboxylic Acid Derivatives

A simple and concise approach for the synthesis of a series of new heterocyclic systems of 2‐(benzofuran‐2‐yl)benzo[h]quinoline‐3‐carboxylic acid derivatives ( 3a–3g ) is described. The synthetic strategy features the one‐pot reaction of ethyl 2‐(chloromethyl)benzo[h]quinoline‐3‐carboxylate ( 2 ) with various substituted salicylaldehydes as well as 2‐hydroxy‐1‐naphthaldehyde as a key step. The substrate 2 was prepared in good yield by a mild, efficient and direct reaction of 1‐naphthylamine ( 1 ) with Vilsmeier‐Haack reagent. The structures of all the new compounds were identified by spectral data and elemental analysis.     

3‐[4‐(4‐Fluoro­phenyl)­piperazin‐1‐yl­methyl]‐5‐methyl‐1,3‐benzoxazol‐2(3H)‐one and 3‐[4‐(2‐fluoro­phenyl)­piperazin‐1‐yl­methyl]‐5‐methyl‐1,3‐benzoxazol‐2(3H)‐one

The title compounds, both C₁₉H₂₀FN₃O₂, contain essentially planar benzoxazolinone ring systems, within which the C—N bond distances and angles do not differ significantly between the two compounds. In both cases, the piperazine ring adopts an almost perfect chair conformation and the benzoxazo­l­inone ring system lies nearly perpendicular to it. The structures contain intermolecular C—H⋯O contacts, and the interactions between the benzoxazolinone and fluoro­phenyl­piperazine portions of the mol­ecules are segregated.     

3‐(2‐Furyl)‐6‐(4‐methyl­phenyl)‐7H‐1,2,4‐triazolo­[3,4‐b][1,3,4]thia­diazine and its 6‐phenyl analogue

In the title compounds, C₁₅H₁₂N₄OS, (I), and C₁₄H₁₀N₄OS, (II), the thia­diazine ring adopts a skew‐boat conformation, while the triazole and furyl rings are essentially planar. The phenyl group is twisted by 33.5 (2) and 47.9 (1)° out of the triazole‐ring plane in (I) and (II), respectively.     

On triazoles XLIX. Synthesis of 5,6‐dihydrothiazolo[3,2‐b]‐[1,2,4]triazol‐2‐yl‐, 6,7‐dihydro‐5H‐[1,2,4]triazolo[5,1‐b][1,3]thiazin‐2‐yl‐, and 5,6,7,8‐tetrahydro[1,2,4]triazolo[5,1‐b] [1,3]thiazepin‐2‐yl‐isoquinolinium salts

5′‐Mercapto‐1′H‐1,2,4‐triazol‐3′‐yl‐isoquinolinium salts (6) were synthesised by the reaction of ortho‐acyl phenylacetones (2) or the corresponding pyrylium salts (3) and 5‐amino‐2,3‐dihydro‐1H‐1,2,4‐triazole‐3‐thione (5) . Treatment of thioles 6 withα,ω‐dibromoalkanes led to type 15, 16 and 17 isoquinolinium salts condensed with thiazole, thiazine and thiazepine rings. When 6 are reacted with dibromomethane (10) 11 type dimeric structures are obtained.     

Bis[μ‐2‐({2‐[2‐(2‐chlorophenoxy)‐1‐oxidoethylidene]hydrazinylidene}methyl)phenolato]bis[pyridinecopper(II)] methanol disolvate

In the title compound, [Cu₂(C₁₅H₁₁ClN₂O₃)₂(C₅H₅N)₂]·2CH₃OH, the coordination geometry of the metal centre can be described as square pyramidal. Pairs of pentacoordinated metal centres are bridged by symmetry‐related phenolate O atoms about the inversion centre at (, 0, ), resulting in a binuclear metal cluster via edge‐sharing.     

A two‐dimensional undulating AgI coordination polymer constructed of Ag—C and Ag—O bonds: poly[[[μ3‐(5,6‐η):κO2:κO2‐(±)‐(1S,2S,3R,4R)‐3‐carboxy‐7‐oxabicyclo[2.2.1]hept‐5‐ene‐2‐carboxylato]silver(I)] monohydrate]

The title coordination polymer, {[Ag(C₈H₇O₅)]·H₂O}_n, is built from Ag⁺ cations and singly protonated dehydronorcantharidin (SP‐DNC) anions, with a distorted trigonal‐planar geometry at the metal centre. The coordination number of Ag^I is three (with one Ag—π bond and two Ag—O bonds, one from each of three different SP‐DNC ligands), if only formal Ag–ligand bonds are considered, but can be regarded as five if longer weak Ag...O interactions are also included. The two‐dimensional corrugated‐sheet coordination polymer forms a non‐interpenetrating framework with (4.8²) topology. Disordered water molecules are sandwiched between the sheets.     

Synthesis,characterization and polymerization of the novel carbazole‐based monomer 9‐(bicyclo[2.2.1]hept‐5‐en‐2‐ylmethyl)‐9H‐carbazole

Synthesis and characterization of a novel carbazole‐based monomer, 9‐(bicyclo[2.2.1]hept‐5‐en‐2‐ylmethyl)‐9H‐carbazole (BHMCZ) and its copolymerization with ethylene by using two metallocene/MAO catalyst systems are presented. The monomer was characterized by means of NMR spectroscopy, MS and elementary analysis. Copolymerization studies were conducted using [Ph₂C(Ind)(Cp)ZrCl₂] and [Ph₂C(Flu)(Cp)ZrCl₂] catalysts. The [Ph₂C(Ind)(Cp)ZrCl₂] catalyst gave a copolymer containing as much as 4.6 mol‐% of BHMCZ. Polymers were characterized using NMR spectroscopy, gel permeation chromatography (GPC) and differential scanning calorimetry (DSC).     

Bis[4‐(3‐pyridylmethyl­eneamino)­phenyl]methane

In the title Schiff base compound, C₂₅H₂₀N₄, the two rigid parts adopt an angular conformation, thus making the compound a potential non‐linear ditopic ligand for the construction of interesting coordination polymers.     

Crystallographic report: 1‐[4‐(2‐Thienyl)phenyl]germatrane

In the title compound, germanium is penta‐coordinated and adopts a trigonal bipyramidal geometry. The (2‐thienyl)phenyl group and the nitrogen atom each occupy an apical position with a transannular N→Ge bond distances of 2.247(4) and 2.219(4) Å for the two independent molecules. Copyright © 2005 John Wiley & Sons, Ltd.