# US 10,501,440 B2 · Heteroarylcarboxamide derivatives as plasma kallikrein inhibitors

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- Number: US 10,501,440 B2
- Document ID: US10501440B2
- Status: Granted
- Kind: B2
- Application number: 15/953,523
- Filed: 2018-04-16
- Published: 2018-10-25
- Granted: 2019-12-10
- Earliest claimed: 2017-04-21
- Assignees: Boehringer Ingelheim International GmbH
- Applicants: Boehringer Ingelheim International GmbH
- Inventors: Sara Frattini; Iain Lingard; Dieter Wolfgang Hamprecht; Remko Alexander Bakker; Matthias Eckhardt; Andreas Gollner; Joerg P. Hehn; Elke Langkopf; Holger Wagner; Bernd Wellenzohn; Dieter Wiedenmayer
- Web page: https://patentgrep.com/patent/US10501440B2

## CPC

- C07D 401/14: containing three or more hetero rings
- A61K 31/444: containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
- A61K 31/506: not condensed and containing further heterocyclic rings
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

Disclosed are heteroarylcarboxamides of formula (I), and pharmaceutically acceptable salts thereof, wherein A, T, R1, R2 and R3 are as defined herein. Also disclosed are methods of using these compounds for the treatment of diseases which can be influenced by inhibition of plasma kallikrein.

## Claims

### Claim 1

A compound of formula (I)
wherein
A is selected from the group A-G1 consisting of N and CH;
T is selected from the group T-G1 consisting of N, C—H, C—C1-4-alkyl, C—CHF2, C—CF3 and C—OCH3;
R1 is selected from the group R1-G1 consisting of C1-3-alkyl;
R2 is selected from the group R2-G1 consisting of a fused or spiro bicyclic ring system consisting of 1 N atom and 5 to 6 C atoms as ring members, wherein the ring system is attached via the N atom to the monocyclic heteroaromatic ring in formula (I) and wherein the ring system is optionally substituted with one substituent selected from the group consisting of F, C1-3-alkyl, CF3, CN, HO—C1-3-alkyl- and C1-3-alkyloxy- and wherein the ring system is optionally additionally substituted with one substituent selected from the group consisting of F and CH3; and
R3 is selected from the group R3-G1 consisting of H, CH3, CHF2 or CF3,
or a salt thereof.

### Claim 2 (depends on 1)

The compound according to claim 1, wherein
A is CH,
or a salt thereof.

### Claim 3 (depends on 1)

The compound according to claim 1, wherein
A is N,
or a salt thereof.

### Claim 4 (depends on 1)

The compound according to claim 1, wherein
T is selected from the group T-G3 consisting of N, C—H, C—CH3, C—CH(CH3)2, C—CHF2, C—CF3 and C—OCH3,
or a salt thereof.

### Claim 5 (depends on 1)

The compound according to claim 1, wherein
R1 is CH3,
or a salt thereof.

### Claim 6 (depends on 1)

The compound according to claim 1, wherein
R2 is selected from the group R2-G4 consisting of
wherein, as indicated by the asterisk, the ring system is attached via the N atom to the monocyclic heteroaromatic ring in formula (I),
or a salt thereof.

### Claim 7 (depends on 1)

The compound according to claim 1, wherein
R3 is selected from the group R3-G2 consisting of H and CH3,
or a salt thereof.

### Claim 8 (depends on 1)

The compound according to claim 1, wherein the compound of formula (I) is selected from the group consisting of
or a salt thereof.

### Claim 9 (depends on 1)

A pharmaceutically acceptable salt of a compound according to claim 1.

### Claim 10 (depends on 1)

A pharmaceutical composition comprising one or more compounds according to claim 1, or pharmaceutically acceptable salts thereof, optionally together with one or more inert carriers and/or diluents.

### Claim 11 (depends on 1)

A pharmaceutical composition comprising one or more compounds according to claim 1, or pharmaceutically acceptable salts thereof, and one or more additional therapeutic agents, optionally together with one or more inert carriers and/or diluents.

### Claim 12 (depends on 11)

The pharmaceutical composition according to claim 11 wherein the one or more additional therapeutic agents are selected from the group consisting of antidiabetic agents, agents for the treatment of overweight and/or obesity, agents for the treatment of high blood pressure, heart failure and/or atherosclerosis and agents for the treatment of ocular diseases.

### Claim 13 (depends on 1)

A method for treatment of diabetic complications, in a patient in need thereof, the method comprising administering a compound according to claim 1, or pharmaceutically acceptable salts thereof, to the patient.

### Claim 14 (depends on 13)

The method according to claim 13, wherein the diabetic complication is retinal vascular permeability associated with diabetic retinopathy or diabetic macular edema.