Patent ES-8504813-A1 (ES)
Title: Benzoxazin-2-one derivs.
IPC: C07D498/00
Filed: 1983-10-25
Abstract: Benzoxazine-2-one derivs. of formula (I) are new (where A is S, SO, SO2, RN:S- or gp. (a), R is H or an acyl gp. derived from an organic carboxylic acid, an organic or inorganic sulphonic acid or a carbonic acid deriv.; D is opt. branched 2-6C alkylene. R1 is 1-3C alkyl (opt. substd. by Ph), Ph (these Ph gps. opt. mono-substd. by 1-4C alkyl, halogen, 1-3C alkoxy, OH, cyclohexyl, Ph or 1-3C alkanoylamino), 4-8C alkyl, 3-7C cycloalkyl, Ph (di- or tri-substd. by 1-4C alkyl, 1-3C alkoxy and/or halogen) disubstd. hydroxy- or aminophenyl or pyridyl. R2 and R3 are each H, Ph, 1-6C alkyl, or 3-7C cycloalkyl; R4 is H or 1-3C alkyl). - (I) have pharmacological properties, esp. antithrombotic properties. (I) increase the synthesis of aggregation inhibitor Prostaglandin I2 (Prostacyclin). (I) also inhibit tumour metastasis. Suitable doses are 0.3-4 mg/kg. 2-4 times daily.  (0/0) EPAB- EP--93922 B Benzoxazin-2-ones of general formula (I) wherein A represents a sulphur atom, an SO-, SO2-, R-N=S- or R-N=SO-group, wherein R represents a hydrogen atom, a straight-chained alkanoyl group with 1 to 9 carbon atoms, a pivaloyl group, a benzoyl group optionally substituted by a fluorine, chlorine or bromine atom or by a methyl, ethyl, isopropyl, tert.buty or acetoxy group, a benzoyl group substituted by two fluorine atoms, two chlorine atoms, two or three methyl groups, a phenylsulphonyl group optionally substituted by a methyl group or by a fluorine, chlorine or bromine atom, a naphthoyl, thenoyl, pyridinoyl, hydroxysulphonyl, methanesulphonyl, ethanolsulphonyl, pentamethylphenylsulphonyl, methoxycarbonyl, ethoxycarbonyl, n-propoxy-carbonyl, isopropoxycarbonyl, benzyloxycarbonyl, aminocarbonyl, methylaminocarbonyl or dimethylaminocarbonyl group, D represents a straight-chained or branched alkylene group with 2 to 6 carbon atoms, R1 represents an alkyl group with 1 to 3 carbon atoms optionally substituted by a phenyl group or a phenyl group, whilst the above-mentioned phenyl nuclei may each be substituted by an alkyl group with 1 to 4 carbon atoms, a halogen atom, an alkoxy group with 1 to 4 carbon atoms, a hydroxy, cyclohexyl or phenyl group, an amino group or an alkanoylamino group with 1 to 3 carbon atoms; an alkyl group with 4 to 8 carbon atoms, a cycloalkyl group with 3 to 7 carbon atoms, a phenyl group di- or trisubstituted, or a  hydroxyphenyl or aminophenyl group mono- or disubstituted, by alkyl groups with 1 to 4 carbon atoms, alkoxy groups with 1 to 3 carbon atoms and/or halogen atoms, whilst the substituents of the phenyl nucleus may be identical or different, a pyridyl or pyrimidinyl group optionally substituted by one or two methyl groups, or a pyridyl-N-oxide, ethyl-pyridyl, ethyl-pyrimidinyl, propyl-pyrimidinyl, diethyl-pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolyl, triazolyl, indolyl, indazolyl, quinolyl, isoquinolyl quinazolinyl, benzim - EP--93922 B Benzoxazin-2-ones of general formula (I) wherein A represents a sulphur atom, an SO-, SO2-, R-N =S- or R-N =SO-group, wherein R represents a hydrogen atom, a straight-chained alkanoyl group with 1 to 9 carbon atoms, a pivaloyl group, a benzoyl group optionally substituted by a fluorine, chlorine or bromine atom or by a methyl, ethyl, isopropyl, tert.buty or acetoxy group, a benzoyl group substituted by two fluorine atoms, two chlorine atoms, two or three methyl groups, a phenylsulphonyl group optionally substituted by a methyl group or by a fluorine, chlorine or bromine atom, a naphthoyl, thenoyl, pyridinoyl, hydroxysulphonyl, methanesulphonyl, ethanolsulphonyl, pentamethylphenylsulphonyl, methoxycarbonyl, ethoxycarbonyl, n-propoxy-carbonyl, isopropoxycarbonyl, benzyloxycarbonyl, aminocarbonyl, methylaminocarbonyl or dimethylaminocarbonyl group, D represents a straight-chained or branched alkylene group with 2 to 6 carbon atoms, R1 represents an alkyl group with 1 to 3 carbon atoms optionally substituted by a phenyl group or a phenyl group, whilst the above-mentioned phenyl nuclei may each be substituted by an alkyl group with 1 to 4 carbon atoms, a halogen atom, an alkoxy group with 1 to 4 carbon atoms, a hydroxy, cyclohexyl or phenyl group, an amino group or an alkanoylamino group with 1 to 3 carbon atoms; an alkyl group with 4 to 8 carbon atoms, a cycloalkyl group with 3 to 7 carbon atoms, a phenyl group di- or trisubstituted, or a hydroxyphenyl or aminophenyl group mono- or disubstituted, by alkyl groups with 1 to 4 carbon atoms, alkoxy groups with 1 to 3 carbon atoms and/or halogen atoms, whilst the substituents of the phenyl nucleus may be identical or different, a pyridyl or pyrimidinyl group optionally substituted by one or two methyl groups, or a pyridyl-N-oxide, ethyl-pyridyl, ethyl-pyrimidinyl, propyl-pyrimidinyl, diethyl-pyrimidinyl, pyrazinyl, pyridazinyl, pyrazolyl, imidazolyl, triazolyl, indolyl, indazolyl, quinolyl, isoquinolyl quinazolinyl, benzim GBAB- GB2119382 B Compounds of general formula (I) wherein A represents a sulphur atom or an SO, SO2, R-N=S or R-N=SO group (wherein R represents a hydrogen atom or an acyl group of an organic carboxylic acid, of an organic or inorganic sulphonic acid or of a carbonic acid derivative); D represents a straight-chained or branched alkylene group containing 2 to 6 carbon atoms; R1 represents an alkyl group containing 1 to 3 carbon atoms (optionally substituted by a phenyl group) or a phenyl group, each of the above-mentioned phenyl nuclei being optionally substituted by an alkyl group containing 1 to 4 carbon atoms, by a halogen atom, by an alkoxy group containing 1 to 3 carbon atoms, by a hydroxy, cyclohexyl, phenyl or amino group or by an alkanoylamino group containing 1 to 3 carbon atoms; an alkyl group containing 4 to 8 carbon atoms; a cycloalkyl group containing 3 to 7 carbon atoms; a phenyl group di-or tri-substituted by alkyl groups containing 1 to 4 carbon atoms, b by alkoxy groups containing 1 to 3 carbon atoms and/or by halogen atoms (wherein the substituents of the phenyl nucleus may be the same or different); a hydroxyphenyl or aminophenyl group mono-or di-substituted by alkyl groups containing 1 to 4 carbon atoms, by alkoxy groups containing 1 to 3 carbon atoms and/or by halogen atoms (wherein the substituents of the phenyl nucleus may be the same or different); a pyridyl-N-oxide group or a 5- or 6-membered aromatic ring optionally substituted by one or two alkyl groups each containing 1 to 3 carbon atoms, this aromatic ring containing 1 to 3 nitrogen atoms or 1 nitrogen atom and 1 sulphur atom, whilst a phenyl group may optionally be fused onto this aromatic ring via two adjacent carbon atoms; R2 and R3, which may be identical or different, each represents a hydrogen atom, a phenyl group, an alkyl group containing 1 to 6 carbon atoms or a cycloalkyl group containing 3 to 7 carbon atoms; R4 represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms; R5 ro - GB2119382 B Compounds of general formula (I) wherein A represents a sulphur atom or an SO, SO2, R-N =S or R-N =SO group (wherein R represents a hydrogen atom or an acyl group of an organic carboxylic acid, of an organic or inorganic sulphonic acid or of a carbonic acid derivative); D represents a straight-chained or branched alkylene group containing 2 to 6 carbon atoms; R1 represents an alkyl group containing 1 to 3 carbon atoms (optionally substituted by a phenyl group) or a phenyl group, each of the above-mentioned phenyl nuclei being optionally substituted by an alkyl group containing 1 to 4 carbon atoms, by a halogen atom, by an alkoxy group containing 1 to 3 carbon atoms, by a hydroxy, cyclohexyl, phenyl or amino group or by an alkanoylamino group containing 1 to 3 carbon atoms; an alkyl group containing 4 to 8 carbon atoms; a cycloalkyl group containing 3 to 7 carbon atoms; a phenyl group di-or tri-substituted by alkyl groups containing 1 to 4 carbon atoms, b by alkoxy groups containing 1 to 3 carbon atoms and/or by halogen atoms (wherein the substituents of the phenyl nucleus may be the same or different); a hydroxyphenyl or aminophenyl group mono-or di-substituted by alkyl groups containing 1 to 4 carbon atoms, by alkoxy groups containing 1 to 3 carbon atoms and/or by halogen atoms (wherein the substituents of the phenyl nucleus may be the same or different); a pyridyl-N-oxide group or a 5- or 6-membered aromatic ring optionally substituted by one or two alkyl groups each containing 1 to 3 carbon atoms, this aromatic ring containing 1 to 3 nitrogen atoms or 1 nitrogen atom and 1 sulphur atom, whilst a phenyl group may optionally be fused onto this aromatic ring via two adjacent carbon atoms; R2 and R3, which may be identical or different, each represents a hydrogen atom, a phenyl group, an alkyl group containing 1 to 6 carbon atoms or a cycloalkyl group containing 3 to 7 carbon atoms; R4 represents a hydrogen atom or an alkyl group containing 1 to 3 carbon atoms; R5 r USAB- US4518597 A Novel benzoxazin-2-one has formula (I), where A is S, SO, SO2, R-N=S or R-N=SO; R is H, or benzoyl or phenylsulphonyl (opt. substd. by Me), or acetyl, or propionyl; D is linear or branched (2-6C) alkylene; R2 and R3 are each opt. the same H, Ph, (1-6C) alkyl, or (3-7C) cycloalkyl; R4 is H or (1-3C) alkyl; R5 is H, halogen, NO2 or (1-3C) alkyl; and R6 is H, halogen, or (1-3C) alkyl. R1 is (1-3C) alkyl (opt. substd. by Ph) or Ph (where Ph and Ph substitit. are each opt. substd. by (1-4C) alkyl, halogen, (1-3C) alkoxy, OH, cyclohexyl, Ph, NH2, or (1-3C) alkanoylamino), or (4-8C) alkyl, (3-7C) cycloalkyl, di- or tri-substd. Ph of mono- or di-substd. hydroxyphenyl or aminophenyl (whose substits. comprise (1-4C) alkyl, (1-3C) alkoxy, and/or halogens), pyridyl-N-oxide, or 5- or 6-membered aromatic ring (opt. substd. by 1 or 2 (1-3C) alkyl) whose ring can contain 1-3N or 1N and 1S, or is a Ph ring opt. fired into aromatic ring via  2 adjacent C.