Heterocyclic spiro-compounds as aldosterone synthase inhibitors

1. A compound of the general formula

having a specific configuration at the asymmetric carbon atom labeled “*”,

in which

A is aryl;

U is —C(R 3 )(R 4 )—, S(O) m —, —N(R 5 )— or a bond;

V is —C(R 3 )(R 4 )— or

a) if U is either a bond or —C(R 3 )(R 4 )—, V is alternatively —S(O) m — or —N(R 5 )—,

b) if U is —S(O) m —, V is alternatively —N(R 5 )—, or

c) if U is —N(R 5 )—, V is alternatively —S(O) m —;

W is —C(R 3 )(R 4 )— or

a) if U is either a bond or —C(R 3 )(R 4 )— and V is —C(R 3 )(R 4 )—, W is alternatively —O—, —S(O) m — or —N(R 5 )—,

b) if U is either a bond or —C(R 3 )(R 4 )— and V is —S(O) m —, W is alternatively —N(R 5 )—,

c) if U is either a bond or —C(R 3 )(R 4 )— and V is —N(R 5 )—, W is alternatively —S(O) m —, or

d) if U is —N(R 5 )— and V is —C(O)—, W is alternatively —N(R 5 )—;

R is hydrogen, C 1 -C 8 -alkyl, C 1 -C 8 -alkoxy-C 0 -C 4 -alkyl, halogen, tri-C 1 -C 4 -alkylsilyl, deuterium or trifluoromethyl;

R 1 is C 1 -C 8 -alkyl, C 0 -C 8 -alkylcarbonyl, amino, mono- or di-C 1 -C 8 -alkylamino, C 0 -C 8 -alkyl-carbonylamino, C 0 -C 8 -alkylcarbonyl-C 1 -C 8 -alkylamino, carbamoyl, mono- or di-C 1 -C 8 -alkyl-aminocarbonyl, carboxyl, carboxy-C 1 -C 4 -alkyl, halogen, cyano, oxo, trifluoromethyl, trifluoromethoxy, C 1 -C 8 -alkoxy, or C 1 -C 8 -alkoxycarbonyl, which radicals may be substituted by 1-4 C 1 -C 8 -alkyl, C 0 -C 8 -alkylcarbonyl, halogen, cyano, oxo, trifluoromethyl, C 0 -C 8 -alkylcarbonylamino, C 0 -C 8 -alkylcarbonyl-C 1 -C 8 -alkylamino, carbamoyl, mono- or di-C 1 -C 8 -alkylaminocarbonyl, carboxy-C 0 -C 4 -alkyl, C 1 -C 8 -alkoxy, or C 1 -C 8 -alkoxycarbonyl,

R 2 is hydrogen, C 1 -C 8 -alkyl, C 0 -C 8 -alkylcarbonyl, amino, mono- or di-C 1 -C 8 -alkylamino, C 0 -C 8 -alkylcarbonylamino, C 0 -C 8 -alkylcarbonyl-C 1 -C 8 -alkylamino, carbamoyl, mono- or di-C 1 -C 8 -alkylaminocarbonyl, carboxyl, carboxy-C 1 -C 4 -alkyl, halogen, cyano, oxo, trifluoromethyl, trifluoromethoxy, C 1 -C 8 -alkoxy, or C 1 -C 8 -alkoxycarbonyl, which radicals may be substituted by 1-4 C 1 -C 8 -alkyl, C 0 -C 8 -alkylcarbonyl, halogen, cyano, oxo, trifluoromethyl, trifluoromethoxy, C 0 -C 8 -alkylcarbonylamino, C 0 -C 8 -alkylcarbonyl-C 1 -C 8 -alkylamino, carbamoyl, mono- or di-C 1 -C 8 -alkylaminocarbonyl, carboxy-C 0 -C 4 -alkyl, C 1 -C 8 -alkoxy, or C 1 -C 8 -alkoxycarbonyl;

R 3 is hydrogen or C 1 -C 8 -alkyl;

R 4 a) is hydrogen or C 1 -C 8 -alkyl; or

b) together with R 3 is oxo;

R 5 is hydrogen, C 1 -C 8 -alkyl or C 0 -C 8 -alkylcarbonyl;

m is a number 0, 1 or 2;

p is is a number 1;

or its pharmaceutically useful salt.

2. A compound according to claim 1 , wherein R is hydrogen or deuterium.

3. A compound according to claim 1 , wherein R 1 is C 1 -C 8 -alkyl, C 0 -C 8 -alkylcarbonyl, halogen, cyano, oxo, trifluoromethyl, trifluoromethoxy, C 0 -C 8 -alkylcarbonylamino, C 0 -C 8 -alkylcarbonyl-C 1 -C 8 -alkylamino, carbamoyl, mono- or di-C 1 -C 8 -alkylaminocarbonyl, carboxy-C 0 -C 4 -alkyl, C 1 -C 8 -alkoxy, or C 1 -C 8 -alkoxycarbonyl.

4. A compound according to claim 1 , wherein R 2 is hydrogen, halogen, cyano, trifluoromethyl, trifluoromethoxy, or C 1 -C 1-8 -alkyl.

5. A compound according to claim 1 , wherein

R is hydrogen or deuterium;

R 1 is formyl, acetyl, halogen, or cyano; and

R 2 is, independently of one another, hydrogen, halogen, cyano or, C 1 -C 8 -alkyl.

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

7. A pharmaceutical combination in the form of a product or kit composed of individual components consisting a) of a compound of the 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.

8. A compound according to claim 3 , wherein R 1 is formyl, acetyl, or cyano.

9. A compound according to claim 4 , wherein R 2 is hydrogen, halogen, cyano or C 1 -C 8 -alkyl.