Derivatives of isoxazolina C6 and C9 - replaced; their use for the manufacture of a Medicament, and Pharmaceutical composition

摘要

1. This list refers to the substituted tricyclic isoxazolina derivatives, especially dihydrobenpiranisoxazolina and dihydro quinoolinosoxazolina derivatives, In the formula (1), there is at least one phenyl part of the tricyclic ring part at the positions of C6 and C9, and there is one radical three ring part of the selected positions, namely, dikhoronaftalenosoxazolina and dihydrobenzotioponios xazolina. 1. Preparation of drugs by using the compound; including drug synthesis of the compound, and use as drugs, especially for the treatment of depression, anxiety, motor disorders, psychosis,Parkinson's disease and weight disorders. At present, the compounds show surprisingly that they have the activity of inhibiting the reabsorption of serotonin (5-HT) in combination with the additional antagonistic activity of ALF receptor.A2 adrenaline, which shows strong antidepressant activity rather than sedatives. It is also mentioned in the present paper that isoxazolina derivatives are recombined with one or more other compounds selected from antidepressants.Antianxiety, antipsychotics and anti Parkinson's drugs to improve effectiveness and / or the beginning of action.1. A.1. Acid additive salt or pharmaceutically acceptable acid group selected from hydrogen, tar, AR, tar, tar and tar group, its stereoisomerization isomer form and positive oxidation form: X is CH2, n-r7, s or O; Ammonium carbamate and monkey and di - (TAR) carbamate; R1, R2, R14, R15 are independently selected from the hydrogen group; halogenation; a radical substance selected from the hydrogen group, so2h, so2ch3, asphalt, hydroxyoxyformic acid, carbamate, tetrahydrofuran group, Carbohydrate Xipyridinylcarbonyloxy, alkylcarbonyloxyalkyloxy, alkyloxyalkylcarbonyloxyalkyloxy, alkyloxycarbonyloxy, alkenyloxy, alkenylcarbonyloxy, mono- or di (alkyl) aminoalkyloxy, mono- or di (alkyl) aminocarbonyloxyalkyloxy; a radical selected from the group of cyano, CN-OH, CN-oxyalkyl, alkyl, alkyloxyalkyl, alkyloxyalkyloxyalkyl, alquiloxialquiloxialquiloxialquilo, alkylcarbonylalkyl, alkylcarbonyloxyalkyl, alkyloxycarbonylalkyl, Ar-alkyl, Ar-carbonylalkyl, Ar-oxyalkyl, mono- or di (alkyl) aminoalkyl , mono- or di (alkylcarbonyl) aminoalkyl, mono- or di (alkyl) aminocarbonyl-,alkyl, Het-alkyl, formyl, alkylcarbonyl, alkylcarbonyl, alkyloxyalkylcarbonyl, mono- or di (alkyl) aminocarbonyl, Ar-carbonyl and Ar-oxycarbonyl; -N-R10R11 where R10 and R11 each, independently of the other, are selected from the group consisting of hydrogen, alkyl, Ar, pyridinyl, Ar-alkyl, pyrrolidinyl alkyl, piperidinyl alkyl, homopiperidinyl alkyl, piperazinyl alkyl, morpholinyl alkyl, mono- or di (alkyl ) aminocarbonyl, alkylcarbonyl, alkenylcarbonyl, Ar-carbonyl, pyridinylcarbonyl, alkyloxycarbonyl, mono- or di (alkyl) aminocarbonyl, mono-di (Ar) aminocarbonyl, mono- or di (alkyloxycarbonylalkyl) aminocarbonyl, pyrrolidinylcarbonyl,1. Carbamate, polyaminobenzamide, n-phenylpyridyl methyl ester, alkylhydrazide, and AR sulfonilo;Or R10 and R11 can be used together to form a monovalent radical selected from the formula residue group (2),Among them, R12 is selected from hydrogen, asphalt, AR, AR asphalt, AR alquenilo, asphalt, tar, tar, carbamate or di - (TAR) aminobenzene; each R13 is,Independent of one of another group of substances composed of asphalt, oxo, AR, AR asphalt, AR acquilo, AR alquenilo and hydrocarbon poisoning; q is an integer of 0-6; aspha AR and het; provided that at least one R14 and R15 are not hydrogen. AR is phenyl or nafilo, which can be replaced by one or more halogens, cyanogens, oxo, hydroxy, hydrocarbyl, hydrocarbyl, thyroid, hydrocarbyl or amino groups; het is a heterocyclic radical substance selected from het1, het2 and het3 groups; hett1 is a heterocyclic monocyclic aromatic radical substance selected from pirrolidini, dioxylo and imidazolidini groups, Pyridienediene, morphine dienediene, dienedieneHet2 is a semi aromatic, single cycle and anti cyclical radical substance of 2H pirrolilo, pyridinol, pyridine xylene and pyridine diene; hett3 is a single cycle and anti cycle and anti cycle radical substance selected from pyridinol, pyridine diene, pyridine diene, pyridine diene, furan, geranyl ester and oxazolilo, 1. Thiazolyl, isothiazolyl, pyridylene, pyridylene, pyridylene, pyridylene, and trizinc; or two cycloaromatics selected from quinoolinil, quinoxalilo, indolilo, benimidazolo, benzoxazollo, benisoxazollo, benzotiazolo, benzofuranilo and benzotianilo;In this case, each het radical may be replaced by carbon or heteroatom, halogenated, hydrogen Xi, asphalt, tar, tar, AR, asphalt, thyroid, tar or pyridine; a and B are asymmetric centers; (CH2) (m) is a straight Carbide chain composed of protons m, M is an integer 1 to 4 carbon atom; PIR is a radical agreement to replace any one of the alternative groups with n-radical R8, where each R8 is,Independently selected from the groups of hydrogen Xi, amino group, nitro group, cyanogen group, halogen group and tar group; n is the integer 0 to 5; R9 is selected from the groups of hydrogen, tar group and thyroid group; R3 represents a selective aromatic ring system with the same or different ring, and is replaced with some carbide chains. O complete hydrogenation can selectively replace 1 to 6 atoms in length to combine the ring system with the giant reactor, and may contain one or more heteroatoms selected from the O, N and s groups;1. Tar refers to a saturated straight-line or separator like hydrocarbon base composed of C1-6 or circulating C3-6 saturated hydrogen carbide filter, which can be optionally replaced by one or more halogenated, oxo, hydroxi, thyroid or amino bodies, and represents an unsaturated straight-line or separator like carbide filter. One or more radicals in the group of halogenated, cyanogen, oxo, hydroxy, thyroid or aminobenzene can be selected to replace the double bond.