# US 9,751,858 B2 · 3-heteroaroylamino-propionic acid derivatives and their use as pharmaceuticals

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 9,751,858 B2
- Document ID: US9751858B2
- Status: Granted
- Kind: B2
- Application number: 15/140,350
- Filed: 2016-04-27
- Published: 2016-08-18
- Granted: 2017-09-05
- Earliest claimed: 2011-07-26
- Assignees: Sanofi
- Applicants: Sanofi
- Inventors: Sven Ruf; Josef Pernerstorfer; Thorsten Sadowski; Georg Horstick; Herman Schreuder; Christian Buning; Klaus Wirth
- Web page: https://patentgrep.com/patent/US9751858B2

## CPC

- C07D 401/06: linked by a carbon chain containing only aliphatic carbon atoms
- A61K 31/341: not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
- A61K 31/415: 1,2-Diazoles
- A61K 31/4164: 1,3-Diazoles
- A61K 31/4196: 1,2,4-Triazoles
- A61K 31/42: Oxazoles
- A61K 31/421: 1,3-Oxazoles, e.g. pemoline, trimethadione
- A61K 31/4245: Oxadiazoles
- A61K 31/426: 1,3-Thiazoles
- A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/02: Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
- A61P 7/06: Antianaemics
- A61P 7/08: Plasma substitutes; Perfusion solutions; Dialytics or haemodialytics; Drugs for electrolytic or acid-base disorders, e.g. hypovolemic shock (artificial tears A61P27/04)
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 7/12: Antidiuretics, e.g. drugs for diabetes insipidus (ADH A61P5/10)
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/04: Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
- A61P 9/08: Vasodilators for multiple indications
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/12: Antihypertensives
- A61P 11/00: Drugs for disorders of the respiratory system
- A61P 11/06: Antiasthmatics
- A61P 13/00: Drugs for disorders of the urinary system
- A61P 13/12: of the kidneys
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- A61P 19/04: for non-specific disorders of the connective tissue
- A61P 25/00: Drugs for disorders of the nervous system
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 37/02: Immunomodulators
- C07D 231/14: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D 233/90: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D 249/10: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D 261/18: Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
- C07D 263/34: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D 271/06: 1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
- C07D 271/10: 1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D 277/32: with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D 277/56: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C07D 285/08: 1,2,4-Thiadiazoles; Hydrogenated 1,2,4-thiadiazoles
- C07D 307/68: Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- 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

The present invention relates to compounds of the formula I, wherein Ht, G, R10, R30, R40, R50 and R60 have the meanings indicated in the claims, which are valuable pharmaceutical active compounds. They are inhibitors of the protease cathepsin A, and are useful for the treatment of diseases such as atherosclerosis, heart failure, renal diseases, liver diseases or inflammatory diseases, for example. The invention furthermore relates to processes for the preparation of the compounds of the formula I, their use and pharmaceutical compositions comprising them.

## Claims

### Claim 1

A compound selected from the group consisting of:
3-Cyclohexyl-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
3-[(5-Methyl-2-phenyl-oxazole-4-carbonyl)-amino]-4-phenyl-butyric acid;
(S)-3-[(5-Methyl-2-phenyl-oxazole-4-carbonyl)-amino]-3-o-tolyl-propionic acid;
(S)-3-(2-Fluoro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(3-Fluoro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(4-Fluoro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-phenyl-propionic acid;
(R)-3-{[3-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-5-carbonyl]-amino}-4-phenyl-butyric acid;
(S)-3-{[5-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid;
(R)-3-{[5-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-4-phenyl-butyric acid;
(S)-3-{[5-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-phenyl-butyric acid;
(S)-3-{[5-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid;
(S)-3-{[5-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid;
(S)-3-(2-Fluoro-phenyl)-3-{[5-(2-fluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-propionic acid;
(S)-3-(3-Fluoro-phenyl)-3-{[5-(2-fluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-propionic acid;
(S)-3-(4-Fluoro-phenyl)-3-{[5-(2-fluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-propionic acid;
(S)-3-{[5-(2,3-Difluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-phenyl-propionic acid;
(S)-3-[(1-Ethyl-5-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-o-tolyl-propionic acid;
(S)-3-[(5-Isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-3-phenyl-propionic acid;
(S)-3-(4-Methoxy-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(3-Methoxy-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-o-tolyl-propionic acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-m-tolyl-propionic acid;
(S)-3-(3-Chloro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(R)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-4-phenyl-butyric acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-phenyl-butyric acid;
(S)-3-{3-[3-(2-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-3-phenyl-propionic acid;
(S)-3-(2-Chloro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
3-Cyclohexyl-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2-Fluoro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
(S)-3-(3-Fluoro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
(S)-3-(4-Fluoro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
(S)-3-{[5-(2,3-Difluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid;
(S)-3-{[5-(2,3-Difluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid;
(S)-3-{[5-(2,3-Difluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-phenyl-butyric acid;
(R)-3-{[5-(2,3-Difluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-4-phenyl-butyric acid;
(S)-3-{[5-(2,3-Difluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid;
(S)-3-{[5-(2,3-Difluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-(2-fluoro-phenyl)-propionic acid;
(S)-3-{[5-(2,3-Difluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-(4-fluoro-phenyl)-propionic acid;
3-[(5-Isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-4-phenyl-butyric acid;
(S)-3-[(5-Dimethylsulfamoyl-2-methyl-furan-3-carbonyl)-amino]-3-o-tolyl-propionic acid;
(S)-3-(2-Fluoro-phenyl)-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(4-Fluoro-phenyl)-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(R)-3-{3-[3-(2-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-4-phenyl-butyric acid;
(S)-3-{3-[3-(2-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-3-m-tolyl-propionic acid;
(S)-3-{3-[3-(2-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-3-phenyl-butyric acid;
(S)-3-{3-[3-(2-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-3-p-tolyl-propionic acid;
(S)-3-{3-[3-(2-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-3-o-tolyl-propionic acid;
(S)-3-(4-Fluoro-phenyl)-3-{3-[3-(2-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-propionic acid;
(S)-3-(2-Fluoro-phenyl)-3-{3-[3-(2-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-propionic acid;
(S)-3-(3-Fluoro-phenyl)-3-{3-[3-(2-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-propionic acid;
(S)-3-(3-Chloro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
3-(2-Chloro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
(S)-3-(4-Chloro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
(S)-3-{[1-Methyl-4-(propane-1-sulfonylamino)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid;
(S)-3-[(5-Isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-3-(3-methoxy-phenyl)-propionic acid;
(S)-3-(2,3-Dimethoxy-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2-Chloro-phenyl)-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
3-Cyclohexyl-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-{3-[3-(2-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-3-(4-methoxy-phenyl)-propionic acid;
(S)-3-(3-Chloro-phenyl)-3-{3-[3-(2-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-propionic acid;
(S)-3-(2,4-Dichloro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2,3-Dichloro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-3-o-tolyl-propionic acid;
(S)-3-[(5-Methyl-2-phenyl-oxazole-4-carbonyl)-amino]-3-(2-trifluoromethyl-phenyl)-propionic acid;
(S)-3-(3-Fluoro-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-{[5-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic acid;
(S)-3-{[5-(2-Fluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-(3-trifluoromethyl-phenyl)-propionic acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-(3-trifluoromethyl-phenyl)-propionic acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-(4-trifluoromethyl-phenyl)-propionic acid;
(S)-3-(2,3-Dichloro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
(S)-3-{[4-(2,2-Dimethyl-propane-1-sulfonylamino)-1-methyl-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid;
(S)-3-(3-Chloro-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2-Chloro-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-[(1-Benzyl-5-phenyl-1H-pyrazole-3-carbonyl)-amino]-3-o-tolyl-propionic acid;
(S)-3-(4-Chloro-phenyl)-2-{[5-(4-trifluoromethyl-pyridin-3-yl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-propionic acid;
(S)-3-{[1-Ethyl-5-(2-propyl-piperidine-1-carbonyl)-1H-pyrazole-3-carbonyl]-amino}-3-phenyl-propionic acid;
(S)-3-{[5-(2,3-Difluoro-phenyl)-[1,2,4]oxadiazole-3-carbonyl]-amino}-3-(2-trifluoromethyl-phenyl)-propionic acid;
(S)-3-(2,3-Dichloro-phenyl)-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2,4-Dichloro-phenyl)-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-[(4-Cyclohexylmethanesulfonylamino-1-methyl-1H-pyrazole-3-carbonyl)-amino]-3-phenyl-propionic acid;
(S)-3-{3-[3-(2-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-3-(2-trifluoromethyl-phenyl)-propionic acid;
(S)-3-{3-[3-(2-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-3-(4-trifluoromethyl-phenyl)-propionic acid;
(S)-3-(2,3-Dichloro-phenyl)-3-{3-[3-(2-fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-propionic acid;
(S)-3-{3-[3-(2-Fluoro-phenyl)-[1,2,4]oxadiazol-5-yl]-propionylamino}-3-(3-trifluoromethyl-phenyl)-propionic acid;
(S)-3-{[1-Ethyl-5-(2-propyl-piperidine-1-carbonyl)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid;
(S)-3-{[1-Ethyl-5-(2-propyl-piperidine-1-carbonyl)-1H-pyrazole-3-carbonyl]-amino}-3-p-tolyl-propionic acid;
(S)-3-{[1-Ethyl-5-(2-propyl-piperidine-1-carbonyl)-1H-pyrazole-3-carbonyl]-amino}-3-m-tolyl-propionic acid;
(S)-3-[(1-Methyl-4-phenylmethanesulfonylamino-1H-pyrazole-3-carbonyl)-amino]-3-o-tolyl-propionic acid;
(S)-3-{[1-(4-Fluoro-benzyl)-5-phenyl-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid;
(S)-3-[(4-Cyclohexylmethanesulfonylamino-1-methyl-1H-pyrazole-3-carbonyl)-amino]-3-o-tolyl-propionic acid;
(S)-3-(2,3-Dimethoxy-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-{[1-Methyl-4-(2-phenyl-ethanesulfonylamino)-1H-pyrazole-3-carbonyl]-amino}-3-o-tolyl-propionic acid;
(S)-3-(2,3-Dichloro-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid; and
(S)-3-(2,4-Dichloro-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid,
in any stereoisomeric forms thereof, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate thereof.

### Claim 2

A compound of formula I, in any of its stereoisomeric forms or a physiologically acceptable salt thereof, or a physiologically acceptable solvate thereof,
wherein:
Ht is
G is R71—O—C(O)—;
R1 is selected from the group consisting of hydrogen, halogen, (C1-C6)-alkyl, CF3, (C3-C7)-cycloalkyl-CsH2s—, Ar—CsH2s—, Ar—O, (C1-C6)-alkyl-O—, (C1-C6)-alkyl-S(O)m— and NC—; wherein s is independently 0, 1, 2 or 3;
R2 is selected from the group consisting of hydrogen, halogen, (C1-C6)-alkyl, CF3, (C1-C6)-alkyl-O—, (C1-C6)-alkyl-S(O)m— and NC—;
R10 is Ar;
R30 is selected from the group consisting of (C3-C7)-cycloalkyl and R32—CuH2u—, wherein u is independently 0, 1, 2 or 3;
R32 is selected from the group consisting of phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle containing one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and bonded via a ring carbon atom,
wherein the phenyl and the heterocycle are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, HO—, (C1-C6)-alkyl-O—, —O—CH2—O—, —O—CF2—O—, (C1-C6)-alkyl-S(O)m—, H2N—S(O)2—, (C1-C4)-alkyl-NH—S(O)2—, di((C1-C4)-alkyl)N—S(O)2—, H2N—, (C1-C6)-alkyl-NH—, di((C1-C6)-alkyl)N—, (C1-C4)-alkyl-C(O)—NH—, (C1-C4)-alkyl-S(O)2—NH— and NC—;
R40 is hydrogen or (C1-C4)-alkyl;
R50 is selected from the group consisting of hydrogen, (C1-C6)-alkyl, HO— and (C1-C6)-alkyl-O—;
R60 is hydrogen or (C1-C6)-alkyl;
R71 is hydrogen;
Ar, independently of each other group Ar, is selected from the group consisting of phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle containing one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and bonded via a ring carbon atom, wherein the phenyl and the heterocycle are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, (C1-C6)-alkyl-O—, —O—CH2—O—, O—CH2—CH2—O—, —O—CF2—O—, (C1-C6)-alkyl-S(O)m—, H2N—S(O)2—, CF3 and NC—;
m, independently of each other number m, is 0, 1 or 2;
wherein all cycloalkyl groups, independently of each other, are optionally substituted by one or more identical or different substituents selected from the group consisting of fluorine and (C1-C4)-alkyl; and
wherein all alkyl, CsH2s, and CuH2u groups, independently of each other, and independently of any other substituents, are optionally substituted by one or more fluorine substituents.

### Claim 3 (depends on 2)

The compound of claim 2, in any of its stereoisomeric forms or a physiologically acceptable salt thereof, or a physiologically acceptable solvate thereof, wherein the compound of formula I is a compound of formula I-2:
wherein R2 is selected from the group consisting of hydrogen, halogen, (C1-C6)-alkyl, CF3, (C1-C6)-alkyl-O—, and NC—.

### Claim 4 (depends on 2)

The compound of claim 2, in any of its stereoisomeric forms or a physiologically acceptable salt thereof, or a physiologically acceptable solvate thereof, wherein:
R30 is R32—CuH2u—, wherein u is independently 0 or 1;
R32 is selected from the group consisting of phenyl and an aromatic 5-membered or 6-membered monocyclic heterocycle containing one, two or three identical or different ring heteroatoms selected from the group consisting of nitrogen, oxygen and sulfur and bonded via a ring carbon atom, and wherein the phenyl and the heterocycle are optionally substituted by one or more identical or different substituents selected from the group consisting of halogen, (C1-C6)-alkyl, (C3-C7)-cycloalkyl, HO—, (C1-C6)-alkyl-O—, —O—CH2—O—, —O—CF2—O—, (C1-C6)-alkyl-S(O)m—, H2N—S(O)2—, (C1-C4)-alkyl-NH—S(O)2—, di((C1-C4)-alkyl)N—S(O)2—, H2N—, (C1-C6)-alkyl-NH—, di((C1-C6)-alkyl)N—, (C1-C4)-alkyl-C(O)—NH—, (C1-C4)-alkyl-S(O)2—NH— and NC—; and
R40 is hydrogen.

### Claim 5 (depends on 2)

The compound of claim 2, in any of its stereoisomeric forms or a physiologically acceptable salt thereof, or a physiologically acceptable solvate thereof, wherein:
R50 is hydrogen; and
R60 is hydrogen.

### Claim 6 (depends on 2)

The compound of claim 2, in any of its stereoisomeric forms or a physiologically acceptable salt thereof, or a physiologically acceptable solvate thereof, wherein:
R30 is R32—CuH2u—, wherein u is independently 0 or 1; and
R40 is hydrogen.

### Claim 7

A compound selected from the group consisting of:
3-Cyclohexyl-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
3-[(5-Methyl-2-phenyl-oxazole-4-carbonyl)-amino]-4-phenyl-butyric acid;
(S)-3-[(5-Methyl-2-phenyl-oxazole-4-carbonyl)-amino]-3-o-tolyl-propionic acid;
(S)-3-(2-Fluoro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(3-Fluoro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(4-Fluoro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-phenyl-propionic acid;
(S)-3-[(5-Isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-3-phenyl-propionic acid;
(S)-3-(4-Methoxy-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(3-Methoxy-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-o-tolyl-propionic acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-m-tolyl-propionic acid;
(S)-3-(3-Chloro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(R)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-4-phenyl-butyric acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-phenyl-butyric acid;
(S)-3-(2-Chloro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
3-Cyclohexyl-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2-Fluoro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
(S)-3-(3-Fluoro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
(S)-3-(4-Fluoro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
3-[(5-Isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-4-phenyl-butyric acid;
(S)-3-(2-Fluoro-phenyl)-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(4-Fluoro-phenyl)-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(3-Chloro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
3-(2-Chloro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
(S)-3-(4-Chloro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
(S)-3-[(5-Isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-3-(3-methoxy-phenyl)-propionic acid;
(S)-3-(2,3-Dimethoxy-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2-Chloro-phenyl)-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
3-Cyclohexyl-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2,4-Dichloro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2,3-Dichloro-phenyl)-3-[(5-methyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-[(2-Phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-3-o-tolyl-propionic acid;
(S)-3-[(5-Methyl-2-phenyl-oxazole-4-carbonyl)-amino]-3-(2-trifluoromethyl-phenyl)-propionic acid;
(S)-3-(3-Fluoro-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-(3-trifluoromethyl-phenyl)-propionic acid;
(S)-3-{[2-(2-Fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-3-(4-trifluoromethyl-phenyl)-propionic acid;
(S)-3-(2,3-Dichloro-phenyl)-3-{[2-(2-fluoro-phenyl)-5-methyl-oxazole-4-carbonyl]-amino}-propionic acid;
(S)-3-(3-Chloro-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2-Chloro-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2,3-Dichloro-phenyl)-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2,4-Dichloro-phenyl)-3-[(5-isopropyl-2-phenyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2,3-Dimethoxy-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid;
(S)-3-(2,3-Dichloro-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid; and
(S)-3-(2,4-Dichloro-phenyl)-3-[(2-phenyl-5-trifluoromethyl-oxazole-4-carbonyl)-amino]-propionic acid,
in any of its stereoisomeric forms or a physiologically acceptable salt thereof, or a physiologically acceptable solvate thereof.

### Claim 8 (depends on 1)

A pharmaceutical composition, comprising:
the compound of claim 1, in any of its stereoisomeric forms, or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate thereof; and
a pharmaceutically acceptable carrier.

### Claim 9 (depends on 2)

A pharmaceutical composition, comprising:
the compound of claim 2, in any of its stereoisomeric forms, or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate thereof; and
a pharmaceutically acceptable carrier.

### Claim 10 (depends on 7)

A pharmaceutical composition, comprising:
the compound of claim 7, in any of its stereoisomeric forms, or a mixture of stereoisomeric forms in any ratio, or a physiologically acceptable salt thereof, or a physiologically acceptable solvate thereof; and
a pharmaceutically acceptable carrier.

### Claim 11 (depends on 8)

A method of treating heart failure, congestive heart failure, cardiomyopathy, myocardial infarction, left ventricular dysfunction, cardiac hypertrophy, valvular heart diseases, hypertension, atherosclerosis, peripheral arterial occlusive disease, restenosis, vascular permeability disorders, treatment of edema, thrombosis, rheumatoid arthritis, osteoarthritis, renal failure, cystic fibrosis, chronic bronchitis, chronic obstructive pulmonary disease, asthma, immunological diseases, diabetic complications, fibrotic diseases, pain, ischemia or reperfusion damage, neurodegenerative diseases, or for cardioprotection or renoprotection, or as a diuretic in a patient in need thereof comprising administering to said patient a therapeutically effective amount of the pharmaceutical composition of claim 8.

### Claim 12 (depends on 2)

A process for the preparation of a compound of claim 2, or a physiologically acceptable salt thereof; or a physiologically solvate thereof, comprising reacting a compound of the formula II with a compound of the formula III,
wherein the groups Ht, G, R10, R11, R30, R40, R50 and R60 in the compounds of the formulae II and III are defined as in the compounds of the formula I and additionally functional groups can be present in protected form or in the form of a precursor group, and wherein the group J in the compound of the formula II is selected from the group consisting of HO—, (C1-C4)-alkyl-O— and halogen.