5-Amino-4-Hydroxy-7-(Imidazo [1,2-A] Pyridin-6-Ylmethyl)-8-Methyl-Nonamide Derivatives and Related Compounds as Renin Inhibitors for the Treatment of Hypertension

A compound of the formula

• or its salt, or a compound of formula (I), in which one or more atoms are replaced by their stable, nonradioactive isotopes;
• wherein
• X is —CH2—;
• R1 is a mono- to tetrasubstituted, mono- or bicyclic, unsaturated heterocyclic radical having 1 to 4 nitrogen atoms, where the substituents of the said radicals are selected independently of one another from the group consisting of acetamidinyl-C1-6alkyl, 3-acetamidomethylpyrrolidinyl, acyl-C1-6alkoxy-C1-6alkyl, (N-acyl)-C1-6alkoxy-C1-6alkyl-amino, C1-6alkanoyl, C1-6alkanoyloxy, C2-6alkenyl, C2-6alkenyloxy, C2-6alkenyloxy-C1-6alkyl, C1-6alkoxy, C1-6alkoxy-C1-6alkoxy, C1-6alkoxy-C1-6alkoxy-C1-6alkyl, C1-6alkoxy-C1-6alkyl, (N—C1-6alkoxy)-C1-6alkylaminocarbonyl-C1-6alkoxy, (N—C1-6alkoxy)-C1-6alkylaminocarbonyl-C1-6alkyl, C1-6alkoxy-C1-6alkylcarbamoyl, C1-6alkoxy-1-6alkylcarbonyl, C1-6alkoxy-C1-6alkylcarbonylamino, 1-C1-6alkoxy-C1-6alkylimidazol-2-yl, 2-C1-6alkoxy-C1-6alkyl-4-oxoimidazol-1-yl, 3-C1-6alkoxy-C1-6alkylpyrrolidinyl, 1-C1-6alkoxy-C1-6alkyltetrazol-5-yl, 5-C1-6alkoxy-C1-6alkyltetrazol-1-yl, C1-6alkoxyaminocarbonyl-C1-6alkoxy, C1-6alkoxyaminocarbonyl-C1-6alkyl, C1-6alkoxycarbonyl, C1-6alkoxycarbonyl-C1-6alkoxy, C1-6alkoxycarbonyl-C1-6alkyl, C1-6alkoxycarbonylamino, C1-6alkoxycarbonylamino-C1-6alkoxy, C1-6alkoxycarbonyl-amino-C1-6alkyl, C1-6alkyl, (N—C1-6alkyl)-C1-6alkoxy-C1-6alkylcarbamoyl, (N—C1-6alkyl)-C1-6alkoxy-C1-6alkylcarbonylamino, (N—C1-6alkyl)-C1-6alkoxycarbonylamino, (N-C1-6alkyl)-C0-6alkylcarbonylamino-C1-6alkoxy, (N—C1-6alkyl)-C0-6alkylcarbonylamino-C1-6alkyl, (N—C1-6alkyl)-C1-6alkylsulphonylamino-C1-6alkoxy, (N—C1-6alkyl)-C1-6alkylsulphonylamino-C1-6alkyl, C1-6alkylamidinyl, C1-6alkylamino, di-C1-6alkylamino, C1-6alkylamino-C2-6alkoxy, di-C1-6alkylamino-C2-6alkoxy, C1-6alkylamino-C1-6alkyl, C1-6alkylaminocarbonyl, C1-6alkylaminocarbonyl-C1-6alkoxy, di-C1-6alkylaminocarbonyl-C1-6alkoxy, C1-6alkylaminocarbonyl-C1-6alkoxy-C1-6alkyl, C1-6alkylaminocarbonyl-C1-6alkyl, C1-6alkylaminocarbonylamino-C1-6alkoxy, C1-6alkylaminocarbonylamino-C1-6alkyl, di-C1-6alkylaminocarbonyl-C1-6alkyl, di-C1-6alkylamino-C1-6alkyl, C1-6alkyl-carbamoyl, di-C1-6alkylcarbamoyl, C0-6alkylcarbonylamino, C0-6alkylcarbonylamino-C1-6alkoxy, C0-6alkylcarbonylamino-C1-6alkyl, C1-6alkylcarbonyloxy-C1-6alkoxy, C1-6alkylcarbonyloxy-C1-6alkyl, C1-6alkylenedioxy, C1-6alkylsulphonyl, C1-6alkyl-sulphonyl-C1-6alkoxy, C1-6alkylsulphonyl-C1-6alkyl, C1-6alkylsulphonylamino-C1-6alkoxy, C1-6alkylsulphonylamino-C1-6alkyl, amino, amino-C2-7alkoxy, amino-C1-6alkyl, aryl-C1-6alkanoyl, benzoyloxy-C2-6alkoxy, carbamoyl, carbamoyl-C1-6alkoxy, carbamoyl-C1-6alkyl, carboxy, carboxy-C1-6alkoxy, carboxy-C1-6alkoxy-C1-6alkyl, carboxy-C1-6alkyl, cyano, cyano-C1-6alkoxy, cyano-C1-6alkyl, C3-8cycloalkyl-C1-6alkanoyl, C3-8cycloalkyl-C0-6alkoxy, C3-8cycloalkyl-C0-6alkyl, C3-8cycloalkylcarbonylamino, C3-8cycloalkyl-carbonylamino-C1-6alkoxy, C3-8cycloalkylcarbonylamino-C1-6alkyl, 3,4-dihydroxy-pyrrolidinyl, O,N-dimethylhydroxylamino-C1-6alkyl, 2,6-dimethylmorpholinyl, 3,5-dimethylmorpholinyl, dioxanyl, dioxolanyl, dioxolanyl-C1-6alkoxy, 4,4-dioxothiomorpholinyl, dithianyl, dithiolanyl, optionally C1-6alkoxy-, C1-6alkyl-, dihydroxy-C1-6alkylaminocarbonyl- or halogen-substituted furyl, furyl-C1-6alkoxy, furyl-C1-6alkyl, pyridyl, pyridyl-C1-6alkoxy, pyridyl-C1-6alkyl, pyridylamino, pyridyloxy, pyridylthio, pyrimidinyl, pyrimidinyl-C1-6alkoxy, pyrimidinyl-C1-6alkyl, pyrimidinylamino, pyrimidinyloxy, pyrimidinylthio, thienyl, thienyl-C1-6alkoxy or thienyl-C1-6alkyl, halogen, heterocyclyl-C1-6alkanoyl, hydroxy, hydroxy-C2-6alkoxy, hydroxy-C2-6alkoxy-C1-6alkoxy, hydroxy-C2-6alkoxy-C1-6alkyl, hydroxy-C1-6alkyl, (N-hydroxy)-C1-6alkylaminocarbonyl-C1-6alkoxy, (N-hydroxy)-C1-6alkylaminocarbonyl-C1-6alkyl, (N-hydroxy)aminocarbonyl-C1-6alkoxy, (N-hydroxy)aminocarbonyl-C1-6alkyl, hydroxy-benzyloxy, 2-hydroxymethylpyrrolidinyl, 4-hydroxypiperidinyl, 3-hydroxypyrrolidinyl, imidazolyl-C1-6alkoxy, imidazolyl-C1-6alkyl, methoxybenzyloxy, methylenedioxybenzyl-oxy, 2-methylimidazolyl-C1-6alkoxy, 2-methylimidazolyl-C1-6alkyl, 3-methyl-[1,2,4]-oxadiazol-5-yl-C1-6alkoxy, 5-methyl-[1,2,4]-oxadiazol-3-yl-C1-6alkoxy, 3-methyl-[1,2,4]-oxadiazol-5-yl-C1-6alkyl, 5-methyl-[1,2,4]-oxadiazol-3-yl-C1-6alkyl, O-methyloximyl-C1-6alkyl, 4-methylpiperazinyl, N-methylpiperazino-C1-6alkoxy, N-methylpiperazino-C1-6alkoxy-C1-6alkyl, N-methylpiperazino-C1-6alkyl, 5-methyltetrazol-1-yl-C1-6alkoxy, 5-methyltetrazol-1-yl-C1-6alkyl, morpholinyl, morpholino-C1-6alkoxy, morpholino-C1-6alkoxy-C1-6alkyl, morpholino-C1-6alkyl, nitro, [1,2,4]-oxadiazol-5-yl-C1-6alkoxy, [1,2,4]- oxadiazol-5-yl-C1-6alkyl, oxazol-4-yl-C1-6alkoxy, oxazol-4-yl-C1-6alkyl, oxide, oxo, 2-oxoimidazolidinyl, 2-oxo-[1,3]-oxazinyl, 2-oxooxazolidinyl, 2-oxooxazolidinyl-C1-6alkoxy, 2-oxooxazolidinyl-C1-6alkyl, 4-oxopiperidinyl, 2-oxopyrrolidinyl, 2-oxo-pyrrolidinyl-C1-6alkoxy, 2-oxopyrrolidinyl-C1-6alkyl, 2-oxotetrahydropyrimidinyl, 4-oxothiomorpholinyl, optionally C1-6alkoxy-, C1-6alkoxycarbonyl-, C1-6alkyl-, C1-6alkyl-amino-, di-C16alkylamino-, halogen-, hydroxyl-, hydroxy-C1-6alkyl- or trifluoromethyl-substituted phenoxy, phenyl, phenyl-C1-6alkoxy, phenyl-C1-6alkyl or phenylthio, piperazinyl, piperazino-C1-6alkoxy, piperazino-C1-6alkoxy-C1-6alkyl, piperazino-C1-6alkyl, piperidinyl, piperidino-C1-6alkoxy, piperidino-C1-6alkoxy-C1-6alkyl, polyhalogen-C1-6alkoxy, polyhalogen-C1-6alkyl, pyridylcarbamoyloxy-C1-6alkoxy, pyridylcarbonylamino-C1-6alkyl, pyrrolidinyl, pyrrolyl, tetrazol-1-yl-C1-6alkoxy, tetrazol-2-yl-C1-6alkoxy, tetrazol-5-yl-C1-6alkoxy, tetrazol-1-yl-C1-6alkyl, tetrazol-2-yl-C1-6alkyl, tetrazol-5-yl-C1-6alkyl, thiazol-4-yl-C1-6alkoxy, thiazol-4-yl-C1-6alkyl, thiomorpholinyl, [1,2,4]-triazol-1-yl-C1-6alkoxy, [1,2,4]-triazol-4-yl-C1-6alkoxy, [1,2,4]-triazol-1-yl-C1-6alkyl, [1,2,4]-triazol-4-yl-C1-6alkyl and the radical —O—CH2CH(OH)CH2NRx, where NRx is a mono- or di-C1-6alkylamino, N-methylpiperazino, morpholino, piperazino or piperidino radical, and where in the case where R1 is a bicyclic heterocyclic ring system, at least the ring not directly bonded to X is substituted as indicated;
• R2 is C1-6alkyl or C3-6cycloalkyl;
• R3 is independently of one another H, C1-6alkyl, C1-6alkoxycarbonyl or C1-6alkanoyl;
• R4 is C2-6alkenyl, C1-6alkyl, unsubstituted or substituted aryl-C1-6alkyl or C3-8cycloalkyl;
• R5 is -Lm-R6;
• L is C1-6alkylene which is unsubstituted or substituted by 1-4 halogen, or a linker:
• n=0, 1 or 2;
• m=0 or 1;
• R6 is a radical composed of 2 cyclic systems selected from bicyclo[x.y.z]alkyl, spiro[o.p]alkyl, mono- or bioxabicyclo[x.y.z]alkyl or mono- or bioxaspiro[o.p]alkyl, all of which may be substituted by 1-3 substituents selected from C1-6alkyl, C1-6alkoxy, cyano, halogen, C1-6alkoxy-C1-6alkyl, hydroxy-C1-6alkyl or dialkylamino, or
• if m=0:
• is also saturated C3-8heterocyclyl which comprises 1-2 oxygen atoms, substituted by 1-3 substituents selected from C1-6alkyl, C1-6alkoxy, cyano, halogen, C1-6alkoxy-C1-6alkyl, hydroxy-C1-6alkyl or dialkylamino, or
• if m=1:
• is also saturated C3-8heterocyclyl which comprises 1-2 oxygen atoms, unsubstituted or substituted by 1-3 substituents selected from C1-6alkyl, C1-6alkoxy, cyano, halogen, C1-6-alkoxy-C1-6alkyl, hydroxy-C1-6alkyl or dialkylamino;
• o=2, 3, 4, 5 or 6
• p=2, 3, 4, 5 or 6
• x=1, 2, 3, 4 or 5;
• y=1, 2, 3, 4 or 5;
• and
• z=0, 1, 2, 3, 4 or 5;
• where x≧y≧z.