Condensed heterocyclic compound

Patent metadata

Field	Value
Publication number	US-9975903-B2
Application number	US-201515539607-A
Country	US
Kind code	B2
Filing date	Dec 24, 2015
Priority date	Dec 26, 2014
Publication date	May 22, 2018
Grant date	May 22, 2018

Abstract

The present invention relates to a condensed heterocyclic compound that has an enteropeptidase inhibitory effect and is useful in the treatment or prevention of obesity, diabetes mellitus, or the like, and a medicament containing the same. Specifically, the present invention relates to a compound represented by the following formula (I) or a salt thereof, and a medicament containing the same [in the formula, each symbol is as defined in the specification].

First claim

The invention claimed is:

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

wherein
ring A represents an optionally substituted 5- or 6-membered aromatic ring, and the substituent of ring A optionally forms an optionally substituted ring together with constituent atoms of ring A;
L represents a bond or a C 1-6 alkylene group;
X 1 and X 2 are the same or different and each represent —O— or a bond;
R represents a guanidino group or an amidino group;
one of Y 1 and Y 2 is —O—, and the other moiety is a bond, provided that when R is a guanidino group, Y 1 represents a bond and Y 2 represents —O—, and when R is an amidino group, Y 1 represents —O— and Y 2 represents a bond.

2. The compound according to claim 1 or a salt thereof, wherein
ring A is
(1) a benzene ring optionally substituted by 1 to 3 substituents selected from
1) a halogen atom,
2) a carboxy group,
3) a cyano group,
4) a carbamoyl group optionally substituted by a C 6-14 aryl group optionally substituted by 1 to 3 substituents selected from a sulfo group; and a C 1-6 alkyl group optionally substituted by a mono- or di-C 1-6 alkylphosphono group,
5) 3- to 14-membered nonaromatic heterocyclylcarbonyl optionally substituted by 1 to 3 substituents selected from a carboxy group; and/or a mono- or di-C 1-6 alkyl-carbamoyl group substituted by 1 or 2 carboxy groups,
6) a 3- to 14-membered nonaromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from a C 1-6 alkyl group substituted by 1 or 2 carboxy groups; and a carboxy group,
7) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a mono- or di-C 1-6 alkyl-carbamoyl group substituted by 1 to 3 substituents selected from a carboxy group, a hydroxy-phenyl group, and a carbamoyl group; a C 1-6 alkoxy-carbonyl group; and a carboxy group,
8) a C 1-6 alkoxy group optionally substituted by a mono- or di-C 1-6 alkyl-carbamoyl group substituted by 1 or 2 carboxy groups,
9) a mono- or di-C 1-6 alkyl-carbamoyl group optionally substituted by 1 to 3 substituents selected from
(a) a carboxy group;
(b) a sulfo group;
(c) a hydroxy group;
(d) a C 1-6 alkoxy group optionally substituted by a phenyl group;
(e) a C 1-6 alkoxy-carbonyl group;
(f) a guanidino group;
(g) a C 6-14 aryl group optionally substituted by 1 to 3 substituents selected from
 (g-1) a hydroxy group,
 (g-2) a carboxy group,
 (g-3) a C 1-6 alkoxy group,
 (g-4) a C 1-6 alkyl group substituted by a carboxy group,
 (g-5) a C 1-6 alkyl group substituted by a mono- or di-C 1-6 alkyl-amino group substituted by 1 or 2 carboxy groups, and
 (g-6) a mono- or di-C 1-6 alkyl-amino-C 1-6 alkoxy group substituted by 1 or 2 substituents selected from a carboxy group and a phenyl group;
(h) a thienyl group optionally substituted by 1 or 2 carboxy groups;
(i) a pyridinyl group optionally substituted by a mono- or di-C 1-6 alkyl-amino-C 1-6 alkyl group substituted by 1 or 2 carboxy groups;
(j) a C 1-6 alkyl-amino group substituted by 1 or 2 carboxy groups;
(k) a carbamoyl group optionally substituted by 1 or 2 C 1-6 alkyl groups substituted by 1 or 2 substituents selected from a carboxy group and a carboxy-phenyl group; and
(l) a phosphono group; and

10) a C 3-10 cycloalkyl group,

(2) 2,3-dihydrobenzofuran optionally substituted by 1 to 3 substituents selected from
1) a mono- or di-C 1-6 alkyl-carbamoyl group optionally substituted by 1 to 3 substituents selected from a carboxy group and a sulfo group, and
2) a C 1-6 alkyl group optionally substituted by a mono- or di-C 1-6 alkyl-carbamoyl group substituted by 1 to 3 substituents selected from a carboxy group and a sulfo group,
(3) pyridine optionally substituted by C 1-6 alkyl optionally substituted by a mono- or di-C 1-6 alkyl-carbamoyl group substituted by 1 or 2 carboxy groups, or
(4) thiophene optionally substituted by a mono- or di-C 1-6 alkyl-carbamoyl group optionally substituted by 1 or 2 carboxy groups.

3. The compound according to claim 1 or a salt thereof, wherein L is propylene.

4. The compound according to claim 1 or a salt thereof, wherein X 1 is a bond, and X 2 is —O—.

5. The compound according to claim 1 or a salt thereof, wherein R is a guanidino group.

6. The compound according to claim 1 or a salt thereof, wherein Y 1 is a bond, and Y 2 is —O—.

7. The compound according to claim 1 or a salt thereof, wherein
ring A is
(1) a benzene ring optionally substituted by 1 to 3 substituents selected from
1) a halogen atom,
2) a carboxy group,
3) a cyano group,
4) a carbamoyl group optionally substituted by a C 6-14 aryl group optionally substituted by 1 to 3 substituents selected from a sulfo group; and a C 1-6 alkyl group optionally substituted by a mono- or di-C 1-6 alkylphosphono group,
5) 3- to 14-membered nonaromatic heterocyclylcarbonyl optionally substituted by 1 to 3 substituents selected from a carboxy group; and a mono- or di-C 1-6 alkyl-carbamoyl group substituted by 1 or 2 carboxy groups,
6) a 3- to 14-membered nonaromatic heterocyclic group optionally substituted by 1 to 3 substituents selected from a C 1-6 alkyl group substituted by 1 or 2 carboxy groups; and a carboxy group,
7) a C 1-6 alkyl group optionally substituted by 1 to 3 substituents selected from a mono- or di-C 1-6 alkyl-carbamoyl group substituted by 1 to 3 substituents selected from a carboxy group, a hydroxy-phenyl group, and a carbamoyl group; a C 1-6 alkoxy-carbonyl group; and a carboxy group,
8) a C 1-6 alkoxy group optionally substituted by a mono- or di-C 1-6 alkyl-carbamoyl group substituted by 1 or 2 carboxy groups,
9) a mono- or di-C 1-6 alkyl-carbamoyl group optionally substituted by 1 to 3 substituents selected from
(a) a carboxy group;
(b) a sulfo group;
(c) a hydroxy group;
(d) a C 1-6 alkoxy group optionally substituted by a phenyl group;
(e) a C 1-6 alkoxy-carbonyl group;
(f) a guanidino group;
(g) a C 6-14 aryl group optionally substituted by 1 to 3 substituents selected from
 (g-1) a hydroxy group,
 (g-2) a carboxy group,
 (g-3) a C 1-6 alkoxy group,
 (g-4) a C 1-6 alkyl group substituted by a carboxy group,
 (g-5) a C 1-6 alkyl group substituted by a mono- or di-C 1-6 alkyl-amino group substituted by 1 or 2 carboxy groups, and
 (g-6) a mono- or di-C 1-6 alkyl-amino-C 1-6 alkoxy group substituted by 1 or 2 substituents selected from a carboxy group and a phenyl group;
(h) a thienyl group optionally substituted by 1 or 2 carboxy group;
(i) a pyridinyl group optionally substituted by a mono- or di-C 1-6 alkyl-amino-C 1-6 alkyl group substituted by 1 or 2 carboxy groups;
(j) a C 1-6 alkyl-amino group substituted by 1 or 2 carboxy groups;
(k) a carbamoyl group optionally substituted by 1 or 2 C 1-6 alkyl groups substituted by 1 or 2 substituents selected from a carboxy group and a carboxy-phenyl group; and
(l) a phosphono group; and

10) a C 3-10 cycloalkyl group,

(2) 2,3-dihydrobenzofuran optionally substituted by 1 to 3 substituents selected from
1) a mono- or di-C 1-6 alkyl-carbamoyl group optionally substituted by 1 to 3 substituents selected from a carboxy group and a sulfo group, and
2) a C 1-6 alkyl group optionally substituted by a mono- or di-C 1-6 alkyl-carbamoyl group substituted by 1 to 3 substituents selected from a carboxy group and a sulfo group,
(3) pyridine optionally substituted by C 1-6 alkyl optionally substituted by a mono- or di-C 1-6 alkyl-carbamoyl group substituted by 1 or 2 carboxy groups, or
(4) thiophene optionally substituted by a mono- or di-C 1-6 alkyl-carbamoyl group optionally subs

Assignees

• Takeda Pharmaceuticals Co

Inventors

• Sasaki Minoru
• Kikuchi Fumiaki
• Ikeda Zenichi
• Kakegawa Keiko
• Nishikawa Yoichi
• Sasaki Shigekazu
• Fukuda Koichiro
• Takami Kazuaki
• Banno Yoshihiro
• Kamaura Masahiro

Classifications

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/04

  Anorexiants; Antiobesity agents · CPC title

• A61K31/662

  Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon · CPC title

• C07D491/044

  with only one oxygen atom as ring hetero atom in the oxygen-containing ring · CPC title