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US 7,211,589 B2Granted
Atisane compounds and use thereof
AssigneeEisai R&D Management Co., Ltd.
InventorsAkinori Akaike, Hachiro Sugimoto, Yukio Nishizawa, Masahiro Yonaga, Naoki Asakawa, Naoki Asai, Nariyasu Mano, Taro Terauchi, Takashi Doko
Life of this patent
Estimating the term…
Abstract
The present invention provides a novel compound exhibiting an excellent suppressing effect to cell injury caused by radicals and neurotoxicity induced by excitatory nuerotransmitters such as glutamate. Specifically, it provides a compound represented by the following formula, a salt thereof or a hydrate of them. Wherein Z represents a bivalent organic group and the like of from 2 to 3 carbon atom(s) which may have a substituent; and R3 represents a carboxyl group and the like.
Claims22
A compound represented by the following formula, or a salt thereof or a hydrate thereof:
- wherein Z is a group represented by the formula:
- wherein Q1 is
- wherein A1 represents an optionally substituted C1-6 alkylene group or a single bond;
- X1 represents a halogen atom or a cyano group;
- X2 represents the formula —S(O)m—, an oxygen atom, a carbonyl group or a single bond, wherein m of —S(O)m— is an integer of 0, 1 or 2;
- R4a represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C1-6 alkoxy group or a hydroxyl group;
- and
- R4b and R4c are independent of each other and each represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C2-7 acyl group or an optionally substituted C1-6 alkylsulfonyl group;
- Q2a represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C1-6 alkoxy group, a hydroxyl group or a group represented by the formula —NR6aR6b, wherein R6a and R6b are independent of each other and each represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C2-7 acyl group or an optionally substituted C1-6 alkylsulfonyl group:
- R3a represents a carbonyl group, a methylene group or a single bond;
- and
- R3b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C1-6 alkoxy group, a hydroxyl group, a cyano group or a group represented by the formula —NR5aR5b,
- wherein R5a and R5b are independent of each other and each represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C2-7 acyl group or an optionally substituted C1-6 alkylsulfonyl group, provided that the following cases (1) to (3) are excluded:
- (1) Z represents a 1,2-dicarboxyethane-1,2-yl group or a 1,2-dimethoxycarbonylethane-1,2-yl group, and the formula —R3a–R3b represents a hydroxymethyl group or an acetoxymethyl group;
- (2) Z represents a 1-i-propylethane-1,2-yl group and the formula —R3a–R3b represents a hydrogen atom;
- and
- (3) the formula —R3a–R3b represents a methyl group, and Z represents the formula:
- wherein R11 represents a hydrogen atom or a methyl group, and R12 represents a hydroxyl group, a methyl group or a tetrahydropyran-2H-pyran-2-yl-oxy group.
15 more elements
A compound represented by the following formula, or a salt thereof or a hydrate thereof:
- wherein Z represents a bivalent organic group of from 2 to 3 carbon atoms, provided that Z may have one or two group(s) selected from the group consisting of those represented by the following formula:
- wherein A1 represents an optionally substituted C1-6 alkylene group or a single bond;
- X1 represents a halogen atom or a cyano group;
- X2 represents the formula —S(O)m—, an oxygen atom a carbonyl group or a single bond, wherein m of —S(O)m— is an integer of 0, 1 or 2;
- R4a represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C1-6 alkoxy group or a hydroxyl group;
- and
- R4b and R4c are independent of each other and each represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C2-7 acyl group or an optionally substituted C1-6 alkylsulfonyl group;
- wherein in the case where Z is a 1,2-ethylene group not having a substituent or a 1,2-vinylene group not having a substituent is excluded;
- R3a represents a carbonyl group, a methylene group or a single bond;
- and
- wherein R3b is a hydroxyl group.
8 more elements
A compound represented by the following formula, or a salt thereof or a hydrate thereof:
- wherein Z is a group represented by the formula:
- wherein Q1 is a group represented by the formula -A1-S(O)m—R4a, wherein A1 represents an optionally substituted C1-6 alkylene group or a single bond, m is an integer of 0, 1 or 2, and R4a represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C1-6 alkoxy group or a hydroxyl group;
- wherein Q2 represents a group represented by the formula:
- wherein A1 represents an optionally substituted C1-6 alkylene group or a single bond;
- X1 represents a halogen atom or a cyano group;
- X2 represents the formula —S(O)m—, an oxygen atom, a carbonyl group or a single bond, wherein m of —S(O)m— is an integer of 0, 1 or 2;
- R4a represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C1-6 alkoxy group or a hydroxyl group;
- and
- R4b and R4c are independent of each other and each represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C2-7 acyl group or an optionally substituted C1-6 alkylsulfonyl group;
- wherein in the case where Z is a 1,2-ethylene group not having a substituent or a 1,2-vinylene group not having a substituent is excluded;
- R3a represents a carbonyl group, a methylene group or a single bond;
- and
- R3b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C1-6 alkoxy group, a hydroxyl group, a cyano group or a group represented by the formula —NR5aR5b,
- wherein R5a and R5b are independent of each other and each represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C2-7 acyl group or an optionally substituted C1-6 alkylsulfonyl group,
- provided that the following cases (1) to (3) are excluded:
- (1) Z represents a 1,2-dicarboxyethane-1,2-yl group or a 1,2-dimethoxycarbonylethane-1,2-yl group, and the formula —R3a–R3b represents a hydroxymethyl group or an acetoxymethyl group;
- (2) Z represents a 1-i-propylethane-1,2-yl group and the formula —R3a–R3b represents a hydrogen atom;
- and
- (3) the formula —R3a–R3b represents a methyl group, and Z represents the formula:
- wherein R11 represents a hydrogen atom or a methyl group, and R12 represents a hydroxyl group, a methyl group or a tetrahydropyran-2H-pyran-2-yl-oxy group.
17 more elements
A compound represented by the following formula, or a salt thereof or a hydrate thereof:
- wherein Z represents a bivalent organic group of from 2 to 3 carbon atoms, provided that Z may have one or two group(s) selected from the group consisting of those represented by the following formula:
- wherein A1 represents an optionally substituted C1-6 alkylene group or a single bond;
- X1 represents a halogen atom or a cyano group;
- X2 represents the formula —S(O)m—, wherein m is 1;
- R4a represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C1-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C1-6 alkoxy group or a hydroxyl group;
- and
- R4b and R4c are independent of each other and each represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C2-7 acyl group or an optionally substituted C1-6 alkylsulfonyl group;
- wherein in the case where Z is a 1,2-ethylene group not having a substituent or a 1,2-vinylene group not having a substituent is excluded;
- R3a represents a carbonyl group, a methylene group or a single bond;
- and
- R3b represents a hydrogen atom, a halogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C1-6 alkoxy group, a hydroxyl group, a cyano group or a group represented by the formula —NR5aR5b,
- wherein R5a and R5b are independent of each other and each represents a hydrogen atom, an optionally substituted C1-6 alkyl group, an optionally substituted C2-6 alkenyl group, an optionally substituted C2-6 alkynyl group, an optionally substituted C6-14 aromatic hydrocarbon cyclic group, an optionally substituted from 5- to 14-membered aromatic heterocyclic group, an optionally substituted C2-7 acyl group or an optionally substituted C1-6 alkylsulfonyl group,
- provided that the following cases (1) to (3) are excluded:
- (1) Z represents a 1,2-dicarboxyethane-1,2-yl group or a 1,2-dimethoxycarbonylethane-1,2-yl group, and the formula —R3a–R3b represents a hydroxymethyl group or an acetoxymethyl group;
- (2) Z represents a 1-i-propylethane-1,2-yl group and the formula —R3a–R3b represents a hydrogen atom;
- and
- (3) the formula —R3a–R3b represents a methyl group, and Z represents the formula:
- wherein R11 represents a hydrogen atom or a methyl group, and R12 represents a hydroxyl group, a methyl group or a tetrahydropyran-2H-pyran-2-yl-oxy group.
15 more elements
Dependencies are inferred from the claim text.