US 7,067,537 B2 · Substituted thiazole derivatives bearing 3-pyridyl groups, process for preparing the same and use thereof

Abstract

The present invention provides a pharmaceutical composition having a steroid C17,20-lyase inhibitory activity, which is useful as a prophylactic or therapeutic agent of prostatism, tumor such as breast cancer and the like, more particularly, a steroid C17,20-lyase inhibitor containing a compound represented by the formula: wherein A1 is an aromatic hydrocarbon group optionally having substituents or a heterocyclic group optionally having substituents, one of A2 and A3 is a hydrogen atom, a halogen atom, a C1-4 aliphatic hydrocarbon group optionally having substituents or an optionally esterified carboxyl group, the other of A2 and A3 is an aromatic hydrocarbon group optionally having substituents or a heterocyclic group optionally having substituents, and at least one of A1, A2 and A3 is a 3-pyridyl group optionally having substituents, or a salt thereof or a prodrug thereof.

Claims21

Dependent claims

A compound represented by the formula:

wherein
n is an integer of 1 to 5,
R1c is a carbamoyl group optionally having substituents selected from the group consisting of a C1-6 alkyl and a C6-14 aryl, or an alkylsulfonyl group optionally having halogen atom as a substituent, or two R1c substituting adjacent carbon atoms are bonded to designate a C1-2 alkylenedioxy group, and when n is not less than 2, R1c in the number of n are the same or different,
m is an integer of 1 to 5,
R2 is 1) a hydrogen atom, 2) a C1-4 aliphatic hydrocarbon group optionally having substitutents selected from the group consisting of halogen atom, a hydroxy and carboxy, 3) a carboxyl group optionally esterified by C1-6 alkyl group, 4) a carbamoyl group optionally having substitutents selected from a C1-6 alkyl and a C6-14 aryl, 5) an amino group optionally having substitutents selected from the group consisting of a C1-6 alkyl, a C6-14 aryl, a formyl, a C1-6 alkyl-carbonyl, a C1-4 aryl-carbonyl, a C1-6 alkoxy-carbonyl, a C1-6 alkylsulfonyl and a C6-14 arylsulfonyl, 6) an unsubstituted C1-6 alkylthio, optionally halogenated C1-6 alkylthio or a C7-16 aralkylthio, or 7) an optionally halogenated C1-6 alkoxy group or a C1-6 alkoxy-carbonyl-C1-6 alkoxy group, or two R2 substituting adjacent carbon atoms may be bonded to form 8) a saturated or unsaturated divalent C3-5 carbon chain, and when m is not less than 2, R2 in the number of m may be the same or different, and
R3 is 1) a hydrogen atom, 2) a halogen atom, 3) a C1-4 aliphatic hydrocarbon group optionally having sub stituents selected from the group consisting of halogen atom, a hydroxy and carboxy or 4) a carboxyl group optionally esterified by C1-6 alkyl group,
or a salt thereof.

4 more elements

A compound represented by the formula:

wherein
n is an integer of 1 to 5,
R1c is a carbamoyl group optionally having substituents selected from the group consisting of a C1-6 alkyl and a C6-14 aryl, or an alkylsulfonyl group optionally having a halogen atom as a substituent, or two R1c substituting adjacent carbon atoms are bonded to designate a C1-2 alkylenedioxy group, and when n is not less than 2, R1c in the number of n are the same or different,
R2a and R2b are the same or different and each is 1) a hydrogen atom, 2) a C1-4 aliphatic hydrocarbon group optionally having substituents selected from the group consisting of halogen atom, a hydroxy and carboxy, 3) a carboxyl group optionally esterified by C1-6 alkyl group, 4) a carbamoyl group optionally having substituents selected from the group consisting a C1-6 alkyl and a C6-14 aryl, 5) an amino group optionally having substituents selected from the group consisting of a C1-6 alkyl, a C6-14 aryl, a formyl, a C1-6 alkyl-carbonyl, a C6-14 aryl-carbonyl, a C1-6 alkoxy-carbonyl, a C1-6 alkylsulfonyl and a C6-14 arylsulfonyl, 6) an unsubstituted C1-6 alkylthio, optionally halogenated C1-6 alkylthio or a C7-16 aralkylthio or 7) an optionally halogenated C1-6 alkoxy group or a C1-6 alkoxy-carbonyl-C1-6 alkoxy group, or R2a and R2b may be bonded to form 8) a saturated or unsaturated divalent C3-5 carbon chain, and
R3 is 1) a hydrogen atom, 2) a halogen atom, 3) a C1-4 aliphatic hydrocarbon group optionally having substituents selected from the group consisting of halogen atom, a hydroxy and carboxy or 4) a carboxyl group optionally esterified by C1-6 alkyl group,
or a salt thereof.

3 more elements

A compound represented by the formula:

wherein
n is an integer of 1 to 5,
R1b is 1) a sulfamoyl group optionally having a C1-6 alkyl or a C7-15 aralkyl as a substituent, 2) a carbamoyl group optionally having substituents selected from the group consisting of a C1-6 alkyl and a C6-14 aryl, 3) an alkyl group optionally having a halogen atom or a hydroxy as a substituent, 4) a carboxyl group optionally esterified by C1-6 alkyl group, 5) a halogen atom, 6) an ammo group optionally having substituents selected from the group consisting of a C1-6 alkyl, a C6-14 aryl, a formyl, a C1-6 alkyl-carbonyl, a C6-14 aryl-carbonyl, a C1-6 alkoxy-carbonyl, a C1-6 alkylsulfonyl and a C6-14 arylsulfonyl, 7) a nitro group, 8) an unsubstituted hydroxy, optionally halogenated C1-8 alkoxy, a C1-6 alkoxy-carbonyl-C1-6 alkoxy, a C6-14 aryloxy, a C7-16 aralkyloxy, a C1-6 alkyl-carbonyloxy, a C6-14 aryl-carbonyloxy, a C1-6 alkoxy-carbonyloxy, a mono-C1-6 alkyl-carbamoyloxy, a di-C1-6 alkyl-carbamoyloxy, or a C6-14 aryl-carbamoyloxy, or 9) an alkylsulfonyl group optionally having halogen atom as a substituent, or two R1b substituting adjacent carbon atoms are bonded to designate a C1-2 alkylenedioxy group, and when n is not less than 2, R1b in the number of n may be the same or different, and
R3 is 1) a hydrogen atom, 2) a halogen atom, 3) a C1-4 aliphatic hydrocarbon group optionally having substituents selected from the group consisting of halogen atom, a hydroxy and carboxy or 4) a carboxyl group optionally esterified by C1-6 alkyl group,
or a salt thereof.

2 more elements

A compound represented by the formula:

wherein
p is 0 or an integer of 1 to 5,
Ra and Rb
are the same or different and each is a hydrogen atom or a C1-6 lower alkyl group,
R1d is 1) a hydrogen atom, 2) a C1-4 aliphatic hydrocarbon group optionally having substituents selected from the group consisting of halogen atom, a hydroxy and carboxy, 3) a sulfamoyl group optionally having substituents selected from the group consisting of a C1-6 alkyl and a C7-15 aralkyl, 4) a carbamoyl group optionally having substituents selected from the group consisting of a C1-6 alkyl and a C6-14 aryl, 5) a carboxyl group optionally esterified by C1-6 alkyl group, 6) a halogen atom, 7) an amino group optionally having substituents selected from the group consisting of a C1-6 alkyl, a C6-14 aryl, a formyl, a C1-6 alkyl-carbonyl, a C6-14 aryl-carbonyl, a C1-6 alkoxy-carbonyl, a C1-6 alkylsulfonyl and a C6-14 arylsulfonyl, 8) an unsubstituted hydroxyl, optionally halogenated C1-8 atkoxy, a C1-6 alkoxy-carbonyl-C1-6 alkoxy, a C6-14 aryloxy, a C7-16 aralkyloxy, a C1-6 alkyl-carbonyloxy, a C6-14 aryl-carbonyloxy, a C1-6 alkoxy-carbonyloxy, a mono-C1-6 alkyl-carbamoyloxy, a di-C1-6 alkyl-carbamoyloxy and a C6-14 aryl-carbamoyloxy, 9) an unsubstituted C1-6 alkylthio, optionally halogenated C1-6 alkylthio or a C7-16 aralkylthio, 10) a nitro group, 11) an alkylsulfonyl group optionally having halogen atom as a substituent, or 12) two R1d substituting adjacent carbon atoms maybe bonded to form 12a) a C1-2 alkylenedioxy group or 12b) a saturated or unsaturated divalent C3-5 carbon chain, and when p is not less than 2, R1d in the number of p may be the same or different, and
R3 is 1) a hydrogen atom, 2) a halogen atom, 3) a C1-4 aliphatic hydrocarbon group optionally having substituents selected from the group consisting of halogen atom, a hydroxy and carboxy or 4) a carboxyl group optionally esterified by C1-6 alkyl group,
or a salt thereof.

4 more elements

Dependencies are inferred from the claim text.

Substituted thiazole derivatives bearing 3-pyridyl groups, process for preparing the same and use thereof

Life of this patent

Substituted thiazole derivatives bearing 3-pyridyl groups, process for preparing the same and use thereof

Life of this patent

Abstract

Claims21