Hetero-fused cyclic compound

Patent metadata

Field	Value
Publication number	US-2016168176-A1
Application number	US-201414904860-A
Country	US
Kind code	A1
Filing date	Jul 18, 2014
Priority date	Jul 23, 2013
Publication date	Jun 16, 2016
Grant date	—

Abstract

A compound represented by the formula (I) or a salt thereof:

wherein a ring Z is a 5 to 6-membered heteroaromatic ring having one or two heteroatoms in the ring; X 1 is a hydrogen atom, a hydroxy group, a hydroxy C 1-6 alkyl group, —B(OH) 2 , a boronate ester group, a cyclic boronate ester group, a boranyl group, a cyclic boranyl group, —BF 3 M n1 , —Sn(R 12 )(R 13 )(R 14 ), a leaving group, a carboxy group, a formyl group, or —NR 16 R 17 ; and X 2 is a hydrogen atom or —CO 2 R 18 .

First claim

1 . A compound represented by the formula (I) or a salt thereof:

wherein the ring Z is a 5- or 6-membered heteroaromatic ring having one or two heteroatoms in the ring;
X 1 is a hydrogen atom, a hydroxy group, a hydroxy C 1-6 alkyl group, —B(OH) 2 , a boronate ester group, a cyclic boronate ester group, a boranyl group, a cyclic boranyl group, —BF 3 M n1 wherein n1 is 0 or 1 and M is an alkali metal, —Sn(R 12 )(R 13 )(R 14 ) wherein R 12 , R 13 , and R 14 are the same or different and are a C 1-6 alkyl group, -L wherein L is a leaving group, a carboxy group, a formyl group, or —NR 16 R 17 wherein R 16 and R 17 are the same or different and are a hydrogen atom, a C 1-6 alkyl group, or a protecting group for an amino group, or is a protecting group for an amino group with the nitrogen atom bonded to R 16 and R 17 ; and
X 2 is a hydrogen atom or —CO 2 R 18 wherein R 18 is a hydrogen atom, a C 1-6 alkyl group, or a protecting group for a carboxy group;
provided that a case wherein X 1 and X 2 are hydrogen atoms at the same time and the following compounds are excluded:
5,7-dihydro-furo[3,4-b]pyridin-3-amine,
5,7-dihydro-furo[3,4-b]pyridin-2(1H)-one,
3-bromo-5,7-dihydro-furo[3,4-b]pyridine,
5,7-dihydro-furo[3,4-b]pyridine-2-carboxylic acid,
5,7-dihydro-furo[3,4-b]pyridine-3-carboxylic acid,
1,3-dihydro-furo[3,4-c]pyridine-6-carboxaldehyde,
1,3-dihydro-furo[3,4-c]pyridin-6-ylmethanol,
3,4-dihydro-furo[3,4-b]pyrazin-2(1H)-one,
4-chloro-5,7-dihydro-furo[3,4-d]pyrimidine,
2-chloro-5,7-dihydro-furo[3,4-d]pyrimidine,
5,7-dihydro-furo[3,4-d]pyridazin-1(2H)-one,
2-bromo-4,6-dihydro-thieno[2,3-c]furan,
3-bromo-4,6-dihydro-thieno[2,3-c]furan,
4,6-dihydro-furo[3,4-b]furan-3-carboxylic acid,
4,6-dihydro-1H-furo[3,4-c]pyrazole-3-carboxylic acid,
3-bromo-4,6-dihydro-furo[3,4-d]isoxazole, and
4,6-dihydro-furo[3,4-d]isoxazole-3-carboxylic acid.

2 . The compound or the salt thereof according to claim 1 , wherein the compound or the salt thereof is a compound represented by the formula (II) or a salt thereof:

wherein the ring Z1 is a 5-membered heteroaromatic ring having one or two heteroatoms in the ring; and
X 1 and X 2 are the same as defined as in claim 1 ;
provided that a case wherein X 1 and X 2 are hydrogen atoms at the same time and the following compounds are excluded:
2-bromo-4,6-dihydro-thieno[2,3-c]furan,
3-bromo-4,6-dihydro-thieno[2,3-c]furan,
4,6-dihydro-furo[3,4-b]furan-3-carboxylic acid,
4,6-dihydro-1H-furo[3,4-c]pyrazole-3-carboxylic acid,
3-bromo-4,6-dihydro-furo[3,4-d]isoxazole, and
4,6-dihydro-furo[3,4-d]isoxazole-3-carboxylic acid.

3 . The compound or the salt thereof according to claim 2 , wherein the ring Z1 is a thiophene ring, a furan ring, a pyrrolidine ring, a thiazole ring, an oxazole ring, an imidazole ring, an isothiazole ring, an isoxazole ring, or a pyrazole ring in the compound represented by the formula (II) or the salt thereof.

4 . The compound or the salt thereof according to claim 2 , wherein the fused ring consisting of the ring Z1 and the adjacent ring thereto is a thieno[2,3-c]furan ring, a furo[2,3-c]furan ring, a furo[3,4-b]pyrrole ring, a furo[3,4-d]thiazole ring, a furo[3,4-d]oxazole ring, a furo[3,4-d]imidazole ring, a furo[3,4-d]isothiazole ring, a furo[3,4-d]isoxazole ring, or a furo[3,4-c]pyrazole ring in the compound represented by the formula (II) or the salt thereof.

5 . The compound or the salt thereof according to claim 1 , wherein the compound or the salt thereof is a compound represented by the formula (III) or a salt thereof:

wherein the ring Z2 is a 6-membered heteroaromatic ring having one or two heteroatoms in the ring; and X 1 and X 2 are the same as defined as in claim 1 ;
provided that a case wherein X 1 and X 2 are hydrogen atoms at the same time and the following compounds are excluded:
5,7-dihydro-furo[3,4-b]pyridin-3-amine,
5,7-dihydro-furo[3,4-b]pyridin-2(1H)-one,
3-bromo-5,7-dihydro-furo[3,4-b]pyridine,
5,7-dihydro-furo[3,4-b]pyridine-2-carboxylic acid,
5,7-dihydro-furo[3,4-b]pyridine-3-carboxylic acid,
1,3-dihydro-furo[3,4-c]pyridine-6-carboxaldehyde,
1,3-dihydro-furo[3,4-c]pyridin-6-ylmethanol,
3,4-dihydro-furo[3,4-b]pyrazin-2(1H)-one,
4-chloro-5,7-dihydro-furo[3,4-d]pyrimidine,
2-chloro-5,7-dihydro-furo[3,4-d]pyrimidine, and
5,7-dihydro-furo[3,4-d]pyridazin-1(2H)-one.

6 . The compound represented by the formula (III) or the salt thereof according to claim 5 , wherein the ring Z2 is a pyridine ring, a pyrazine ring, a pyrimidine ring, or a pyridazine ring.

7 . The compound or the salt thereof according to claim 5 , wherein the fused ring consisting of the ring Z2 and the adjacent ring is a furo[3,4-b]pyridine ring, a furo[3,4-c]pyridine ring, a furo[3,4-b]pyrazine ring, a furo[3,4-d]pyrimidine ring, a furo[3,4-c]pyridazine ring, or a furo[3,4-d]pyridazine ring in the compound represented by the formula (III) or the salt thereof.

8 . The compound or the salt thereof according to claim 1 , wherein X 1 is —B(OH) 2 , a boronate ester group, a cyclic boronate ester group, —BF 3 M n1 wherein n1 is 0 or 1 and M is an alkali metal, —Sn(R 12 )(R 13 )(R 14 ) wherein R 13 , and R 14 are the same or different and are a C 1-6 alkyl group, or -L wherein L is a leaving group.

9 . The compound or the salt thereof according to claim 8 , wherein the leaving group is a halogen atom, a methanesulfonyloxy group, a p-toluenesulfonyloxy group, or a trifluoromethanesulfonyloxy group.

10 . The compound or the salt thereof according to claim 1 , wherein the boronate ester group is a substituent represented by the formula (Y-1),
the cyclic boronate ester group is a substituent represented by the formulae (Y-2) to (Y-13), the boranyl group is a substituent represented by the formula (Y-14), and the cyclic boranyl group is a substituent represented by the formula (Y-15):

wherein R 1 to R 10 are the same or different and are a C 1-6 alkyl group.

11 . The compound or the salt thereof according to claim 1 , wherein the compound or the salt thereof is a compound listed below:
1,2,5,7-tetrahydro-furo[3,4-d]pyridazin-1-one, methyl 4,6-dihydrofuro[3,4-b]furan-2-carboxylate, 4,6-dihydrofuro[3,4-b]furan-2-carboxylic acid, 4,6-dihydrothieno[2,3-c]furan-2-carbaldehyde, (4,6-dihydrothieno[2,3-c]furan-2-yl)methanol, 2-amino-5,7-dihydrofuro[3,4-b]pyrazine, 2-amino-5,7-dihydrofuro[3,4-b]pyridine, methyl 4,6-dihydro-1H-furo[3,4-b]pyrrole-2-carboxylate, tert-butyl N-[(tert-butoxy)carbonyl]-N-{1,3-dihydrofuro[3,4-c]pyridin-6-yl}carbamate, methyl 4,6-dihydrofuro[3,4-d]isothiazole-3-carboxylate, methyl 3-amino-5,7-dihydrofuro[3,4-b]pyrazine-2-carboxylate, methyl 3-hydroxy-4,6-dihydrothieno[2,3-c]furan-2-carboxylate, 2-chloro-4,6-dihydrothieno[2,3-c]furan, 4-amino-5,7-dihydrofuro[3,4-d]pyrimidine, 1-bromo-5,7-dihydrofuro[3,4-d]pyrid

Assignees

• Eisai R&D Man Co Ltd
• Eisai R&D Man Co Lt D

Inventors

• Tanaka Keigo
• Fukuyama Takashi
• Murai Norio
• Itano Wataru
• Hirota Shinsuke
• Iida Daisuke
• Azuma Hiroshi

Classifications

• A61P31/10

  Antimycotics · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• C07F5/02

  Boron compounds · CPC title

• C07F7/2208 Primary

  Compounds having tin linked only to carbon, hydrogen and/or halogen · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title