Benzazepine derivatives

Abstract

The present invention relates to benzazepine derivatives. The present invention provides, inter alia, a benzazepine compound of formula (1) or a salt thereof having vasopressin V1a and V2 antagonism and advantageous metabolic stability and absorption characteristics, and a medical use thereof. In the formula, R1 is an optionally substituted C1-6 alkyl group or the like; l is-C (= O)-NH-or the like; ring A1 is a hydrocarbon ring or the like; ring A2 is a hydrocarbon ring or the like; and each of rings A1 and A2 may have at least one substituent. # imgabs0 #

Claims

1. A benzazepine compound of formula (1) or a salt thereof, [Chemical formula 1] Where R 1 is deuterium, OH, COOH, optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkyl-O-CO- or optionally substituted C 2-6 alkenyl; L is a direct bond or -C(=O)-NH-; Ring A 1 is a hydrocarbon ring or a heterocyclic ring; Ring A 2 is a hydrocarbon ring or a heterocyclic ring; and Ring A 1 and A 2 Each of may have at least one substituent.

2. The compound or salt thereof according to claim 1, wherein ring A 1 is a saturated or unsaturated 3 to 8 membered monocyclic hydrocarbon ring, or a saturated or unsaturated 3 to 15 membered monocyclic, bicyclic or tricyclic heterocyclic ring containing 1 to 5 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring members, Ring A 2 is a saturated or unsaturated 3 to 8 membered monocyclic hydrocarbon ring, or a saturated or unsaturated 3 to 15 membered monocyclic, bicyclic or tricyclic heterocyclic ring containing 1 to 5 heteroatoms independently selected from nitrogen, oxygen and sulfur as ring members, and Ring A 1 and A 2 Each of may have at least one substituent.

3. The compound or salt thereof according to claim 1 or 2, wherein ring A 1 is a saturated or unsaturated 3- to 8-membered monocyclic hydrocarbon ring, a saturated or unsaturated 5- or 6-membered heteromonocyclic ring containing 1 to 4 nitrogen atoms as ring heteroatoms, a saturated or unsaturated 7- to 15-membered heterobicyclic ring containing 1 to 5 nitrogen atoms as ring heteroatoms, a saturated or unsaturated 5- or 6-membered heteromonocyclic ring containing 1 or 2 oxygen atoms and at least one nitrogen atom as ring heteroatoms, or a saturated or unsaturated 5- or 6-membered heteromonocyclic ring containing 1 or 2 sulfur atoms and at least one nitrogen atom as ring heteroatoms, Ring A 2 is a saturated or unsaturated 3- to 8-membered monocyclic hydrocarbon ring, a saturated or unsaturated 5- or 6-membered heteromonocyclic ring containing 1 to 4 nitrogen atoms as ring heteroatoms, a saturated or unsaturated 5- or 6-membered heteromonocyclic ring containing 1 or 2 oxygen atoms as ring heteroatoms, a saturated or unsaturated 7- to 12-membered heterobicyclic ring containing 1 to 3 oxygen atoms as ring heteroatoms, a saturated or unsaturated 5- or 6-membered heteromonocyclic ring containing 1 or 2 sulfur atoms as ring heteroatoms, a saturated or unsaturated 7- to 15-membered heterobicyclic ring containing 1 to 5 nitrogen atoms as ring heteroatoms, a saturated or unsaturated 5- or 6-membered heteromonocyclic ring containing 1 or 2 oxygen atoms and at least one nitrogen atom as ring heteroatoms, or a saturated or unsaturated 5- or 6-membered heteromonocyclic ring containing 1 or 2 sulfur atoms and at least one nitrogen atom as ring heteroatoms, and Ring A 1 and A 2 Each of may have at least one substituent.

4. The compound or salt thereof according to any one of claims 1 to 3, wherein ring A 1 is benzene, pyridine, pyrazine or tetrahydroisoquinoline, and Ring A 1 may have 1 to 4 substituents independently selected from the following: optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 alkyl-O-, halogen, and oxo; Ring A 2 is benzene, pyridine, furan, thiophene or tetrahydroisoquinoline, and Ring A 2 may have 1 to 4 substituents independently selected from the following: optionally substituted C 1-6 Alkyl, optionally substituted C 1-6 Alkyl-O-, optionally substituted C 3-6 cycloalkyl, halogen, oxo, optionally substituted phenyl and optionally substituted pyridyl, The condition is that when ring A 2 When there are multiple substituents on the carbon atom of the ring, the substituents can be combined with the carbon atom to form a C 3-6 Cycloalkyl.

5. The compound or salt thereof according to claim 4, wherein in ring A 1 wherein the optionally substituted C 1-6 Alkyl or optionally substituted C 1-6 The substituents of alkyl-O- are each independently the same or different and are 1 to 3 groups selected from the following: halogen and C 1-6 Alkyl-O-, In Ring A 2 wherein the optionally substituted C 1-6 Alkyl or optionally substituted C 1-6 The substituents of alkyl-O- are each independently the same or different 1 to 3 halogens, the optionally substituted C 3-6 The substituents of the cycloalkyl group are the same or different 1 to 3 halogens, and the substituents of the optionally substituted phenyl group are 1 to 3 groups independently selected from the following groups: halogen, C 1-6 Alkyl and C 1-6 The substituents of the optionally substituted pyridyl are the same or different 1 to 3 halogens.

6. The compound or salt thereof according to any one of claims 1 to 5, wherein R 1 is deuterium; OH; COOH; C optionally substituted by 1 to 3 groups independently selected from 1-6 Alkyl: optionally substituted amino, optionally substituted C 1-6 Alkyl-O-, optionally substituted C 1-6 Alkyl-SO 2 -O-, optionally substituted silyl-O-, OH, optionally substituted C 1-6 alkyl-COO-, tetrahydropyranyl-O-, thiazolyl and pyridyl; optionally substituted C 1-6 Alkyl-O-CO-; or optionally substituted C 2-6 Alkenyl, The optionally substituted amino group is an amino group optionally substituted by 1 or 2 groups independently selected from the following groups: C optionally substituted by OH 1-6 Alkyl, optionally substituted C 1-6 Alkyl-SO 2 -, optionally substituted C 1-6 Alkyl-O-CO- and benzyl-O-CO-, The optionally substituted C 1-6 Alkyl-O-, optionally substituted C 1-6 Alkyl-SO 2 -, optionally substituted C 1-6 Alkyl-SO 2 -O-, optionally substituted C 1-6 Alkyl-COO- and optionally substituted C 1-6 The optionally substituted C 1-6 Alkyl is a C optionally substituted by 1 to 3 groups independently selected from 1-6 Alkyl: halogen, C 1-6 Alkyl-O-, optionally substituted phenyl, optionally substituted phenyl-SO 2 -NH- and naphthyl-SO 2 -NH-, the optionally substituted phenyl is phenyl optionally substituted by 1 to 3 groups independently selected from the following: halogen, C 1-6 Alkyl and NO 2 , The optionally substituted silyl-O- is optionally substituted with the same or different 1 to 3 C 1-6 alkyl-substituted silyl-O-, and The optionally substituted C 2-6 Alkenyl is a C 2-6 Alkenyl.

7. A compound or a salt thereof according to any one of claims 1 to 6, wherein R 1 is deuterium; OH; or C optionally substituted by 1-6 Alkyl: optionally substituted amino, optionally substituted C 1-6 Alkyl-O- or OH, The optionally substituted amino group is an amino group optionally substituted by: C 1-6 Alkyl, and The optionally substituted C 1-6 Alkyl-O- is a C 1-6 Alkyl-O-.

8. A compound or a salt thereof according to any one of claims 1 to 7, wherein R 1 is C replaced by OH 1-6 alkyl.

9. The compound or salt thereof according to any one of claims 1 to 8, wherein ring A 1 is benzene optionally substituted by halogen, C 1-6 Alkyl, halo-C 1-6 Alkyl, C 1-6 Alkyl-O-, halo-C 1-6 Alkyl-O-, C 1-6 Alkyl-OC 1-6 Alkyl-O-, halo-C 1-6 Alkyl-OC 1-6 Alkyl-O-, C 1-6 Alkyl-O-halo-C 1-6 Alkyl-O- or halo-C 1-6 Alkyl-O-halo-C 1-6 alkyl-O-; pyridine optionally substituted by halogen; pyrazine; or tetrahydroisoquinoline optionally substituted by oxo; and Ring A 2 is benzene optionally substituted by 1 to 3 groups independently selected from the group consisting of halogen, C 1-6 Alkyl, halo-C 1-6 Alkyl, C 1-6 Alkyl-O-, halo-C 1-6 Alkyl-O-, C 3-6 Cycloalkyl, optionally substituted phenyl and pyridyl, wherein the optionally substituted phenyl is phenyl optionally substituted by halogen, C 1-6 Alkyl, halo-C 1-6 Alkyl, C 1-6 Alkyl-O- or halo-C 1-6 Alkyl-O-; pyridine optionally substituted by: C 1-6 Alkyl, halo-C 1-6 Alkyl or phenyl; optionally C 1-6 Alkyl-substituted furan; optionally C 1-6 alkyl-substituted thiophene; or tetrahydroisoquinoline optionally substituted by 1 to 3 groups independently selected from the following: halogen, C 1-6 alkyl and oxo, provided that when tetrahydroisoquinoline has multiple C 1-6 When alkyl, the C 1-6 Alkyl groups can be combined with the carbon atoms to form C 3-6 Cycloalkyl.

10. A compound or a salt thereof according to any one of claims 1 to 9, wherein R 1 is C replaced by OH 1-6 alkyl, Ring A 1 is benzene optionally substituted by halogen, C 1-6 Alkyl, C 1-6 Alkyl-O- or C 1-6 Alkyl-OC 1-6 alkyl-O-; or pyridine optionally substituted by halogen, and Ring A 2 is benzene optionally substituted by 1 to 3 groups independently selected from the group consisting of halogen, C 1-6 Alkyl, halo-C 1-6 Alkyl, C 1-6 Alkyl-O-, halo-C 1-6 Alkyl-O-, C 3-6 Cycloalkyl, optionally substituted phenyl and pyridyl, wherein the optionally substituted phenyl is phenyl optionally substituted by halogen, C 1-6 Alkyl, halo-C 1-6 Alkyl, C 1-6 Alkyl-O- or halo-C 1-6 Alkyl-O-.

11. A compound or a salt thereof according to any one of claims 1 to 9, wherein R 1 is C replaced by OH 1-6 alkyl, Ring A 1 is benzene optionally substituted by halogen, C 1-6 Alkyl-O- or halo-C 1-6 alkyl-O-; or pyridine, and Ring A 2 is benzene optionally substituted by 1 to 3 groups independently selected from the group consisting of halogen, C 1-6 Alkyl, halo-C 1-6 Alkyl and phenyl optionally substituted by halogen; optionally phenyl or halo-C 1-6 alkyl-substituted pyridine; or tetrahydroisoquinoline optionally substituted by 1 to 3 groups independently selected from halogen and oxo. 12 . The compound or salt thereof according to claim 1 , wherein L is —C(═O)—NH—.

13. A compound or a salt thereof, wherein the compound is selected from the following group of compounds: [Chemical formula 2-1] [Chemical formula 2-2] [Chemical formula 2-3] 。

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