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SULFONAMIDE DERIVATIVES, THEIR PRODUCTION AND USE

The present invention provides compounds which specifically inhibit FXa, which are effective when orally administered and which are useful as a safe medicine for the prevention or treatment of diseases caused by thrombus or infarction.Compounds of this invention are piperazinones of the formula: wherein R 1 is an optionally substituted hydrocarbon group or an optionally substituted heterocyclic group; the ring A is an optionally substituted divalent nitrogen-containing heterocyclic group, in addition to being substituted by the group of the formula: and the group of the formula: Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent heterocyclic group; X is a direct bond or an optionally substituted alkylene chain; Z is (1) an amino group substituted with an optionally substituted hydrocarbon group, (2) an optionally substituted imino group or (3) an optionally substituted nitrogen-containing heterocyclic group; provided that when X is a direct bond and Z is an optionally substituted 6-membered nitrogen-containing aromatic heterocyclic group, Y is an optionally substituted divalent hydrocarbon group or an optionally substituted divalent unsaturated heterocyclic group; or a salt thereof.

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Reference£º
Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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A noncentrosymmetric coordination polymer based on the benzophenone-3,3?-disulfonyl-4,4?-dicarboxylate ligand exhibiting second-harmonic-generation responses

A 3D coordination polymer [CdK6(mu2-H2O)2(BODSDC)2(H2O)]n (1) based on the novel benzophenone-3,3?-disulfonyl-4,4?-dicarboxylate (BODSDC4?) ligand was synthesized and structurally characterized. The carboxylate and sulfonate groups of the organic ligands as well as the bridging water molecules connect the Cd2+ and K+ ions to produce a 2D layer, which is linked by the benzophenone moieties to give a 3D pillared framework. Compound 1 crystallizes in an acentric space group of Cc and has a large second-harmonic-generation (SHG) response of 1.3 times that of potassium dihydrogen phosphate (KDP) in the particle size of 25?210 mum. Further SHG measurements revealed that the material is type-I phase-matchable. The observed SHG efficiency is associated with the unsymmetrical geometry of the organic ligand and the distorted coordination polyhedrons of metal centers.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Process for preparing 4-(4′-carboxyphenyl)pyridine

The invention relates to a process for preparing 4-(4?-carboxyphenyl)pyridine, which comprises oxidizing a 4-phenyl-N-acyldihydropyridine of the formula (II) 1where R1 is a bulky alkyl, alkylaryl, arylalkyl or alkoxy group and R2 is a straight-chain or branched, substituted or unsubstituted alkyl radical having from 1 to 8 carbon atoms, by means of an oxidizing agent selected from the group consisting of permanganates, nitric acid, Cr(VI) compounds, oxygen and air to give the compound of the formula (I) 2where M is a cation.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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Two series of sandwich frameworks based on two different kinds of nanosized lanthanide(III) and copper(I) wheel cluster units

Two series of sandwich frameworks, [La6(mu3-OH) 2(ox)3L12Cu11(mu3-X) 6(mu2-X)3]¡Á8 H2O (X=Br/Cl, FJ-21 a/b; L=4-pyridin-4-yl-benzonate; ox=oxalate) and [Ln4(OAc) 3(H2O)4L9][Cu(mu3-I)] @Cu10(mu3-I)(mu4-I)6(mu 5-I)3]¡Á7H2O (Ln=Pr/Nd/ Sm/Eu, FJ-22 a/b/c/d; OAc=acetate) have been hydrothermally prepared. These sandwich frameworks are assembled by two different kinds of nanosized lanthanide(III) and copper(I) wheel cluster units, La18 and 3Cu@Cu24 in FJ-21, Ln24 and Cu2@Cu24 in FJ-22. The synergistic coordination between organic ligands, L and oxalate/acetate, leads to the formation of La18 and Ln24 wheels, while the synergistic coordination between organic L and inorganic Br/I ligands results in 3Cu@Cu24 and Cu2@Cu24 wheels for FJ-21 and FJ-22, respectively. Thus, two types of synergistic coordination between two different organic ligands, as well as inorganic and organic ligands are simultaneously observed in FJ-21 and FJ-22. Synergistic coordination: Two types of synergistic coordination between organic 4-pyridin-4-yl-benzonate and oxalate/acetate ligands, as well as organic 4-pyridin-4-yl-benzonate and inorganic Br/I ligands were simultaneously observed in two series of sandwich frameworks based on linkages of two distinct layered networks of nanosized LnIII and CuI wheels, La18/3Cu@Cu24 in FJ-21 and Ln24/Cu2@Cu24 in FJ-22, by 4-pyridin-4-yl-benzoate ligands (see figure).

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Tetrahydroisoquinoline – Wikipedia,
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HETEROCYCLIC SULFONAMIDE DERIVATIVES AS INHIBITORS OF FACTOR XA

The invention relates to compounds of formula (I), wherein R 1 , R 2 and R 3 are independently selected from carbon and nitrogen, and where at least one of R 1 , R 2 and R 3 is nitrogen; A is a single bond or a double bond; n is 0, 1, 2 or 3; each R 4 is independently selected from hydrogen, C 1-3 alkyl, hydroxy, oxo and thioxo; R 5 is hydrogen or oxo; m is 0, 1, 2 or 3; each R 6 is independently selected from hydrogen, C 1-5 alkyl, oxo, carboxy, cyano, tetrazolyl, hydroxy C 1-5 alkyl, carboxy C 1-5 alkyl, C 1-5 alkylcarboxy, C 1-5 alkoxyoxo C 1-5 alkyl, carbamoyl, C 1-5 alkylcarbamoyl, di(C 1-5 alkyl) carbamoyl, -CONR 80 (CH 2 ) x S(O) p R 9 , -CONH(CH 2 ) q NR 10 R 11 , -C 1-5 alkyl-Y 1 , -COOCHR 17 R 18 and -CON R 17 R 18 ; R 7 is carbon or nitrogen; p1 is 0, 1 or 2; each R 8 is independently selected from hydrogen and halogen; or a pharmaceutically acceptable salt thereof, said compounds possess antithrombotic and anticoagulant properties and are accordingly useful in methods of treatment of humans or animals. The invention also relates to processes for the preparation of the compounds, to their use, to pharmaceutical compositions comprising them, to their use in the manufacture of medicaments for use in the production of an antithrombotic or anticoagulant effect, and to combinations comprising them

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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A new class of thermo- and solvatochromic metal-organic frameworks based on 4-(pyridin-4-yl)benzoic acid

Using 4-(pyridin-4-yl)benzoic acid, 44pba (1) as a ligand, two new metal-coordination networks [Co4(44pba)8] n¡¤[(DMF)3¡¤(EtOH) 0.25¡¤(H2O)4]n (2) and [Ni4(44pba)8]n¡¤[(DMF) 3.5¡¤(EtOH)¡¤(H2O)1.5]n (3) were synthesized by solvothermal methods and structurally characterized. Compounds 2 and 3 are isostructural but differ in their solvent content. Each is a 2D-network which forms a spiral parallel to [001], giving rise to three distinct large channels, accounting for some 47% of the unit cell volume. Both 2 and 3 display water-induced phase transformations with chromotropism, which has been confirmed by TGA and XRPD analysis. Solvatochromism in 2 is also evident with crystals exhibiting a range of colours depending on the solvent included. This phenomenon has been characterized using TGA, XRPD and UV-vis spectrophotometry. The Royal Society of Chemistry 2012.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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OTAMIXABAN FOR USE IN THE TREATMENT OF NON-ST ELEVATION ACUTE CORONARY SYNDROME IN PATIENTS PLANNED TO UNDERGO CORONARY ARTERY BYPASS GRAFTING

The invention relates to otamixaban or a pharmaceutically acceptable salt thereof for use in the treatment of non-ST elevation acute coronary syndrome in patients planned to undergo coronary artery bypass grafting.

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Identification of Selective Dual ROCK1 and ROCK2 Inhibitors Using Structure-Based Drug Design

A HTS campaign identified compound 1, an excellent hit-like molecule to initiate medicinal chemistry efforts to optimize a dual ROCK1 and ROCK2 inhibitor. Substitution (2-Cl, 2-NH2, 2-F, 3-F) of the pyridine hinge binding motif or replacement with pyrimidine afforded compounds with a clean CYP inhibition profile. Cocrystal structures of an early lead compound were obtained in PKA, ROCK1, and ROCK2. This provided critical structural information for medicinal chemistry to drive compound design. The structural data indicated the preferred configuration at the central benzylic carbon would be (R), and application of this information to compound design resulted in compound 16. This compound was shown to be a potent and selective dual ROCK inhibitor in both enzyme and cell assays and efficacious in the retinal nerve fiber layer model after oral dosing. This tool compound has been made available through the AbbVie Compound Toolbox. Finally, the cocrystal structures also identified that aspartic acid residues 176 and 218 in ROCK2, which are glutamic acids in PKA, could be targeted as residues to drive both potency and kinome selectivity. Introduction of a piperidin-3-ylmethanamine group to the compound series resulted in compound 58, a potent and selective dual ROCK inhibitor with excellent predicted drug-like properties.

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A porous 4-fold-interpenetrated chiral framework exhibiting vapochromism, single-crystal-to-single-crystal solvent exchange, gas sorption, and a poisoning effect

The synthesis and characterization of a 4-fold-interpenetrated pseudodiamond metal-organic framework (MOF), CoII(pybz) 2¡¤2DMF [pybz = 4-(4-pyridyl)benzoate], are reported. N,N-Dimethylformamide (DMF) of the channels can be removed to give the porous framework, and it can also be exchanged for methanol, ethanol, benzene, and cyclohexane. It is a rare example of a stable MOF based on a single octahedral building unit. The single-crystal structures of CoII(pybz) 2¡¤2DMF, CoII(pybz)2, Co II(pybz)2¡¤4MeOH, and CoII(pybz) 2¡¤2.5EtOH have been successfully determined. In all of them, the framework is marginally modified and contains a highly distorted and strained octahedral node of cobalt with two pyridine nitrogen atoms and two chelate carboxylate groups. In air, the crystals of CoII(pybz) 2¡¤2DMF readily change color from claret red to light pink. Thermogravimetric analysis and Raman spectroscopy indicate a change in coordination, where the carboxylate becomes monodentate and an additional two water molecules are coordinated to each cobalt atom. In a dry solvent, this transformation does not take place. Tests show that CoII(pybz) 2 may be a more efficient drying agent than silica gel and anhydrous CuSO4. The desolvated CoII(pybz)2 can absorb several gases such as CO2, N2, H2, and CH 4 and also vapors of methanol, ethanol, benzene, and cyclohexane. If CoII(pybz)2 is exposed to air and followed by reactivation, its sorption capacity is considerably reduced, which we associate with a poisoning effect. Because of the long distance between the cobalt atoms in the structure, the magnetic properties are those of a paramagnet.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem

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NEW AMINOACID COMPOUNDS FOR TREATING TUMOURS AND AUTOIMMUNE DISEASES

A compound of formula (I) or a pharmaceutically acceptable salt or solvate thereof, wherein: – R’ is H or F or trifluoromethyl; – R” is OH or O-alkyl; – R”’ is H or F or trifluoromethyl or phenyl or pyridyl; – R”” is methylene or acylsulfanyl or phenacylsulfanyl or aryloylsulfanyl or thien-2-ylsulfanyl, thiazol-2-ylsulfanyl; – n is 0 or 1, as well as pharmaceutical composition containing at least of such compounds for treating neoplasms, including tumours and carcinomas, and autoimmune diseases, including rheumatoid arthritis.

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Tetrahydroisoquinoline – Wikipedia,
1,2,3,4-Tetrahydroisoquinoline | C9H11N – PubChem