# US 2010/0168145 A1 · Fused imidazole derivatives and use thereof as aldosterone synthase inhibitors

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- Number: US 2010/0168145 A1
- Document ID: US20100168145A1
- Status: Published application
- Kind: A1
- Application number: 11/921,313
- Filed: 2006-05-30
- Published: 2010-07-01
- Earliest claimed: 2005-05-31
- Assignees: Speedel Experimenta AG
- Inventors: Peter Herold; Robert Mah; Vincenzo Tschinke; Aleksandar Stojanovic; Christiane Marti; Nathalie Jotterand; Christoph Schumacher; Michael Quirmbach
- Web page: https://patentgrep.com/patent/US20100168145A1

## CPC

- C07D 471/04: Ortho-condensed systems
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 3/04: Anorexiants; Antiobesity agents
- A61P 3/06: Antihyperlipidemics
- A61P 3/12: for electrolyte homeostasis
- A61P 5/02: of the hypothalamic hormones, e.g. TRH, GnRH, CRH, GRH, somatostatin
- A61P 5/42: for decreasing, blocking or antagonising the activity of mineralocorticosteroids
- A61P 7/10: Antioedematous agents; Diuretics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- 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 13/00: Drugs for disorders of the urinary system
- A61P 13/12: of the kidneys
- A61P 17/02: for treating wounds, ulcers, burns, scars, keloids, or the like
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

The patent application relates to new heterocyclic compounds of the general formula (I) in which A, R, R1, R2, X, Y, Z, n and p have the definitions elucidated in more detail in the description, to a process for preparing them and to the use of these compounds as medicaments, particularly as aldosterone synthase inhibitors.

## Claims

### Claim 1

Compound of the general formula
in which
A is aryl or heterocyclyl;
X is CR3R4 or, if Y is CR3R4, is alternatively a bond;
Y is CR3R4, O, S(O)m or NR5;
Z is CR3R4 or
a) if Y is CR3R4, is alternatively O, S(O)m or NR5; or
b) if Y is S(O)m, is alternatively NR5; or
c) if Y is NR5, is alternatively S(O)m;
R is C1-C8-alkoxy, C1-C8-alkyl, halogen, trifluoromethyl, tri-C1-C4-alkylsilyl, deuterium or hydrogen;
R1 is C1-C8-alkoxy, C1-C8-alkoxycarbonyl, C1-C8-alkyl, mono- and di-C1-C8-alkylamino, mono- and di-C1-C8-alkylaminocarbonyl, C0-C8-alkylcarbonyl, amino, carbamoyl, carboxy-C1-C4-alkyl, carboxyl, cyano, halogen, oxo, trifluoromethyl, trifluoromethoxy, heterocyclyl or aryl, which radicals may be substituted by 1-4 C1 -C8-alkoxy, C1-C8-alkoxycarbonyl, C1-C8-alkyl, C0-C8-alkylcarbonyl, tri-C1-C4-alkylsilyl, C1-C8-alkylsulphonyl, aryl, cyano, halogen, heterocyclyl, oxo, trifluoromethyl or trifluoromethoxy;
R2 a) is, independently of one another, C1-C8-alkyl, mono- and di-C1-C8-alkylamino, mono- and di-C1-C8-alkylaminocarbonyl, C0-C8-alkylcarbonyl, C1-C8-alkoxy, C1-C8-alkoxycarbonyl, amino, carbamoyl, carboxy-C1-C4-alkyl, carboxyl, cyano, halogen, oxo, trifluoromethyl, trifluoromethoxy, hydrogen, heterocyclyl or aryl, which radicals may be substituted by 1-4 C1-C8-alkoxy, C1-C8-alkoxycarbonyl, C1-C8-alkyl, C0-C8-alkylcarbonyl, tri-C1-C4-alkylsilyl, C1-C8-alkylsulphonyl, aryl, cyano, halogen, heterocyclyl, oxo, trifluoromethyl or trifluoromethoxy; or
b) together with R1 is a fused-on 5-6-membered heterocyclic ring;
R3 is hydrogen or C1-C8-alkyl;
R4 a) is hydrogen or C1-C8-alkyl; or
b) together with R3 is oxo;
R5 is hydrogen, C1-C8-alkyl or C0-C8-alkylcarbonyl;
m is a number 0, 1 or 2;
n is a number 0, 1 or 2;
p is a number 1 or 2;
and its salts, preferably its pharmaceutically useful salts.

### Claim 2 (depends on 1)

Compound according to claim 1, characterized in that it conforms to the general formula
the definitions of the substituents R, R1, R2, R3, R4, R5 and p being as specified for compounds of the formula (I) according to claim 1, and having a specific configuration at the asymmetric carbon atom labelled “*”.

### Claim 3 (depends on 1)

Compound according to claim 1, wherein R is hydrogen or deuterium.

### Claim 4 (depends on 1)

Compound according to claim 1, wherein R1 is halogen, cyano, trifluoromethyl, heterocyclyl or C0-C8-alkylcarbonyl.

### Claim 5 (depends on 1)

Compound according to claim 1, wherein R2 is, independently of one another, hydrogen, C1-C8-alkyl, cyano or halogen or together with R1 is a fused-on 5- or 6-membered heterocyclic ring.

### Claim 6 (depends on 1)

Compound according to claim 1, wherein R3 and R4 are hydrogen or together are oxo.

### Claim 7 (depends on 1)

Compound according to claim 1, wherein R5 is hydrogen, methyl, formyl or acetyl.

### Claim 8 (depends on 1)

Compound according to claim 1, wherein n is a number 0 or 1.

### Claim 9 (depends on 2)

Compound according to claim 2, wherein
R is hydrogen or deuterium;
R1 is halogen, cyano, trifluoromethyl, heterocyclyl or C0-C8-alkylcarbonyl;
R2 is, independently of one another, hydrogen, C1-C8-alkyl or cyano or together with R1 is a fused-on 5- or 6-membered heterocyclic ring;
R3 and R4 are hydrogen or together are oxo; and
R5 is hydrogen, methyl, formyl or acetyl.

### Claim at position 10

10-12. (canceled)

### Claim 13 (depends on 1)

Method of preventing, delaying the progression of or treating pathological states which are wholly or partly caused by hyperaldosteronism, in a patient, which comprises administering a therapeutically effective amount of a compound of the general formula (I) according to claim 1 to the patient.

### Claim 14 (depends on 1)

Method of preventing, delaying the progression of or treating pathological states which are wholly or partly caused by excessive cortisol release, in a patient, which comprises administering a therapeutically effective amount of a compound of the general formula (I) according to claim 1 to the patient.

### Claim 15 (depends on 1)

Pharmaceutical composition comprising a compound of the general formula (I) according to claim 1 and conventional excipients.

### Claim 16 (depends on 1)

Pharmaceutical combination in the form of a product or kit composed of individual components consisting a) of a compound of the general formula (I) according to claim 1 and b) of at least one pharmaceutical form whose active ingredient has a blood pressure-lowering, an inotropic, a metabolic or a lipid-lowering effect.

### Claim 17 (depends on 2)

Compound according to claim 2, wherein R is hydrogen or deuterium.

### Claim 18 (depends on 2)

Compound according to claim 2, wherein R1 is halogen, cyano, trifluoromethyl, heterocyclyl or C0-C8-alkylcarbonyl.

### Claim 19 (depends on 2)

Compound according to claim 2, wherein R2 is, independently of one another, hydrogen, C1-C8-alkyl, cyano or halogen or together with R1 is a fused-on 5- or 6-membered heterocyclic ring.

### Claim 20 (depends on 2)

Compound according to claim 2, wherein R3 and R4 are hydrogen or together are oxo.

### Claim 21 (depends on 2)

Compound according to claim 2, wherein R5 is hydrogen, methyl, formyl or acetyl.

### Claim 22 (depends on 2)

Method of preventing, delaying the progression of or treating pathological states which are wholly or partly caused by hyperaldosteronism, in a patient, which comprises administering a therapeutically effective amount of a compound of the general formula (I) according to claim 2 to the patient.

### Claim 23 (depends on 2)

Method of preventing, delaying the progression of or treating pathological states which are wholly or partly caused by excessive cortisol release, in a patient, which comprises administering a therapeutically effective amount of a compound of the general formula (I) according to claim 2 to the patient.

### Claim 24 (depends on 2)

Pharmaceutical composition comprising a compound of the general formula (I) according to claim 2 and conventional excipients.

### Claim 25 (depends on 2)

Pharmaceutical combination in the form of a product or kit composed of individual components consisting a) of a compound of the general formula (I) according to claim 2 and b) of at least one pharmaceutical form whose active ingredient has a blood pressure-lowering, an inotropic, a metabolic or a lipid-lowering effect.