Claims
- 1. A pharmaceutical composition, comprising a pharmaceutically effective amount of a brain cell protective agent represented by formula (I') pharmacologically acceptable acid addition salt thereof: ##STR71## wherein, R.sup.1 represents an alkyl group having 1-5 carbon atoms, a cycloalkylalkyl group having 4-7 carbon atoms, a cycloalkenylalkyl group having 5-7 carbon atoms, an aryl group having 6-12 carbon atoms, an aralkyl group having 7-13 carbon atoms, an alkenyl group having 4-7 carbon atoms, an allyl group, a furan-2-ylalkyl group having 1-5 carbon atoms (wherein the number of carbon atoms is of the alkyl moiety), or a thiophen-2-ylalkyl group having 1-5 carbon atoms (wherein the number of carbon atoms is of the alkyl moiety);
- R.sup.2' represents a hydrogen atom, hydroxy group, alkanoyloxy group having 1-5 carbon atoms or alkoxy group having 1-5 carbon atoms;
- R.sup.3 represents a hydrogen atom, a hydroxy group, an alkanoyloxy group having 1-5 carbon atoms or an alkoxy group having 1-5 carbon atoms;
- A' represents --NR.sup.4' C(.dbd.O)-- or --NR.sup.4' --, wherein R.sup.4' represents a cycloalkylalkyl gropu having 4 to 15 carbon atoms (which may be substituted with at least one substituent selected from the grou consisting of an alkyl group having 1-5 carbon atoms, an aryl group havin 6-12 carbon atoms, an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, fluorine, chlorine, bromine, iodine, a nitro group, a cyano group and a trifluoromethyl group), or an aralkyl group having 7-15 carbon atoms (which may be substituted with at least one substituent selected from the group consisting of an alkyl group having 1-5 carbon atoms, an aryl group having 6-12 carbon atoms, an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, fluorine, chlorine, bromine, iodine, a nitro group, a cyano group and a trifuloromethyl group);
- B represents a valence bond, a straight chain alkylene group having 1-14 carbon atoms or a branched chain alkylene group having 3-14 carbon atoms (which may be substituted with at least one substituent selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, chlorine, bromine, iodine, an amino group, a nitro group, a cyano group, a trifluoromethyl group and a phenoxy group, and wherein from 1 to 3 methylene groups that are not adjacent may be replaced with carbonyl groups), a straight chain, acyclic, unsaturated hydrocarbon having 2-14 carbon atoms or a branched chain acyclic, unsaturated hydrocarbon having 3 to 14 carbon atoms, and having from 1 to 3 double and/or triple bonds (which may be substituted with at least one substituent selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, chlorine, bromine, iodine, an amino group, a nitro group, a cyano group, a trifluoromethyl group and a phenoxy group, and wherein from 1 to 3 methylene groups that are not adjacent may be replaced with carbonyl groups), or a straight chain, saturated hydrocarbon having 1-14 carbon atoms, a straight chain unsaturated hydrocarbon having 2-14 carbon atoms, or branched chain saturated or unsaturated hydrocarbon having 3 to 14 carbon atoms, having from 1 to 5 thioether, ether and/or amino bonds (wherein hetero atoms are not bonded directly to A, and from 1 to 3 methylene groups that are not adjacent may be replaced with carbonyl groups);
- R.sup.5 represents a hydrogen atom or an organic group having a structure as shown below: ##STR72## wherein Q is selected from the group consisting of CH, N, S or O, l is 0-5, m and n are greater than or equal to 0, and m+n is less than or equal to 5,
- and which organic group may be substituted with at least one substituent selected from the group consisting of an alkyl group having 1-5 carbon atoms, an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, chlorine, bromine, iodine, an amino group, a nitro group, a cyano group, an isothiocyanate group, a trifluoromethyl group, and a methylenedioxy group;
- wherein the formula (I') includes the (+) form, the (-) form and the (.+-.) form;
- and a pharmaceutically acceptable carrier therefor.
- 2. A morphinan derivative represented by formula (I') or pharmacologically acceptable acid addition salt thereof: ##STR73## wherein, R.sup.1 represents an alkyl group having 1-5 carbon atoms, a cycloalkylalkyl group having 4-7 carbon atoms, a cycloalkenylalkyl group having 5-7 carbon atoms, an aryl group having 6-12 carbon atoms, an aralkyl group having 7-13 carbon atoms, an alkenyl group having 4-7 carbon atoms, an allyl group, a furan-2-ylalkyl group having 1-5 carbon atoms (wherein the number of carbon atoms is of the alkyl moiety), or a thiophen-2-ylalkyl group having 1-5 carbon atoms (wherein the number of carbon atoms is of the alkyl moiety);
- R.sup.2' represents a hydrogen atom, hydroxy group, alkanoyloxy group having 1-5 carbon atoms or alkoxy group having 1-5 carbon atoms;
- R.sup.3 represents a hydrogen atom, a hydroxy group, an alkanoyloxy group having 1-5 carbon atoms or an alkoxy group having 1-5 carbon atoms;
- A' represents --NR.sup.4' C(.dbd.O)-- or --NR.sup.4' --, wherein R.sup.4' represents a cycloalkylalkyl gropu having 4 to 15 carbon atoms (which may be substituted with at least one subsdtituent selected from the grou consistin gof an alkyl group having 1-5 carbon atoms, an aryl group havin 6-12 carbon atoms, an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, fluorine, chlorine, bromine, iodine, a nitro group, a cyano group and a trifluoromethyl group), or an aralkyl group having 7-15 carbon atoms (which may be substituted with at least one substituent selected from the group consisting of an alkyl group having 1-5 carbon atoms, an aryl group having 6-12 carbon atoms, an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, fluorine, chlorine, bromine, iodine, a nitro group, a cyano group and a trifuloromethyl group);
- B represents a valence bond, a straight chain alkylene group having 1-14 carbon atoms or a branched chain alkylene group having 3-14 carbon atoms (which may be substituted with at least one substituent selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, chlorine, bromine, iodine, an amino group, a nitro group, a cyano group, a trifluoromethyl group and a phenoxy group, and wherein from 1 to 3 methylene groups that are not adjacent may be replaced with carbonyl groups), a straight chain, acyclic, unsaturated hydrocarbon having 2-14 carbon atoms or a branched chain acyclic, unsaturated hydrocarbon having 3 to 14 carbon atoms, and having from 1 to 3 double and/or triple bonds (which may be substituted with at least one substituent selected from the group consisting of an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, chlorine, bromine, iodine, an amino group, a nitro group, a cyano group, a trifluoromethyl group and a phenoxy group, and wherein from 1 to 3 methylene groups that are not adjacent may be replaced with carbonyl groups), or a straight chain, saturated hydrocarbon having 1-14 carbon atoms, a straight chain unsaturated hydrocarbon having 2-14 carbon atoms, or branched chain saturated or unsaturated hydrocarbon having 3 to 14 carbon atoms, having from 1 to 5 thioether, ether and/or amino bonds (wherein hetero atoms are not bonded directly to A, and from 1 to 3 methylene groups that are not adjacent may be replaced with carbonyl groups);
- R.sup.5 represents a hydrogen atom or an organic group having a structure as shown below: ##STR74## wherein Q is N, O or S, T is CH, N, S or O, l is 0-5, m and n are greater than or equal to 0, and m+n is less than or equal to 5,
- and which organic group may be substituted with at least one substituent selected from the group consisting of an alkyl group having 1-5 carbon atoms, an alkoxy group having 1-5 carbon atoms, an alkanoyloxy group having 1-5 carbon atoms, a hydroxy group, fluorine, chlorine, bromine, iodine, an amino group, a nitro group, a cyano group, an isothiocyanate group, a trifluoromethyl group, and a methylenedioxy group; and,
- the formula (I') includes the (+) form, the (-) form and the (.+-.) form.
Parent Case Info
This application is a divisional of application Ser. No. 08/745,041, filed on Nov. 7, 1996, now U.S. Pat. No. 5,972,953, which is a Rule 60 Divisional of Ser. No. 08/403,759 filed on Mar. 17, 1995, now abandoned, the entire contents of which are hereby incorporated by reference which claims the benefit of PCT/JP94/01186, filed on Jul. 19, 1994.
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Divisions (2)
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Number |
Date |
Country |
| Parent |
745041 |
Nov 1996 |
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| Parent |
403759 |
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Patent Grant
6147084
