Indolin-2-one Derivatives, their use and Process for their preparation, Pharmaceutical composition containing the Derivative, that is, a product containing Said derivative and a vasopressin receptor antagonist

摘要

Indolin-2-ona derivative, in the form of pure corresponding isomer or formula isomer mixture (1), wherein R0 represents a group selected from formula (2), in which Z1 represents the atom of chlorine, bromine, iodine or fluorine, C1-4 tar, alcox C1-4 or trifluoro isomer, Z2 represents the atom of hydrogen, chlorine, bromine, iodine or fluorine, C1-4, cycloquilo c3-5, alcoxi C1-4, cyclooxy c3-5 or polyfluoropropylsulfonyl C1-4; R5 represents T1W, where T1 represents - (CH2) m, m equals 0 or 1; W represents hydrogen, hydrofluorocarbon (or carboxyl),Carbon chloride C1-4, 1, 3-dioxolan-2-ilo, 1, 3-dioxan-2-ilo, or W represents a separate R6 and R7 group,A hydrogen atom, a C1-4 tar, a C1-4 tar, or a phenyl sulfonyl, in which the phenyl can be a single, a binary, or a trifluoride Z5; or R6 and R7 are made up of nitrogen atoms with which the unidentified lini is eventually replaced by asphalt or oxo, R6 and R7 are made up of nitrogen atoms, combined with nitro compounds, and finally replaced by Z3 to 4; or R6 and R7 are made up of nitrogen atoms, combined with pyridine or pyridine, and finally replaced by Z4.Or W stands for a group-n8cor9, wherein R8 stands for hydrogen atom or C1-4 and R9 tar, stands for hydrogen, C1-4 tar, biphenyl, pyridine and phenyl, and such phenyl can be monomer, class II or class III Z5; or R9 stands for a group-n10r11, wherein R10 and R11 are independent representatives,Hydrogen atom or C1-4 tar or R10 and R11 are composed of nitrogen atom, with pyridine, pyridine or morphine alcohol connected, and finally replaced by C1-4 tar, or R9 represents pyridine-2-ilo or 3-ilo, pyridine-2-ilo, 3-ilo or 4-ilo, These pyridines and pyridinedienes are eventually replaced by z7; or R9 represents a population - t2-r12 or - t2-cor12, where T2 represents - (CH2) n -.N may equal 1, 2, 3, 4, and R12, representing alcox C1-4 or - n10r11, R10, and R11, as described above; or W represents a set of - conr13r14, where R13 represents a hydrogen atom, C1-4 tar, c3-7 cyclopentadiene, C1-4 tar, and R14 represents a hydrogen atom, C1-4 tar, Phenyl is finally replaced by Z5, t4-r15, wherein T4 stands for - (CH2) Q, q is equal to 1, 2, 3 or 4, R15 stands for hydroxyl group, alcoxi C1-4, alcoxicarbon C1-4, alcoxicarbolinilamino C1-4, and phenyl is finally monkey,Z5, a pyridan-2-ilo, 3-ilo or 4-ilo, n16r17, wherein R16 and R17 respectively represent them,The hydrogen atom, or C1-4 tar, or R16 and R17 are composed of nitrogen atoms, which may be connected with mono state mofflin, or mofflin dissolved in C1-4 tar, or R16 and R17 are composed of nitrogen atoms, plus position 4, or R16 and R17 finally replaced by Z3 substitutes. When q = 1, R15 is different from hydroxy group, alcoxi C1-4, alcoxi carbonilamino C1-4 and - n16r17.Or R13 and R14 are made up of nitrogen atoms, including a group that may be monkeys or sulfur dioxide, or a group of C1-4 tar, and eventually replaced by a Z3 substitute to level 4, or R13 and R14 are made up of nitrogen atoms and combined with azetidini, pirrolidini or piperidiilo, Hexahydroazerbaijanis, such pyridyl, pyridyl and hexahydroazerbaijanis may be converted into monomers or desulfurized by Z8; or W represents an or18 group, wherein R18 represents hydrogen atom, C1-4 tar, alcox C1-4 c1-3-r19, wherein T3 represents - (CH2) P -,P may be equal to the components of 2, 3 and R19, which are hydroxy, triphenylmethyl ether nr20r21, wherein R20 represents a hydrogen atom or C1-4 and R21 tar, represents a hydrogen atom, C1-4 tar, tetrahydrofuran or tetrahydropyridine alcohol, or R20 and R21 are composed of nitrogen atoms attached to them, Morphine or sulfur dioxide, which may be made from C1-4 tar, pyridinium and R21, which may be replaced by Z3 or R20 and R21 substitutes, are composed of nitrogen atoms. They are linked with nitrogen atoms, and pyridinium or piperidinilo are finally replaced by Z5; Z3 is tar,pyridyl or C1-4 phenyl, C1-4 alkylcarbonyl, C1-4 alkoxycarbonyl; Z4 represents an oxo, a fluorine atom, hydroxyl, C1-4 alkyl, benzyl, amino, C1-4 alkylamino, C1-4 alkylamino, C1-4 alkoxy, C1-4 alkoxycarbonyl, C1-4 alkoxycarbonylamino; Z5 represents a chlorine, bromine, iodine or fluorine atom, hydroxy C1-4 alkyl, or C1-4 alkoxy; Z7 represents a fluorine, hydroxyl, hydroxy C1-4 alkyl, C1-4 alkyl, C1-4 alkoxy, C1-4 alkylcarbonyl atom; Z8 represents a fluorine atom, hydroxy C1-4 alkyl, C3-6 cycloalkyl, benzyl, amino, C1-4 alkylamino, C1-4 dialkylamino, C1-4 alkoxycarbonyl, C1-4 alkoxycarbonylamino, C3-6 cycloalkoxy, hydroxycarbonyl,C1-4 or alcoxi C1-4 C1-4 hydrocarbon, alcoxi C1-4, alcoxi C1-4, conr23r24, wherein R23 and R24 are independent,Hydrogen atom, C1-4 tar, monomer or perfluorocarbon C1-4 or R23 and R24 are composed of nitrogen atoms and connected with them, such as pyridine or pyridine, which is finally replaced by Z3 or difluoromethane; O R0 represents a group selected from formula (3) Z6, representing chlorine atom or alcoxi of C1-4 tar or C1-4; R1 represents C1-4 tar, which may have two or three links, namely alcoxicarbon of C1-4; Benzodiazepine or t1-r22 group, where T1 is the above definition, R22 represents a hydroxyl group or alcoxi C1-4 group; R2 and R4 represent them respectively,Hydrogen, chlorine or fluorine atom, C1-4 tar or alcox C1-4 or alcox C1-4; R3 represents chlorine or fluorine, hydroxyl, C1-4 tar, alcoxi C1-4, carbamate C1-4, C1-4 tar, nitrate, cyanogen, trifluoroethane, carbamate, c13-6, rental C1-4, c1-4-1 carat, trithyroid carat, C14A-is anion; pirrolidin-1-ilo, piperizin-1-ilo, morfolin-4-ilo or hexahydroazepin-1-ilo; x E represents them respectively,An atom of hydrogen, chlorine, bromine, iodine or fluorine, or C1-4 or trifluoroiodine chloride, and salts, solutions, and hydrates acceptable to its drug. Formula compound (1) is similar to oxytocin receptor. Its use, preparation procedures, pharmaceutical ingredients containing the substance, and drugs composed of formula compound (1),And a product containing formula compound (1),There is also a product that contains a formula compound (1) oxytocin receptor for keratin and an angiogenin receptor for keratin.