Selective estrogen receptor modulator
The present invention provides a compound represented by the following formula (I); [wherein T represents a single bond, a C1-C4 alkylene group which may have a substituent and the like; formula (I-1) represents a single bond or a double bond; A represents a single bond, a bivalent 5- to 14-membered heterocyclic group which may have a substituent and the like; Y represents a single bond and the like; Z represents a methylene group and the like; ring G represents a phenylene group and the like which may condense with a 5- to 6-membered ring and may have a heteroatom; R a and R b are the same as or different from each other and represent a hydrogen atom and the like; W represents a single bond and the like; R′ represents 1 to 4 independent hydrogen atoms and the like; and R″ represents 1 to 4 independent hydrogen atoms and the like] or a salt thereof, or a hydrate thereof.
1. A compound represented by the following formula (I);
wherein
TZ represents a C1-C4 alkylene group or —CR f′ R g′ —CH 2 —O— wherein R f′ and R g′ independently represent a C1-C6 alkyl group;
A represents a 5- to 14-membered heteroarylene group which may have a substituent or a C6-C14 arylene group which may have a substituent;
Y represents —CH 2 —NR c — wherein R c represents a C1-C6 alkyl group which may have a substituent;
ring G represents the following formula;
R′ represents 1 to 4 substituents independently selected from a hydrogen and a C1-C6 alkoxy group;
a partial structure in formula (I) represented by the following formula:
is
R″ represents a hydroxyl group that may be further protected by a protecting group or a C1-C6 alkoxy group which may have a substituent; and
R a and R b are the same as or different from each other and each represents a hydrogen atom, a C1-C6 alkyl group which may have a substituent, or a C3-C8 cycloalkyl group which may have a substituent, or when R a and R b are bonded together, they may form, together with the nitrogen atom that is adjacent to R a and R b , a 4- to 10-membered single ring which may have a substituent; and
L represents a single bond,
or a salt thereof.
2. The compound or the salt thereof, according to claim 1 , wherein R a and R b independently represent a hydrogen atom, a methyl group, an ethyl group, an n-propyl group, an iso-propyl group, an n-butyl group, an iso-butyl group, or a tert-butyl group.
3. The compound or the salt thereof, according to claim 1 , wherein -T-Z represents —CH 2 CH 2 or —C(CH 3 ) 2 CH 2 O—.
4. The compound or the salt thereof, according to claim 1 , wherein Y represents —CH 2 —N(CH 2 CH 3 )— or —CH 2 —N(CH 2 CH 2 OH)—.
5. The compound or the salt thereof, or the hydrate thereof according to claim 1 , wherein each of R″ independently represents a hydrogen atom or a methoxy group.
6. The compound or the salt thereof according to claim 1 , wherein R″ represents a hydroxyl group.
7. The compound or the salt thereof, according to claim 1 , wherein A represents a phenylene group.
8. A compound selected from the group consisting of
(R)-6-{2-{ethyl[4-(2-ethylaminoethyl)benzyl]amino }-4-methoxyphenyl }-5,6,7,8-tetrahydronaphthalen-2-ol,
(R)-6-{2-{ethyl [4-(2-ethylaminoethyl)benzyl]amino }-4,5-dimethoxyphenyl }-5,6,7,8-tetrahydronaphthalen-2-ol,
(R)-6-{2-{ethyl [4-(2-methylaminoethyl)benzyl]amino }-4-methoxyphenyl }-5,6,7,8-tetrahydronaphthalen-2-ol,
(R)-6-{2-[[4-(2-dimethylamino-2-methylpropoxy)benzyl](2-hydroxyethyl)amino]-4-methoxyphenyl }-5 ,6,7,8-tetrahydronaphthalen-2-ol,
(R)-6-{2-{ethyl[4-(2-propylaminoethyl)benzyl]amino }-4-methoxyphenyl }-5,6,7,8-tetrahydronaphthalen-2-ol,
(R)-6-{2-{[4-(2-butylaminoethyl)benzyl]ethylamino }-4-methoxyphenyl }-5,6,7,8-tetrahydronaphthalen-2-ol,
(R)-6-{2-{ethyl [4-(2-isopropylaminoethyl)benzyl]amino }-4-methoxyphenyl }-5,6,7,8-tetrahydronaphthalen-2-ol,
(R)-6-{2-{[4-(2-tert-butylaminoethyl)benzyl]ethylamino }-4-methoxyphenyl }-5,6,7,8-tetrahydronaphthalen-2-ol, and
(R)-6-{2-{[4-(2-cyclohexylaminoethyl)benzyl]ethylamino }-4-methoxyphenyl }-5,6,7,8-tetrahydronaphthalen-2-ol,
or a salt of any of the foregoing.
9. The compound
(R)-6-{2-{ethyl [4-(2-ethylaminoethyl)benzyl]amino }-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-ol,
or a salt thereof.
10. The compound
(R)-6-{2-[[4-(2-dimethylamino-2-methylpropoxy)benzyl](2-hydroxyethyl)amino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-ol,
or a salt thereof.
11. A pharmaceutical composition comprising the compound or the salt thereof according to any one of claims 1 , 2 , and 3 - 10 and a pharmaceutically acceptable carrier.
12. A method for treating osteoporosis, or breast cancer, which are estrogen-dependent, comprising administering to a mammalian animal an effective amount of the compound or the salt thereof, according to any one of claims 1 , 2 , and 3 - 10 .