US2011201564A1PendingUtilityA1
Substituted 7-sulfanylmethyl, 7-sulfinylmethyl and 7-sulfonylmethyl indoles and use thereof
Est. expiryJun 25, 2028(~1.9 yrs left)· nominal 20-yr term from priority
Inventors:Peter KolkhoeAstrid BrünsKai ThedeKarl-Heinz SchlemmerAlexander HillischDieter LangMichael GerischAndreas GöllerRolf GrosserCarsten SchmeckElisabeth WolteringOlaf PrienHolger PaulsenArmin Kern
A61P 9/10A61P 9/00A61P 43/00A61P 5/42A61P 9/12A61P 9/04A61P 1/16A61P 13/12C07D 209/12C07D 209/18C07D 209/10C07D 409/06C07D 405/06C07D 209/26A61K 31/404
57
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The present application relates to novel 7-sulfanylmethyl-, 7-sulfinylmethyl- and 7-sulfonylmethylindole derivatives, processes for the preparation thereof, the use thereof alone or in combinations for the treatment and/or prevention of diseases, and the use thereof for the manufacture of medicaments for the treatment and/or prevention of diseases, especially for the treatment and/or prevention of cardiovascular disorders.
Claims
exact text as granted — not AI-modified1 - 16 . (canceled)
17 . A method for the treatment and/or prophylaxis of aldosteronism, high blood pressure, acute and chronic heart failure, the sequelae of a myocardial infarction, cirrhosis of the liver, renal failure and stroke, comprising a step of administering an effective amount of a compound of formula (I) to a patient in need thereof, wherein the compound of formula (I) is:
in which
A is —S—, —S(═O)— or —S(═O) 2 —.
R 1 is (C 1 -C 4 )-alkyl or cyclopropyl,
R 2 is hydrogen, fluorine or chlorine,
R 3 is hydrogen, fluorine, chlorine or methyl,
R 4 is hydrogen or fluorine,
R 5 is a group of the formula
where
# is the point of attachment to the indole,
and
D is —CH 1 —, —O—, —CH 2 —CH 2 — or —CH 2 —O—,
R 6 is (C 1 -C 4 )-alkyl or (C 3 -C 6 )-cycloalkyl,
in which (C 1 -C 4 )-alkyl may be substituted by 1 to 3 substituents independently of one another selected from the group of fluorine, trifluoromethyl, hydroxy and cyano,
and
in which (C 3 -C 6 )-cycloalkyl may be substituted by 1 to 3 substituents independently of one another selected from the group of fluorine, hydroxy and cyano,
R 7 is hydrogen, halogen, (C 1 -C 4 )-alkyl, trifluoromethyl or (C 1 -C 4 alkoxy,
R 8 is hydrogen, halogen, methyl or trifluoromethyl,
R 9 is phenyl, naphthyl or 5- to 10-membered heteroaryl,
in which phenyl, naphthyl and 5- to 10-membered heteroaryl may be substituted by 1 to 3 substituents independently of one another selected from the group of halogen, cyano, (C 1 -C 4 )-alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, (C 1 -C 4 )-alkoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy and trifluoromethylthio,
or
in which two substituents bonded on adjacent carbon atoms of a phenyl ring together form a group of the formula —O—CH 2 —O—, —O—CHF—O—, —O—CF 2 —O—, —O—CH 2 —CH 2 —O— or —O—CF 2 —CF 2 —,
R 10 is (C 1 -C 6 )-alkyl, (C 3 -C 7 )-cycloalkyl or phenyl,
in which (C 1 -C 6 )-alkyl may be substituted by 1 to 3 substituents independently of one another selected from the group of fluorine, fluoromethyl, difluoromethyl, trifluoromethyl, hydroxy and cyano,
and
in which (C 3 -C 7 )-cycloalkyl may be substituted by 1 to 3 substituents independently of one another selected from the group of fluorine, hydroxy and cyano,
and
in which phenyl may be substituted by 1 to 3 substituents independently of one another selected from the group of halogen, cyano, (C 1 -C 4 )-alkyl, fluoromethyl, difluoromethyl, trifluoromethyl, (C 1 -C 4 )-alkoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy and trifluoromethylthio,
R 11 is hydrogen, methyl, ethyl, trifluoromethyl or cyclopropyl,
and salts thereof.
18 . The method of claim 17 , wherein in the compound formula (I):
A is —S(═O)— or —S(═O) 2 —, R 1 is methyl or ethyl, R 2 is hydrogen or fluorine, R 3 is hydrogen or fluorine, R 4 is hydrogen, R 5 is a group of the formula
where
# is the point of attachment to the indole,
and
R 9 is phenyl, naphthyl or benzothienyl,
in which phenyl, naphthyl and benzothienyl may be substituted by 1 to 3 substituents independently of one another selected from the group of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl and methoxy,
or
in which two substituents bonded to adjacent carbon atoms of a phenyl ring together form a group of the formula —O—CH 2 —O— or —O—CF 2 —O—,
R 10 is 1-cyanoeth-2-yl, 1-cyano-1-methyleth-2-yl, 1-cyano-2-methyleth-2-yl, 1-cyano-1,2-dimethyleth-2-yl, 1-cyano-2,2-dimethyleth-2-yl, 1-cyanoprop-3-yl, 1-cyano-1-methylprop-3-yl, 1-cyano-2-methylprop-3-yl, 1-cyano-3-methylprop-3-yl, 1-cyano-2,3-dimethylprop-3-yl, 1-hydroxyeth-2-yl, 1-hydroxy-1-methyleth-2-yl, 1-hydroxy-2-methyleth-2-yl, 1-hydroxy-1,2-dimethyleth-2-yl, 1-hydroxy-2,2-dimethyleth-2-yl, 1-hydroxyprop-3-yl, 1-hydroxy-1-methylprop-3-yl, 1-hydroxy-2-methylprop-3-yl, 1-hydroxy-3-methylprop-3-yl, 1-hydroxy-2,3-dimethylprop-3-yl, cyclopropyl, 1-cyanocycloprop-2-yl, 1-hydroxycycloprop-2-yl or phenyl,
in which 1-cyanoeth-2-yl, 1-cyano-1-methyleth-2-yl, 1-cyano-2-methyleth-2-yl, 1-cyano-1,2-dimethyleth-2-yl, 1-cyano-2,2-dimethyleth-2-yl, 1-cyanoprop-3-yl, 1-cyano-1-methylprop-3-yl, 1-cyano-2-methylprop-3-yl, 1-cyano-3-methylprop-3-yl, 1-cyano-2,3-dimethylprop-3-yl, 1-hydroxyeth-2-yl, 1-hydroxy-1-methyleth-2-yl, 1-hydroxy-2-methyleth-2-yl, 1-hydroxy-1,2-dimethyleth-2-yl, 1-hydroxy-2,2-dimethyleth-2-yl, 1-hydroxyprop-3-yl, 1-hydroxy-1-methylprop-3-yl, 1-hydroxy-2-methylprop-3-yl, 1-hydroxy-3-methylprop-3-yl, 1-hydroxy-2,3-dimethylprop-3-yl, cyclopropyl, 1-cyanocycloprop-2-yl and 1-hydroxycycloprop-2-yl may be substituted by 1 or 2 fluorine substituents,
and
in which phenyl may be substituted by 1 or 2 substituents independently of one another selected from the group of fluorine, chlorine, cyano and methyl,
R 11 is hydrogen,
and salts thereof.
19 . The method of claim 17 , wherein in the compound of formula (I),
A is —S(═O)— or —S(═O) 2 —, R 11 is methyl or ethyl, R 2 is hydrogen or fluorine, R 3 is hydrogen or fluorine, R 4 is hydrogen, R 5 is a group of the formula
where
# is the point of attachment to the indole,
and
D is —CH 2 — or —CH 2 —O—,
R 6 is (C 1 -C 4 )-alkyl or (C 3 -C 6 )-cycloalkyl,
in which (C 1 -C 4 )-alkyl and (C 3 -C 6 )-cycloalkyl may be substituted by 1 or 2 fluorine substituents,
and
in which (C 1 -C 4 )-alkyl may be substituted by a substituent selected from the group of hydroxy and cyano,
and
in which (C 3 -C 6 )-cycloalkyl may be substituted by a substituent selected from the group of hydroxy and cyano,
R 7 is hydrogen, fluorine, chlorine, methyl or trifluoromethyl,
R 8 is hydrogen, fluorine, chlorine, methyl or trifluoromethyl,
R 9 is phenyl, naphthyl or benzothienyl,
in which phenyl, naphthyl and benzothienyl may be substituted by 1 to 3 substituents independently of one another selected from the group of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl and methoxy,
or
in which two substituents bonded to adjacent carbon atoms of a phenyl ring together form a group of the formula —O—CH 2 —O— or —O—CF 2 —O—,
R 10 is 1-cyanoeth-2-yl, 1-cyano-1-methyleth-2-yl, 1-cyano-2-methyleth-2-yl, 1-cyano-1,2-dimethyleth-2-yl, 1-cyano-2,2-dimethyleth-2-yl, 1-cyanoprop-3-yl, 1-cyano-1-methylprop-3-yl, 1-cyano-2-methylprop-3-yl, 1-cyano-3-methylprop-3-yl, 1-cyano-2,3-dimethylprop-3-yl, 1-hydroxyeth-2-yl, 1-hydroxy-1-methyleth-2-yl, 1-hydroxy-2-methyleth-2-yl, 1-hydroxy-1,2-dimethyleth-2-yl, 1-hydroxy-2,2-dimethyleth-2-yl, 1-hydroxyprop-3-yl, 1-hydroxy-1-methylprop-3-yl, 1-hydroxy-2-methylprop-3-yl, 1-hydroxy-3-methylprop-3-yl, 1-hydroxy-2,3-dimethylprop-3-yl, (C 3 -C 7 )-cycloalkyl or phenyl,
in which 1-cyanoeth-2-yl, 1-cyano-1-methyleth-2-yl, 1-cyano-2-methyleth-2-yl, 1-cyano-1,2-dimethyleth-2-yl, 1-cyano-2,2-dimethyleth-2-yl, 1-cyanoprop-3-yl, 1-cyano-1-methylprop-3-yl, 1-cyano-2-methylprop-3-yl, 1-cyano-3-methylprop-3-yl, 1-cyano-2,3-dimethylprop-3-yl, 1-hydroxyeth-2-yl, 1-hydroxy-1-methyleth-2-yl, 1-hydroxy-2-methyleth-2-yl, 1-hydroxy-1,2-dimethyleth-2-yl, 1-hydroxy-2,2-dimethyleth-2-yl, 1-hydroxyprop-3-yl, 1-hydroxy-1-methylprop-3-yl, 1-hydroxy-2-methylprop-3-yl, 1-hydroxy-3-methylprop-3-yl, 1-hydroxy-2,3-dimethylprop-3-yl and (C 3 -C 7 )-cycloalkyl may be substituted by 1 or 2 fluorine substituents,
and
in which (C 3 -C 7 )-cycloalkyl may be substituted by a substituent selected from the group of hydroxy and cyano,
and
in which phenyl may be substituted by 1 or 2 substituents independently of one another selected from the group of fluorine, chlorine, cyano and methyl,
R 11 is methyl or ethyl,
and salts thereof.
20 . The method of claim 17 , wherein in the compound of formula (I)
A is —S(═O) 2 —, R 1 is methyl, R 2 is hydrogen or fluorine, R 3 is hydrogen or fluorine, R 4 is hydrogen, R 5 is a group of the formula
where
# is the point of attachment to the indole,
and
R 9 is a group of the formula
in which
* is the point of attachment to —CR 10 R 11 ,
R 12 is fluorine, chlorine, methyl and trifluoromethyl,
R 13 is hydrogen, fluorine or chlorine,
R 14 is hydrogen, fluorine or chlorine,
R 15 is hydrogen, fluorine or chlorine,
with the proviso that at least one of the radicals R 13 , R 14 and R 15 is hydrogen,
R 10 is cyclopropyl,
in which cyclopropyl may be substituted by 1 or 2 fluorine substituents,
and
in which cyclopropyl may be substituted by a cyano substituent,
R 11 is methyl,
and salts thereof.
21 . The method of claim 17 , wherein in the compound of formula (I)
A is —S(═O) 2 —, R 1 is methyl or ethyl, R 2 is hydrogen or fluorine, R 3 is hydrogen or fluorine, R 4 is hydrogen, R 5 is a group of the formula
where
# is the point of attachment to the indole,
and
D is —CH 2 —,
R 6 is methyl, ethyl or cyclopropyl,
R 7 is hydrogen, fluorine, chlorine or methyl,
R 8 is hydrogen, fluorine or chlorine,
and salts thereof.
22 . The method of claim 17 , wherein in the compound of formula (I):
A is —S(═O) 2 —, R 1 is methyl, R 2 is hydrogen or fluorine, R 3 is hydrogen or fluorine, R 4 is hydrogen, R 5 is a group of the formula
where
# is the point of attachment to the indole,
and
R 9 is a group of the formula
in which
* is the point of attachment to —CR 10 R 11 ,
R 12 is fluorine, chlorine, methyl and trifluoromethyl,
R 13 is hydrogen, fluorine or chlorine,
R 14 is hydrogen, fluorine or chlorine,
R 15 is hydrogen, fluorine or chlorine,
with the proviso that at least one of the radicals R 13 , R 14 and R 15 is hydrogen,
R 10 is 1-cyanoeth-2-yl, 1-cyano-2-methyleth-2-yl or 1-cyanoprop-3-yl,
R 11 is methyl or ethyl,
and salts thereof.
23 . The method of claim 17 , wherein in the compound of formula (I):
A is —S(═O) 2 —, R 1 is methyl, R 2 is hydrogen or fluorine, R 3 is hydrogen or fluorine, R 4 is hydrogen, R 5 is a group of the formula
where
# is the point of attachment to the indole,
and
R 9 is a group of the formula
in which
* is the point of attachment to —CR 10 R 11 ,
R 12 is fluorine, chlorine, methyl and trifluoromethyl,
R 13 is hydrogen, fluorine or chlorine,
R 14 is hydrogen, fluorine or chlorine,
R 15 is hydrogen, fluorine or chlorine,
with the proviso that at least one of the radicals R 13 , R 14 and R 15 is hydrogen,
R 10 is a group of the formula
in which
## is the point of attachment to —CR 9 R 11 ,
R 16 is fluorine or chlorine,
R 11 is hydrogen,
and salts thereof.
24 . The method of claim 17 , wherein in the compound of formula (I):
A is —S(═O) 2 —, R 1 is methyl, R 2 is hydrogen or fluorine, R 3 is hydrogen or fluorine, R 4 is hydrogen, R 5 is a group of the formula
where
# is the point of attachment to the indole,
and
R 9 is phenyl or benzothienyl,
in which phenyl and benzothienyl may be substituted by 1 or 2 substituents independently of one another selected from the group of fluorine, chlorine, methyl and trifluoromethyl,
R 10 is 1-cyanoeth-2-yl, 1-cyano-2-methyleth-2-yl or 1-cyanoprop-3-yl,
R 11 is hydrogen,
and salts thereof.
25 . The method of claim 17 , wherein in the compound of formula (I):
A is —S(═O) 2 —, R 1 is methyl, R 2 is hydrogen or fluorine, R 3 is hydrogen or fluorine, R 4 is hydrogen, R 5 is a group of the formula
where
# is the point of attachment to the indole,
and
R 9 is a group of the formula
in which
* is the point of attachment to —CR 10 R 11 ,
R 12 is fluorine, chlorine, methyl and trifluoromethyl,
R 13 is hydrogen, fluorine or chlorine,
R 14 is hydrogen, fluorine or chlorine,
R 15 is hydrogen, fluorine or chlorine,
with the proviso that at least one of the radicals R 13 , R 14 and R 15 is hydrogen,
R 10 is cyclopropyl,
in which cyclopropyl may be substituted by a cyano substituent,
or
in which cyclopropyl may be substituted by 1 or 2 fluorine substituents,
R 11 is hydrogen,
and salts thereof.
26 . The method of claim 17 , wherein the compound of formula (I) is a compound of formula (II):
27 . The method of claim 17 , wherein the compound of formula (I) is administered in combination with at least one active ingredient selected from the group consisting of ACE inhibitors, rennin inhibitors, angiotensin II receptor antagonists, beta-blockers, acetylsalicylic acid, diuretics, calcium antagonists, statins, digitalis (digoxin) derivatives, vasopressin antagonists, adenosine Al antagonists, calcium sensitizers, nitrates, and antithrombotics.Join the waitlist — get patent alerts
Track US2011201564A1 — get alerts on status changes and closely related new filings.
We store only your email — no account needed. See our privacy policy.