US2011071146A1PendingUtilityA1
17BetaHSD Type 5 Inhibitor
Est. expiryMar 2, 2026(expired)· nominal 20-yr term from priority
Inventors:Tatsuya NiimiAkio KamikawaYasushi AmanoTomohiko YamaguchiKenichi SuzumuraKentaro EnjoTakashi FurutaniAkio KakefudaYutaka KondohMasaaki Hirano
A61P 43/00A61P 5/24A61P 35/00A61P 5/38C07D 417/12C07D 409/12C07D 413/14A61P 15/00C07D 513/04C07D 409/14C07D 471/04A61P 13/08A61P 17/10A61P 17/08C07D 413/12A61P 17/14A61P 15/08C07D 403/12C07D 401/12C07D 209/08C07D 405/12C07D 491/056C07D 209/42
42
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
To provide a novel and excellent method for treating and/or preventing prostatic cancer, benign prostatic hyperplasia, acne, seborrhea, hirsutism, baldness, alopecia, precocious puberty, adrenal hypertrophy, polycystic ovary syndrome, breast cancer, lung cancer, endometriosis, leiomyoma and the like based on selective inhibitory activity against 17βHSD type 5. It was found that an N-sulfonylindole derivative, where the indole ring is substituted by a carboxy group, a carboxy-substituted lower alkyl group or a carboxy-substituted lower alkenyl group at its carbon atom, has potent selective inhibitory activity against 17βHSD type 5 and may become a therapeutic agent and/or preventive agent for benign prostatic hyperplasia, prostatic cancer and the like without accompanying adverse drug reactions due to a decrease in testosterone, and the present invention has thus been completed.
Claims
exact text as granted — not AI-modified1 - 7 . (canceled)
8 . A method for producing a medicament for a treatment and/or prevention of a disease associated with 17βHSD type 5 comprising admixing a compound of formula (I) or a pharmaceutically acceptable salt thereof:
wherein L represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R aaa , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or aryl amino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O—, heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the R aaa may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 111 , R 222 , R 333 , R 444 , R 555 and R 666 represent hydrogen or an appropriate substituent, in which at least one of the R 111 , R 222 , R 333 , R 444 , R 555 and R 666 represents carboxy, carboxy-substituted lower alkyl or carboxy-substituted lower alkenyl, and any adjacent two groups of R 333 , R 444 , R 555 and R 666 together may form a lower alkylene dioxy group;
a double line of a solid line and a dotted line represents a single bond or a double bond; and
p represents an integer of 1 to 15;
with at least one pharmaceutically acceptable carrier and/or excipient.
9 . A method for producing a medicament for a treatment and/or prevention of prostatic cancer, benign prostatic hyperplasia, acne, seborrhea, hirsutism, baldness, alopecia, precocious puberty, adrenal hypertrophy, polycystic ovary syndrome, breast cancer, endometriosis, lung cancer or leiomyoma comprising admixing a compound of formula (I) or a pharmaceutically acceptable salt thereof:
wherein L represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R aaa , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or aryl amino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O—, heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the R aaa may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 111 , R 222 , R 333 , R 444 , R 555 and R 666 represent hydrogen or an appropriate substituent, in which at least one of the R 111 , R 222 , R 333 , R 444 , R 555 and R 666 represents carboxy, carboxy-substituted lower alkyl or carboxy-substituted lower alkenyl, and any adjacent two groups of R 333 , R 444 , R 555 and R 666 together may form a lower alkylene dioxy group;
a double line of a solid line and a dotted line represents a single bond or a double bond; and
p represents an integer of 1 to 15;
with at least one pharmaceutically acceptable carrier and/or excipient.
10 . A therapeutic and/or preventive method for a disease associated with 17βHSD type 5, comprising administering to a patient in need thereof an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof:
wherein L represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R aaa , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or aryl amino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O—, heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the R aaa may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 111 , R 222 , R 333 , R 444 , R 555 and R 666 represent hydrogen or an appropriate substituent, in which at least one of the R 111 , R 222 , R 333 , R 444 , R 555 and R 666 represents carboxy, carboxy-substituted lower alkyl or carboxy-substituted lower alkenyl, and any adjacent two groups of R 333 , R 444 , R 555 and R 666 together may form a lower alkylene dioxy group;
a double line of a solid line and a dotted line represents a single bond or a double bond; and
p represents an integer of 1 to 15.
11 . A method for treating and/or preventing prostatic cancer, benign prostatic hyperplasia, acne, seborrhea, hirsutism, baldness, alopecia, precocious puberty, adrenal hypertrophy, polycystic ovary syndrome, breast cancer, endometriosis, lung cancer or leiomyoma, comprising administering to a patient in need thereof an effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof:
wherein L represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R aaa , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or aryl amino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O—, heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the R aaa may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 111 , R 222 , R 333 , R 444 , R 555 and R 666 represent hydrogen or an appropriate substituent, in which at least one of the R 111 , R 222 , R 333 , R 444 , R 555 and R 666 represents carboxy, carboxy-substituted lower alkyl or carboxy-substituted lower alkenyl, and any adjacent two groups of R 333 , R 444 , R 555 and R 666 together may form a lower alkylene dioxy group;
a double line of a solid line and a dotted line represents a single bond or a double bond; and
p represents an integer of 1 to 15.
12 - 15 . (canceled)
16 . A method for producing a medicament for a treatment and/or prevention of a disease associated with 17βHSD type 5 comprising admixing a compound of formula (II) or a pharmaceutically acceptable salt thereof:
wherein T represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R aa , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or arylamino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O—, heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the R aa may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 22 , R 33 , R 44 , R 55 and R 66 represent hydrogen or an appropriate substituent, in which at least one of R 22 , R 33 , R 44 , R 55 and R 66 represents carboxy; and
m represents an integer of 1 to 15;
with at least one pharmaceutically acceptable carrier and/or excipient.
17 . A method for producing a medicament for a treatment and/or prevention of prostatic cancer, benign prostatic hyperplasia, acne, seborrhea, hirsutism, baldness, alopecia, precocious puberty, adrenal hypertrophy, polycystic ovary syndrome, breast cancer, endometriosis, lung cancer or leiomyoma comprising admixing a compound of formula (II) or a pharmaceutically acceptable salt thereof:
wherein T represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R aa , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or arylamino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O— heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the R aa may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 22 , R 33 , R 44 , R 55 and R 66 represent hydrogen or an appropriate substituent, in which at least one of R 22 , R 33 , R 44 , R 55 and R 66 represents carboxy; and
m represents an integer of 1 to 15;
with at least one pharmaceutically acceptable carrier and/or excipient.
18 . A therapeutic and/or preventive method for a disease associated with 17βHSD type 5, comprising administering to a patient in need thereof an effective amount of a compound of formula (II) or a pharmaceutically acceptable salt thereof:
wherein T represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R aa , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or arylamino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O—, heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the R aa may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 22 , R 33 , R 44 , R 55 and R 66 represent hydrogen or an appropriate substituent, in which at least one of R 22 , R 33 , R 44 , R 55 and R 66 represents carboxy; and
m represents an integer of 1 to 15.
19 . A method for treating and/or preventing prostatic cancer, benign prostatic hyperplasia, acne, seborrhea, hirsutism, baldness, alopecia, precocious puberty, adrenal hypertrophy, polycystic ovary syndrome, breast cancer, endometriosis, lung cancer or leiomyoma, comprising administering to a patient in need thereof an effective amount of a compound of formula (II) or a pharmaceutically acceptable salt thereof:
wherein T represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R aa , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or arylamino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O—, heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the R aa may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 22 , R 33 , R 44 , R 55 and R 66 represent hydrogen or an appropriate substituent, in which at least one of R 22 , R 33 , R 44 , R 55 and R 66 represents carboxy; and
m represents an integer of 1 to 15.
20 - 35 . (canceled)
36 . A method for producing a medicament for a treatment and/or prevention of a disease associated with 17βHSD type 5 comprising admixing a compound of formula (III) or a pharmaceutically acceptable salt thereof:
wherein A represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R a , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or arylamino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O—, heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the R a may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 2 to R 6 represent hydrogen or an appropriate substituent, in which at least one of R 2 to R 6 represents carboxy, and any adjacent two groups of R 3 to R 6 together may form a lower alkylene dioxy group; and
n represents an integer of 1 to 15;
provided that when R 2 is carboxy, R 3 , R 4 , R 5 and R 6 are hydrogen,
is 1-naphthyl, A is a bond and n is 1; R a is a group other than 4-methoxy;
when R 2 is carboxy, R 3 , R 4 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen and 4-methyl;
when n is 2, a combination of two R a is selected from combinations of groups other than a combination of 4-methyl and 3-nitro and a combination of 3-methoxy and 4-methoxy;
when R 3 is carboxy, R 2 , R 4 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than 4-methyl;
when R 4 is carboxy, R 2 , R 5 and R 6 are hydrogen, R 3 is 2-bromophenyl,
is 2-thienyl, A is a bond, and n is 1; R 1 is a group other than hydrogen;
when R 4 is carboxy, R 2 , R 3 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is 3-methoxycarbonyl-3-hydroxyacryloyl,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is 3-carboxy-3-hydroxyacryloyl,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is acetyl,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 5 is carboxy, R 2 is methyl, R 3 , R 4 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than 4-methyl; and
when R 5 is carboxy, R 2 , R 3 , R 4 and R 6 are hydrogen,
is 8-quinolinyl, A is a bond, and n is 1; R a is a group other than hydrogen;
with at least one pharmaceutically acceptable carrier and/or excipient.
37 . A method for producing a medicament for a treatment and/or prevention of prostatic cancer, benign prostatic hyperplasia, acne, seborrhea, hirsutism, baldness, alopecia, precocious puberty, adrenal hypertrophy, polycystic ovary syndrome, breast cancer, endometriosis, lung cancer or leiomyoma comprising admixing a compound of formula (III) or a pharmaceutically acceptable salt thereof:
wherein A represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R a , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or arylamino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O—, heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the R a may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 2 to R 6 represent hydrogen or an appropriate substituent, in which at least one of R 2 to R 6 represents carboxy, and any adjacent two groups of R 3 to R 6 together may form a lower alkylene dioxy group; and
n represents an integer of 1 to 15;
provided that when R 2 is carboxy, R 3 , R 4 , R 5 and R 6 are hydrogen,
is 1-naphthyl, A is a bond and n is 1; R a is a group other than 4-methoxy; when R 2 is carboxy, R 3 , R 4 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen and 4-methyl;
when n is 2, a combination of two R a is selected from combinations of groups other than a combination of 4-methyl and 3-nitro and a combination of 3-methoxy and 4-methoxy;
when R 3 is carboxy, R 2 , R 4 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond and n is 1; R a is a group other than 4-methyl;
when R 4 is carboxy, R 2 , R 5 and R 6 are hydrogen, R 3 is 2-bromophenyl,
is 2-thienyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 2 , R 3 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is 3-methoxycarbonyl-3-hydroxyacryloyl,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is 3-carboxy-3-hydroxyacryloyl,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is acetyl,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 5 is carboxy, R 2 is methyl, R 3 , R 4 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than 4-methyl; and
when R 5 is carboxy, R 2 , R 3 , R 4 and R 6 are hydrogen,
is 8-quinolinyl, A is a bond, and n is 1; R a is a group other than hydrogen;
with at least one pharmaceutically acceptable carrier and/or excipient.
38 . A method for treating a disease associated with 17βHSD type 5, comprising administering to a patient in need thereof an effective amount of a compound of formula (III) or a pharmaceutically acceptable salt thereof:
wherein A represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R a , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or arylamino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O—, heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 2 to R 6 represent hydrogen or an appropriate substituent, in which at least one of R 2 to R 6 represents carboxy, and any adjacent two groups of R 3 to R 6 together may form a lower alkylene dioxy group; and
n represents an integer of 1 to 15;
provided that when R 2 is carboxy, R 3 , R 4 , R 5 and R 6 are hydrogen,
is 1-naphthyl, A is a bond and n is 1; R a is a group other than 4-methoxy;
when R 2 is carboxy, R 3 , R 4 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen and 4-methyl;
when n is 2, a combination of two R a is selected from combinations of groups other than a combination of 4-methyl and 3-nitro and a combination of 3-methoxy and 4-methoxy;
when R 3 is carboxy, R 2 , R 4 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than 4-methyl;
when R 4 is carboxy, R 2 , R 5 and R 6 are hydrogen, R 3 is 2-bromophenyl,
is 2-thienyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 2 , R 3 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is 3-methoxycarbonyl-3-hydroxyacryloyl,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is 3-carboxy-3-hydroxyacryloyl,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is acetyl,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 5 is carboxy, R 2 is methyl, R 3 , R 4 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than 4-methyl; and
when R 5 is carboxy, R 2 , R 3 , R 4 and R 6 are hydrogen,
is 8-quinolinyl, A is a bond, and n is 1; R a is a group other than hydrogen.
39 . A method for treating and/or preventing prostatic cancer, benign prostatic hyperplasia, acne, seborrhea, hirsutism, baldness, alopecia, precocious puberty, adrenal hypertrophy, polycystic ovary syndrome, breast cancer, endometriosis, lung cancer or leiomyoma, comprising administering to a patient in need thereof an effective amount of a compound of formula (III) or a pharmaceutically acceptable salt thereof:
wherein A represents lower alkylene, lower alkenylene, —O-lower alkylene, lower alkylene-O— or a bond, in which each of the groups may be substituted by aryl(s);
represents an aryl, cycloalkyl or heterocyclic group;
R a , which is the same or different, represents hydrogen, lower alkyl, halogen, cyano, lower alkenyl, halogen-substituted lower alkyl, lower alkyl-O—, cyano lower alkyl-O—, halogen-substituted lower alkyl-O—, aryl, heteroaryl, aryl-O—, heteroaryl-O—, aryl lower alkyl, acyl-O—, acyl, heteroaryl lower alkyl-O—, lower alkylthio, lower alkylsulfonyl, oxo, nitro, amino, mono-lower alkylamino, di-lower alkylamino, acylamino or arylamino, in which the aryl, the heteroaryl, and the aryl and the heteroaryl moieties of each of the aryl-O—, heteroaryl-O—, heteroaryl lower alkyl-O—, aryl lower alkyl and arylamino in the R a may be substituted by lower alkyl(s), lower alkyl-O-(s), halogen(s) or halogen-substituted lower alkyl(s);
R 2 to R 6 represent hydrogen or an appropriate substituent, in which at least one of R 2 to R 6 represents carboxy, and any adjacent two groups of R 3 to R 6 together may form a lower alkylene dioxy group; and
n represents an integer of 1 to 15;
provided that when R 2 is carboxy, R 3 , R 4 , R 5 and R 6 are hydrogen,
is 1-naphthyl, A is a bond and n is 1; R a is a group other than 4-methoxy;
when R 2 is carboxy, R 3 , R 4 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen and 4-methyl;
when n is 2, a combination of two R a is selected from combinations of groups other than a combination of 4-methyl and 3-nitro and a combination of 3-methoxy and 4-methoxy;
when R 3 is carboxy, R 2 , R 4 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than 4-methyl;
when R 4 is carboxy, R 2 , R 5 and R 6 are hydrogen, R 3 is 2-bromophenyl,
is 2-thienyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 2 , R 3 , R 5 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is 3-methoxycarbonyl-3-hydroxyacryloyl,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is 3-carboxy-3-hydroxyacryloyl,
is phenyl, A is a bond, and n is 1; R 2 is a group other than hydrogen;
when R 4 is carboxy, R 3 , R 5 and R 6 are hydrogen, R 2 is acetyl,
is phenyl, A is a bond, and n is 1; R a is a group other than hydrogen;
when R 5 is carboxy, R 2 is methyl, R 3 , R 4 and R 6 are hydrogen,
is phenyl, A is a bond, and n is 1; R a is a group other than 4-methyl; and
when R 5 is carboxy, R 2 , R 3 , R 4 and R 6 are hydrogen,
is 8-quinolinyl, A is a bond, and n is 1; R a is a group other than hydrogen.
40 - 41 . (canceled)Join the waitlist — get patent alerts
Track US2011071146A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.