IP Library › Granted Patent US 7,687,495
Granted Patent B2
US 7,687,495 · App. 12/076,221 · Granted Mar 30, 2010

Substituted piperidines

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Quick Facts
Patent No.
US 7,687,495
App. No.
12/076,221
Granted
Mar 30, 2010
Kind
B2
Abstract

Substituted piperidines of formulae (I) and (II) with the substituent definitions as explained in the specification. The compounds are suitable in particular as renin inhibitors and are highly potent.

Claims (182)

1. A compound of the formula (I)

wherein

R is C 2-8 -alkenyl, C 1-8 -alkyl, C 2-8 -alkynyl, C 0-8 -alkyl-carbonyl-amino-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-8 -alkyl, C 1-8 -alkyl-sulfonyl-C 1-8 -alkyl, unalkylated or N-mono- or N,N-di-C 1-8 -alkylated carbamoyl-C 0-8 -alkyl, unalkylated or O—C 1-8 -alkylated carboxyl-C 0-8 -alkyl, unalkylated or N and/or N′ mono-, di- or tri-C 1-8 -alkylated ureido-C 1-8 -alkyl or heterocyclylcarbonyl-C 0-8 -alkyl, each of said radicals being substituted by 1-4 C 1-8 -alkoxy or hydroxyl;

R 1 is benzoxazinyl;

R 2 is acenaphthyl, cyclohexyl, diazinyl, furyl, imidazolyl, naphthyl, oxadiazolyl, oxazolyl, phenyl, pyrazinyl, pyridyl, pyrimidinyl, pyrrolyl, oxopyridinyl, tetrazolyl, thienyl, or triazolyl, each of said radicals may be substituted by 1-3 C 1-8 -alkanoyloxy-C 1-8 -alkyl, C 2-8 -alkenyloxy, C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxycarbonyl, C 1-8 -alkoxycarbonyloxy-C 1-8 -alkyl, C 1-8 -alkyl, carboxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkylsulfanyl, C 1-8 -alkylsulfanyl, C 1-8 -alkylsulfanyl-C 1-8 -alkoxy, C 1-8 -alkylsulfanyl-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkylsulfanyl-C 1-8 -alkyl, cyano, cyano-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkoxy, C 1-6 -alkoxy-C 0-6 -alkyl-C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkyl, halo-C 1-8 -alkyl, halogen, hydroxy-C 1-8 -alkyl, hydroxyl, oxide, trifluoromethoxy or trifluoromethyl groups, or a C 1-8 -alkylenedioxy group, and/or by an L1-T1-L2-T2-L3-T3-L4-T4-L5-U radical;

L1, L2, L3, L4 and L5 are each independently a bond, C 1-8 -alkylene, C 2-8 -alkenylene or C 2-8 -alkynylene, C 3-8 -cycloalkene or are absent;

T1, T2, T3 and T4 are each independently

(a) a bond, or are absent, or are one of the groups

(b) —CH(OH)—;

(c) —CH(OR 6 )—;

(d) —CH(NR 5 R 6 )—;

(e) —CO—;

(f) —CR 7 R 8 —;

(g) —O— or —NR 6 —;

(h) —S(O) 0-2 —;

(i) —SO 2 NR 6 —;

(j) —NR 6 SO 2 —;

(k) —CONR 6 —;

(l) —NR 6 CO—;

(m) —O—CO—;

(n) —CO—O—;

(o) —O—CO—O—;

(p) —O—CO—NR 6 —;

(q) —N(R 6 )—CO—N(R 6 )—;

(r) —N(R 6 )—CO—O—;

(s) pyrrolidinylene, piperidinylene or piperazinylene;

(t) —C(R 11 )(R 12 )—,

wherein the bonds starting from (b)-(t) lead to a saturated or aromatic carbon atom of the adjacent group if the bond starts from a heteroatom, and where not more than two (b)-(f) groups, three (g)-(h) groups and one (i)-(t) group are present;

R 3 is hydrogen, hydroxyl, C 1-8 -alkoxy or C 2-8 -alkenyloxy;

R 4 is hydrogen, C 2-8 -alkenyl, C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkyl, optionally (N—C 1-8 -alkyl)-C 1-8 -alkoxycarbonyl-amino-C 1-8 -alkoxy, optionally (N—C 1-8 -alkyl)-C 1-8 -alkylcarbonyl-amino-C 1-8 -alkoxy, optionally (N-mono- or N,N-di-C 1 -C 8 -alkyl)-amino-C 1-8 -alkoxy, benzyl, C 3-8 -cycloalkyloxy, C 3-8 -cycloalkyloxy-C 1-8 -alkoxy, heterocyclyl-C 0-8 -alkoxy, heterocyclyloxy-C 1-8 -alkoxy, hydroxy, hydroxy-C 1-8 -alkoxy-C 1-8 -alkoxy, hydroxy-C 1-8 -alkyl, oxo, or a R 4a -Z1-X1- group, wherein R 4a is

(a) H—;

(b) C 1-8 -alkyl-;

(c) C 2-8 -alkenyl-;

(d) hydroxy-C 1-8 -alkyl-;

(e) polyhydroxy-C 1-8 -alkyl-;

(f) C 1-8 -alkyl-O—C 1-8 -alkyl-;

(g) aryl-;

(h) heterocyclyl-;

(i) arylalkyl-;

(j) heterocyclylalkyl-;

(k) aryloxyalkyl-;

(l) heterocyclyloxyalkyl-;

(m) (R 5 ,R 6 )N—(CH 2 ) 1-3 —;

(n) (R 5 ,R 6 )N—;

(o) C 1-8 -alkyl-S(O) 0-2 —;

(p) aryl-S(O) 0-2 —;

(q) heterocyclyl-S(O) 0-2 —;

(r) HO—SO 3 — or salts thereof;

(s) H 2 N—C(NH)—NH—;

(t) NC—,

and the bonds starting from (n)-(t) lead to a carbon atom of the adjacent group and this carbon atom is saturated if the bond starts from a heteroatom;

Z1 is

(a) a bond, is absent, or is one of the groups:

(b) —C 1-8 -alkylene-;

(c) —C 2-8 -alkenylene-;

(d) —O—, —N(R 11 )—, —S(O) 0-2 —;

(e) —CO—;

(f) —O—CO—;

(g) —O—CO—O—;

(h) —O—CO—N(R 11 )—;

(i) —N(R 11 )—CO—O—;

(j) —CO—N(R 11 )—;

(k) —N(R 11 )—CO—;

(l) —N(R 11 )—CO—N(R 11 )—;

(m) —CH(OR 9 )—

and the bonds starting from (d) and (f)-(m) lead to a carbon atom of the adjacent group and this carbon atom is saturated if the bond starts from a heteroatom;

X1 is

(a) a bond, is absent, or is one of the groups:

(b) —O—;

(c) —N(R 11 )—;

(d) —S(O) 0-2 —;

(e) —(CH 2 ) 1-3 —;

or R 3 and R 4 in formula (I) together are a bond;

R 5 and R 6 are each independently hydrogen, C 1-8 -alkyl, C 2-8 -alkenyl, aryl-C 1-8 -alkyl or acyl, or, together with the nitrogen atom to which they are bonded, are a 5- or 6-membered heterocyclic ring which may contain an additional nitrogen, oxygen or sulfur atom or a —SO— or —SO 2 — group, and the additional nitrogen atom is unsubstituted or substituted by C 1-8 -alkyl radicals;

R 7 and R 8 , together with the carbon atom to which they are bonded, are a 3-7-membered ring which may contain one or two —O— or —S— atoms or —SO— or —SO 2 — groups;

R 9 is hydrogen, C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkyl, acyl or arylalkyl;

R 10 is carboxyalkyl, alkoxycarbonylalkyl, alkyl or hydrogen;

R 11 is hydrogen or C 1-8 -alkyl;

R 12 is hydrogen or C 1-8 -alkyl;

Q is absent;

U is hydrogen, C 1-8 -alkyl, cyano, unsubstituted or substituted C 3-8 -cycloalkyl, aryl or heterocyclyl;

W is oxygen or sulfur;

X is a bond, oxygen or sulfur, or is a >CH—R 11 , >CHOR 9 , —O—CO—, >CO, >C═NOR 10 , —O—CHR 11 — or —O—CHR 11 —CO—NR 9 — group and the bond starting from an oxygen or sulfur atom leads to a saturated carbon atom of the Z group or to R 1 ;

Z is C 1-8 -alkylene, C 2-8 -alkenylene, hydroxy-C 1-8 -alkylidene, —O—, —S—, —O-alk-, —S-alk-, -alk-O—, -alk-S— or -alk-NR 9 —, where alk is C 1-8 -alkylene; and wherein

(a) if Z is —O— or —S—, X is >CH—R 11 and either R 2 contains an L1-T1-L2-T2-L3-T3-L4-T4-L5-U substituent or R 4 is a substituent other than hydrogen as defined above;

(b) if Z is —O-alk- or —S-alk-, X is >CH—R 11 ; and

(c) if X is a bond, Z is C 2-8 -alkenylene, -alk-O— or -alk-S—;

m is 0 or 1;

n is 0 or 1;

or salt or prodrug thereof, or where one or more atoms are replaced by their stable, non-radioactive isotopes.

2. A compound according to claim 1 of the formula (IA)

wherein R, R 1 , R 2 , R 3 , R 4 , Q, W, X, Z, n and m are each as defined for the compounds of the formula (I) according to claim 1 .

3. A compound according to claim 1 , wherein

R is C 2-8 -alkenyl, C 1-8 -alkyl, C 2-8 -alkynyl, C 0-8 -alkyl-carbonyl-amino-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-8 -alkyl, C 1-8 -alkyl-sulfonyl-C 0-8 -alkyl, unalkylated or N-mono- or N,N-di-C 1-8 -alkylated carbamoyl-C 0-8 -alkyl, unalkylated or O—C 1-8 -alkylated carboxyl-C 0-8 -alkyl, unalkylated or N and/or N′ mono-, di- or tri-C 1-8 -alkylated ureido-C 0-8 -alkyl or heterocyclylcarbonyl-C 0-8 -alkyl, each of said radicals being substituted by 1-4 C 1-8 -alkoxy or hydroxyl;

R 1 is benzoxazinyl;

R 2 is phenyl, cyclohexyl, tetrazolyl, naphthyl or acenaphthyl, each of said radicals may be unsubstituted or substituted by 1-3 C 1-8 -alkanoyloxy-C 1-8 -alkyl, C 2-8 -alkenyloxy, C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxycarbonyl, C 1-8 -alkoxycarbonyloxy-C 1-8 -alkyl, C 1-8 -alkyl, carboxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkylsulfanyl, C 1-8 -alkylsulfanyl, C 1-8 -alkylsulfanyl-C 1-8 -alkoxy, C 1-8 -alkylsulfanyl-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkylsulfanyl-C 1-8 -alkyl, cyano, cyano-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkoxy, C 1-6 -alkoxy-C 0-6 -alkyl-C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkyl, halo-C 1-8 -alkyl, halogen, hydroxy-C 1-8 -alkyl, hydroxyl, oxide, trifluoromethoxy or trifluoromethyl groups, or a C 1-8 -alkylenedioxy group, and/or by an L1-T1-L2-T2-L3-T3-L4-T4-L5-U radical; or naphthyl or acenaphthyl;

L1, L2, L3, L4 and L5 are each independently a bond, C 1-8 -alkylene, C 2-8 -alkenylene or C 2-8 -alkynylene, C 3-8 -cycloalkene or are absent;

T1, T2, T3 and T4 are each independently

(a) a bond, or are absent, or are one of the groups:

(b) —CH(OH)—;

(c) —CH(OR 6 )—;

(d) —CH(NR 5 R 6 )—;

(e) —O—;

(f) —CR 7 R 8 ;

(g) —O— or —NR 6 —;

(h) —S(O) 0-2 —;

(I) —SO 2 NR 6 —;

(j) —NR 6 SO 2 —;

(k) —CONR 6 —;

(l) —NR 6 CO—;

(m) —O—CO—;

(n) —CO—O—;

(o) —O—CO—O—;

(p) —O—CO—NR 6 —;

(q) —N(R 6 )—CO—N(R 6 )—;

(r) —N(R 6 )—CO—O—;

(s) pyrrolidinylene, piperidinylene or piperazinylene;

(t) —C(R 11 )(R 12 )—,

wherein the bonds starting from (b)-(t) lead to a saturated or aromatic carbon atom of the adjacent group if the bond starts from a heteroatom, and where not more than two (b)-(f) groups, three (g)-(h) groups and one (i)-(t) group are present;

R 3 is hydrogen, hydroxyl, C 1-8 -alkoxy or C 2-8 -alkenyloxy;

R 4 is hydrogen, C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkyl, optionally (N—C 1-8 -alkyl)-C 1-8 -alkoxycarbonyl-amino-C 1-8 -alkoxy, optionally (N—C 1-8 -alkyl)-C 1-8 -alkylcarbonyl-amino-C 1-8 -alkoxy, optionally (N-mono- or N,N-di-C 1 -C 9 -alkyl)-amino-C 1-8 -alkoxy, C 3-8 -cycloalkyloxy, C 3-8 -cycloalkyloxy-C 1-8 -alkoxy, heterocyclyl-C 0-8 -alkoxy, heterocyclyloxy-C 1-8 -alkoxy, hydroxy, oxo or hydroxy-C 1-8 -alkoxy-C 1-8 -alkoxy;

R 5 and R 6 are each independently hydrogen, C 1-8 -alkyl or acyl, or, together with the nitrogen atom to which they are bonded, are a 5- or 6-membered heterocyclic ring which may contain an additional nitrogen, oxygen or sulfur atom;

R 7 and R 8 , together with the carbon atom to which they are bonded, are a 3-7-membered ring which may contain one or two —O— or —S— atoms;

R 9 is hydrogen, C 1-8 -alkyl, acyl or arylalkyl;

U is hydrogen, C 1-8 -alkyl, C 3-8 -cycloalkyl, cyano, aryl or heterocyclyl;

Q is absent;

X is a bond, oxygen, sulfur or is a >CHR 11 , >CHOR 9 , —O—CO—, >CO or —O—CH—R 11 —CO—NR 9 — group;

W is oxygen or sulfur if R 3 is hydrogen;

Z is C 1-8 -alkylene or -alk-O—; wherein, if X is a bond, Z is -alk-O—;

n is 0 or 1;

m is 0 or 1;

or a pharmaceutically useable salt thereof.

4. A compound according to claim 1 , wherein

R 2 is phenyl or halophenyl each substituted by C 2-8 -alkenyloxy, C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkyl-amino-C 1-8 -alkyl, C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkylsulfanyl, C 1-8 -alkylsulfanyl, C 1-8 -alkylsulfanyl-C 1-8 -alkyl, C 1-8 -alkylsulfanyl-C 1-8 -alkoxy, C 1-8 -alkylsulfanyl-C 1-8 -alkoxy-C 1-8 -alkyl, C 3-8 -cycloalkylsulfanyl-C 1-8 -alkyl, C 1-8 -alkylsulfonyl-C 1-8 -alkoxy-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-6 -alkoxy, C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkoxy, C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkyl, C 1-6 -alkoxy-C 0-6 -alkyl-C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 1-8 -alkylamino-C 1-8 -alkyl, halogen, heterocyclyl-C 0-6 -alkoxy, heterocyclyl-C 0-6 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkylamino-C 1-8 -alkyl, N-(halo-phenyl)pyrrolidinyloxy, N-(halo-phenyl)pyrrolidinyloxy-C 1-8 -alkyl, C 1-8 -alkoxybenzyloxy-C 1-8 -alkoxy, C 1-8 -alkoxyphenoxy-C 1-8 -alkoxy, C 1-8 -alkoxyphenoxy-C 1-8 -alkyl, C 1-8 -alkoxyphenyl-C 1-8 -alkoxy-C 1-8 -alkoxy, halobenzyloxy-C 1-8 -alkoxy, halophenoxy-C 1-8 -alkoxy, halophenoxy-C 1-8 -alkoxy-C 1-8 -alkyl, halophenoxy-C 1-8 -alkyl, halophenyl-C 1-8 -alkoxy-C 1-8 -alkoxy or C 1-8 -alkylbenzyloxy-C 1-8 -alkoxy, whereby at least one substituent is in the para-position relative to the bond of R 2 to the rest of the molecule.

5. A compound according to claim 1 , wherein m is 0.

6. A pharmaceutical composition comprising a compound of the formula (I) according to claim 1 , and a pharmaceutically inert excipient.

7. A compound according to claim 2 , wherein

R is C 2-8 -alkenyl, C 1-8 -alkyl, C 2-8 -alkynyl, C 0-8 -alkyl-carbonyl-amino-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-8 -alkyl, C 1-8 -alkyl-sulfonyl-C 0-8 -alkyl, unalkylated or N-mono- or N,N-di-C 1-8 -alkylated carbamoyl-C 0-8 -alkyl, unalkylated or O—C 1-8 -alkylated carboxyl-C 0-8 -alkyl, unalkylated or N and/or N′ mono-, di- or tri-C 1-8 -alkylated ureido-C 0-8 -alkyl or heterocyclylcarbonyl-C 0-8 -alkyl, each of said radicals being substituted by 1-4 C 1-8 -alkoxy or hydroxyl;

R 1 is benzoxazinyl;

R 2 is phenyl, cyclohexyl, tetrazolyl, naphthyl or acenaphthyl, each of said radicals may be unsubstituted or substituted by 1-3 C 1-8 -alkanoyloxy-C 1-8 -alkyl, C 2-8 -alkenyloxy, C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxycarbonyl, C 1-8 -alkoxycarbonyloxy-C 1-8 -alkyl, C 1-8 -alkyl, carboxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkylsulfanyl, C 1-8 -alkylsulfanyl, C 1-8 -alkylsulfanyl-C 1-8 -alkoxy, C 1-8 -alkylsulfanyl-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkylsulfanyl-C 1-8 -alkyl, cyano, cyano-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkoxy, C 1-6 -alkoxy-C 0-6 -alkyl-C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkyl, halo-C 1-8 -alkyl, halogen, hydroxy-C 1-8 -alkyl, hydroxyl, oxide, trifluoromethoxy or trifluoromethyl groups, or a C 1-8 -alkylenedioxy group, and/or by an L1-T1-L2-T2-L3-T3-L4-T4-L5-U radical; or naphthyl or acenaphthyl;

L1, L2, L3, L4 and L5 are each independently a bond, C 1-8 -alkylene, C 2-8 -alkenylene or C 2-8 -alkynylene, C 3-8 -cycloalkene or are absent;

T1, T2, T3 and T4 are each independently

(a) a bond, or are absent, or are one of the groups:

(b) —CH(OH)—;

(c) —CH(OR 6 )—;

(d) —CH(NR 5 R 6 )—;

(e) —CO—;

(f) —CR 7 R 8 —;

(g) —O— or —NR 6 —;

(h) —S(O) 0-2 —;

(I) —SO 2 NR 6 —;

(j) —NR 6 SO 2 —;

(k) —CONR 6 —;

(l) —NR 6 CO—;

(m) —O—CO—;

(n) —CO—O—;

(o) —O—CO—O—;

(p) —O—CO—NR 6 —;

(q) —N(R 6 )—CO—N(R 6 )—;

(r) —N(R 6 )—CO—O—;

(s) pyrrolidinylene, piperidinylene or piperazinylene;

(t) —C(R 11 )(R 12 )—,

wherein the bonds starting from (b)-(t) lead to a saturated or aromatic carbon atom of the adjacent group if the bond starts from a heteroatom, and where not more than two (b)-(f) groups, three (g)-(h) groups and one (i)-(t) group are present;

R 3 is hydrogen, hydroxyl, C 1-8 -alkoxy or C 2-8 -alkenyloxy;

R 4 is hydrogen, C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkyl, optionally (N—C 1-8 -alkyl)-C 1-8 -alkoxycarbonyl-amino-C 1-8 -alkoxy, optionally (N—C 1-8 -alkyl)-C 1-8 -alkylcarbonyl-amino-C 1-8 -alkoxy, optionally (N-mono- or N,N-di-C 1 -C 8 -alkyl)-amino-C 1-8 -alkoxy, C 3-8 -cycloalkyloxy, C 3-8 -cycloalkyloxy-C 1-8 -alkoxy, heterocyclyl-C 0-8 -alkoxy, heterocyclyloxy-C 1-8 -alkoxy, hydroxy, oxo or hydroxy-C 1-8 -alkoxy-C 1-8 -alkoxy;

R 5 and R 6 are each independently hydrogen, C 1-8 -alkyl or acyl, or, together with the nitrogen atom to which they are bonded, are a 5- or 6-membered heterocyclic ring which may contain an additional nitrogen, oxygen or sulfur atom;

R 7 and R 8 , together with the carbon atom to which they are bonded, are a 3-7-membered ring which may contain one or two —O— or —S— atoms;

R 9 is hydrogen, C 1-8 -alkyl, acyl or arylalkyl;

U is hydrogen, C 1-8 -alkyl, C 3-8 -cycloalkyl, cyano, aryl or heterocyclyl;

Q is absent;

X is a bond, oxygen, sulfur or is a >CHR 11 , >CHOR 9 , —O—CO—, >CO or —O—CH—R 11 —CO—NR 9 — group;

W is oxygen or sulfur if R 3 is hydrogen;

Z is C 1-8 -alkylene or -alk-O—; wherein, if X is a bond, Z is -alk-O—;

n is 0 or 1;

m is 0 or 1;

or a pharmaceutically useable salt thereof.

8. A compound according to claim 2 , wherein

R 2 is phenyl or halophenyl each substituted by C 2-8 -alkenyloxy, C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy, C 1-8 -alkoxy-C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkyl-amino -C 1-8 -alkyl, C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkylsulfanyl, C 1-8 -alkylsulfanyl, C 1-8 -alkylsulfanyl-C 1-8 -alkyl, C 1-8 -alkylsulfanyl-C 1-8 -alkoxy, C 1-8 -alkylsulfanyl-C 1-8 -alkoxy-C 1-8 -alkyl, C 3-8 -cycloalkylsulfanyl-C 1-8 -alkyl, C 1-8 -alkylsulfonyl-C 1-8 -alkoxy-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 0-6 -alkoxy, C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkoxy, C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkyl, C 1-6 -alkoxy-C 0-6 -alkyl-C 3-8 -cycloalkyl-C 0-6 -alkoxy-C 1-8 -alkyl, C 3-8 -cycloalkyl-C 1-8 -alkylamino-C 1-8 -alkyl, halogen, heterocyclyl-C 0-6 -alkoxy, heterocyclyl-C 0-6 -alkoxy-C 1-8 -alkyl, C 1-8 -alkoxy-C 1-8 -alkylamino-C 1-8 -alkyl, N-(halo-phenyl)pyrrolidinyloxy, N-(halo-phenyl)pyrrolidinyloxy-C 1-8 -alkyl, C 1-8 -alkoxybenzyloxy-C 1-8 -alkoxy, C 1-8 -alkoxyphenoxy-C 1-8 -alkoxy, C 1-8 -alkoxyphenoxy-C 1-8 -alkyl, C 1-8 -alkoxyphenyl-C 1-8 -alkoxy-C 1-8 -alkoxy, halobenzyloxy-C 1-8 -alkoxy, halophenoxy-C 1-8 -alkoxy, halophenoxy-C 1-8 -alkoxy-C 1-8 -alkyl, halophenoxy-C 1-8 -alkyl, halophenyl-C 1-8 -alkoxy-C 1-8 -alkoxy or C 1-8 -alkylbenzyloxy-C 1-8 -alkoxy, whereby at least one substituent is in the para-position relative to the bond of R 2 to the rest of the molecule.

9. A compound according to claim 2 , wherein m is 0.

10. A pharmaceutical composition comprising a compound of the formula (IA) according to claim 2 , and a pharmaceutically inert excipient.

11. A method for treating hypertension, glaucoma, cardiac infarction, or restenoses, which comprises administering a therapeutically effective amount of a compound of formula (I) according to claim 1 to a patient in need thereof.

12. A method for treating hypertension, glaucoma, cardiac infarction, or restenoses, which comprises administering a therapeutically effective amount of a compound of formula (IA) according to claim 2 to a patient in need thereof.

Assignments (1)
MERGER Recorded Feb 9, 2010
From: SPEEDEL EXPERIMENTA AG
To: NOVARTIS AG
Reel/Frame 023920/0239 →