US 2012/0071486 A1Published application

Thienopyrimidine compounds and use thereof

AssigneeTakeda Pharmaceutical Company Limited

InventorsNobuo Cho, Takashi Imada, Takenori Hitaka, Kazuhiro Miwa, Masami Kusaka, Nobuhiro Suzuki

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Abstract

The present invention provides a compound represented by the formula: wherein R1 is a C1-4 alkyl; R2 is (1) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a hydroxy group, (3′) a C1-4 alkyl and (4′) a C1-4 alkoxy, (2) a phenyl which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a C1-4 alkoxy-C1-4 alkyl, (3′) a mono-C1-4 alkyl-carbamoyl-C1-4 alkyl, (4′) a C1-4 alkoxy and (5′) a mono-C1-4 alkylcarbamoyl-C1-4 alkoxy, or the like; R3 is a C1-4 alkyl; R4 is a C1-4 alkoxy, or the like; n is an integer of 1 to 4; or a salt thereof, as a thienopyrimidine compound having gonadotropin-releasing hormone antagonistic activity.

Claims4

Dependent claims

A method for antagonizing gonadotropin-releasing hormone, which comprises administering an effective amount of the compound represented by formula (I):

wherein
R1 is a C1-4 alkyl;
R2 is
(1) a C1-6 alkyl which may have a substituent selected from the group consisting of (1′) a hydroxy group, (2′) a C1-4 alkoxy, (3′) a C1-4 alkoxy-carbonyl, (4′) a di-C1-4 alkyl-carbamoyl, (5′) a 5- to 7-membered nitrogen-containing heterocyclic group, (6′) a C1-4 alkyl-carbonyl and (7′) a halogen,
(2) a C3-8 cycloalkyl which may have (1′) a hydroxy group or (2′) a mono-C1-4 alkyl-carbonylamino,
(3) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a hydroxy group, (3′) a C1-4 alkyl and (4′) a C1-4 alkoxy,
(4) a phenyl which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a C1-4 alkoxy-C1-4 alkyl, (3′) a mono-C1-4 alkyl-carbamoyl-C1-4 alkyl, (4′) a C1-4 alkoxy and (5′) a mono-C1-4 alkyl-carbamoyl-C1-4 alkoxy, or
(5) a C1-4 alkoxy;
R3 is a C1-4 alkyl;
R4 is
(1) a hydrogen atom,
(2) a C1-4 alkoxy,
(3) a C6-10 aryl,
(4) a N—C1-4 alkyl-N—C1-4 alkylsulfonylamino,
(5) a hydroxyl group, or
(6) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) oxo, (2′) a C1-4 alkyl, (3′) a hydroxy-C1-4 alkyl, (4′) a C1-4 alkoxy-carbonyl, (5′) a mono-C1-4 alkyl-carbamoyl and (6′) a C1-4 alkylsulfonyl;
n is an integer of 1 to 4;
provided that when R2 is a phenyl which may have a substituent, R4 is a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1) oxo, (2) a hydroxy-C1-4 alkyl, (3) a C1-4 alkoxy-carbonyl, (4) a mono-C1-4 alkyl-carbamoyl and (5) a C1-4 alkylsulfonyl;
or a salt thereof to a mammal.

16 more elements

A method for preventing and/or treating diseases selected from the group consisting of sex-hormone dependent cancers, bone metastasis of the sex hormone-dependent cancers, prostatic hypertrophy, hysteromyoma, endometriosis, metrofibroma, precocious puberty, amenorrhea, premenstrual syndrome, dysmenorrhea, multilocular ovary syndrome, polycystic ovary syndrome, acne, alopecia, Alzheimer's disease, infertility, irritable bowel syndrome and LH-RH sensitive benign or malignant tumor which is independent of the hormone;

for regulating reproduction, contraception or induction of ovulation;
or for preventing postoperative recurrence of sex hormone-dependent cancers, by antagonizing gonadotropin-releasing hormone, which comprises administering an effective amount of the compound represented by formula (I):
wherein
R1 is a C1-4 alkyl;
R2 is
(1) a C1-6 alkyl which may have a substituent selected from the group consisting of (1′) a hydroxy group, (2′) a C1-4 alkoxy, (3′) a C1-4 alkoxy-carbonyl, (4′) a di-C1-4 alkyl-carbamoyl, (5′) a 5- to 7-membered nitrogen-containing heterocyclic group, (6′) a C1-4 alkyl-carbonyl and (7′) a halogen,
(2) a C3-8 cycloalkyl which may have (1′) a hydroxy group or (2′) a mono-C1-4 alkyl-carbonylamino,
(3) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a hydroxy group, (3′) a C1-4 alkyl and (4′) a C1-4 alkoxy,
(4) a phenyl which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a C1-4 alkoxy-C1-4 alkyl, (3′) a mono-C1-4 alkyl-carbamoyl-C1-4 alkyl, (4′) a C1-4 alkoxy and (5′) a mono-C1-4 alkyl-carbamoyl-C1-4 alkoxy, or
(5) a C1-4 alkoxy;
R3 is a C1-4 alkyl;
R4 is
(1) a hydrogen atom,
(2) a C1-4 alkoxy,
(3) a C6-10 aryl,
(4) a N—C1-4 alkyl-N—C1-4 alkylsulfonylamino,
(5) a hydroxyl group, or
(6) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) oxo, (2′) a C1-4 alkyl, (3′) a hydroxy-C1-4 alkyl, (4′) a C1-4 alkoxy-carbonyl, (5′) a mono-C1-4 alkyl-carbamoyl and (6′) a C1-4 alkylsulfonyl;
n is an integer of 1 to 4;
provided that when R2 is a phenyl which may have a substituent, R4 is a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1) oxo, (2) a hydroxy-C1-4 alkyl, (3) a C1-4 alkoxy-carbonyl, (4) a mono-C1-4 alkyl-carbamoyl and (5) a C1-4 alkylsulfonyl;
or a salt thereof;
to a mammal.

19 more elements

A method for preventing and/or treating diseases depending on male or female hormone, diseases due to excess of these hormones, by suppressing gonadotropin secretion with its gonadotropin-releasing hormone receptor-antagonizing action to control plasma sex hormone concentrations, which comprises administering an effective amount of the compound represented by formula (I):

wherein
R1 is a C1-4 alkyl;
R2 is
(1) a C1-6 alkyl which may have a substituent selected from the group consisting of (1′) a hydroxy group, (2′) a C1-4 alkoxy, (3′) a C1-4 alkoxy-carbonyl, (4′) a di-C1-4 alkyl-carbamoyl, (5′) a 5- to 7-membered nitrogen-containing heterocyclic group, (6′) a C1-4 alkyl-carbonyl and (7′) a halogen,
(2) a C3-8cycloallyl which may have (1′) a hydroxy group or (2′) a mono-C1-4 alkyl-carbonylamino,
(3) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a hydroxy group, (3′) a C1-4 alkyl and (4′) a C1-4 alkoxy,
(4) a phenyl which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a C1-4 alkoxy-C1-4 alkyl, (3′) a mono-C1-4 alkyl-carbamoyl-C1-4 alkyl, (4′) a C1-4 alkoxy and (5′) a mono-C1-4 alkyl-carbamoyl-C1-4 alkoxy, or
(5) a C1-4 alkoxy;
R3 is a C1-4 alkyl;
R4 is
(1) a hydrogen atom,
(2) a C1-4 alkoxy,
(3) a C6-10 aryl,
(4) a N—C1-4 alkyl-N—C1-4 alkylsulfonylamino,
(5) a hydroxyl group, or
(6) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) oxo, (2′) a C1-4 alkyl, (3′) a hydroxy-C1-4 alkyl, (4′) a C1-4 alkoxy-carbonyl, (5′) a mono-C1-4 alkyl-carbamoyl and (6′) a C1-4 alkylsulfonyl;
n is an integer of 1 to 4;
provided that when R2 is a phenyl which may have a substituent, R4 is a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1) oxo, (2) a hydroxy-C1-4 alkyl, (3) a C1-4 alkoxy-carbonyl, (4) a mono-C1-4 alkyl-carbamoyl and (5) a C1-4 alkylsulfonyl;
or a salt thereof;
to a mammal.

17 more elements

A method for preventing and/or treating diseases depending on sex hormone, LH-RH sensitive benign or malignant tumor which is independent of the hormone or irritable bowel syndrome;

for regulating reproduction in male or females, male or female contraception, induction of ovulation, or animal estrus;
for preventing postoperative recurrence of sex hormone-dependent cancers;
for improving meat quality;
or for promoting animal growth or fish spawning, which comprises administering an effective amount of the compound represented by formula (I):
wherein
R1 is a C1-4 alkyl;
R2 is
(1) a C1-6 alkyl which may have a substituent selected from the group consisting of (1′) a hydroxy group, (2′) a C1-4 alkoxy, (3′) a C1-4 alkoxy-carbonyl, (4′) a di-C1-4 alkyl-carbamoyl, (5′) a 5- to 7-membered nitrogen-containing heterocyclic group, (6′) a C1-4 alkyl-carbonyl and (7′) a halogen,
(2) a C3-8 cycloalkyl which may have (1′) a hydroxy group or (2′) a mono-C1-4 alkyl-carbonylamino,
(3) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a hydroxy group, (3′) a C1-4 alkyl and (4′) a C1-4 alkoxy,
(4) a phenyl which may have a substituent selected from the group consisting of (1′) a halogen, (2′) a C1-4 alkoxy-C1-4 alkyl, (3′) a mono-C1-4 alkyl-carbamoyl-C1-4 alkyl, (4′) a C1-4 alkoxy and (5′) a mono-C1-4 alkyl-carbamoyl-C1-4 alkoxy, or
(5) a C1-4 alkoxy;
R3 is a C1-4 alkyl;
R4 is
(1) a hydrogen atom,
(2) a C1-4 alkoxy,
(3) a C6-10 aryl,
(4) a N—C1-4 alkyl-N—C1-4 alkylsulfonylamino,
(5) a hydroxyl group, or
(6) a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1′) oxo, (2′) a C1-4 alkyl, (3′) a hydroxy-C1-4 alkyl, (4′) a C1-4 alkoxy-carbonyl, (5′) a mono-C1-4 alkyl-carbamoyl and (6′) a C1-4 alkylsulfonyl;
n is an integer of 1 to 4;
provided that when R2 is a phenyl which may have a substituent, R4 is a 5- to 7-membered nitrogen-containing heterocyclic group which may have a substituent selected from the group consisting of (1) oxo, (2) a hydroxy-C1-4 alkyl, (3) a C1-4 alkoxy-carbonyl, (4) a mono-C1-4 alkyl-carbamoyl and (5) a C1-4 alkylsulfonyl;
or a salt thereof;
to a mammal.

21 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/242,541Filed 23 Sep 2011
Priority: JP 2003-02085429 Jan 2003
Published: 22 Mar 2012
Term ends: Not estimatedThe source records don’t support an estimate.

Classification26 codes

C07D 495/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61K 31/519
Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim: ortho- or peri-condensed with heterocyclic rings
A61P 1/00
Drugs for disorders of the alimentary tract or the digestive system
A61P 1/04
Drugs for disorders of the alimentary tract or the digestive system: for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of…

Family

Application10/544,069Division · filed 29 Jul 2005
Application11/848,939Division · filed 31 Aug 2007
Application13/242,541Division
US 2006/0160829 A1Published application
US 2008/0108623 A1Published application
US 7,300,935 B2Related patent
US 8,058,280 B2Related patent
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US 2012/0071486 A1This patent

From the US filing history. Foreign family members aren’t listed.