US 6,458,781 B1Granted

Substituted diarylalkyl amides as calcium channel antagonists

OwnerDavid Thomas Connor, Lain-Yen Hu +6inventors

InventorsDavid Thomas Connor, Lain-Yen Hu, Thomas Charles Malone, Michael Francis Rafferty, Bruce David Roth, Todd Robert Ryder, Anthony Denver Sercel, Yuntao Song

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Abstract

The present invention provides compounds that block calcium channels and have the Formula I: The present invention also provides pharmaceutical compositions containing the compounds of Formula I and methods of using them to treat stroke, cerebral ischemia, head trauma, and epilepsy.

Claims20

Dependent claims

A compound having the structural Formula I

or the pharmaceutically acceptable salts, thereof, wherein
X is —NH(CH2)3—;
each R1 and R2 are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl,
—(CH2)nphenyl, —(CH2)nsubstituted phenyl wherein the substituents on the phenyl group are selected from the group consisting of halogen, C1-C8 alkyl, —CN, —CF3, —NO2, —NH2, —NHC1-C8 alkyl, —N(C1-C8 alkyl)2, —OC1-C8 alkyl, and —OH,
—C3-C7 cycloalkyl-(CH2)n—, C3-C7 heterocycle-(CH2)n— wherein one of C3-C7 is replaced with a heteroatom selected from the group consisting of N, O, or S and wherein the heterocycle is saturated or unsaturated, monocyclic or bicyclic,
R1 and R2 together with the nitrogen atom to which they are both attached form a heterocycloalkyl group selected from piperidinyl and morpholinyl, with the proviso that R1 and R2 cannot simultaneously be hydrogen;
n is 0 to 6
R3 is hydrogen, C1-C6 alkyl, phenyl, substituted phenyl selected from the substituents consisting of halogen, C1-C8 alkyl, —CN, —CF3, —NO2, —NH2, —NHC1-C8 alkyl, —N(C1-C8 alkyl)2, —OC1-C8 alkyl, and —OH, benzyl, substituted benzyl selected from the substituents consisting of halogen, C1-C8 alkyl, —CN, —CF3, —NO2, —NH2, —NHC1-C8 alkyl, —N(C1-C8 alkyl)2, —OC1-C8 alkyl and —OH, or —(CH2)n—C3-C7 cycloalkyl;
R4 is hydrogen or C1-C6 alkyl, with the proviso that R3 and R4 cannot simultaneously be hydrogen;
or R3 and R4 together with the carbon atom to which they are attached form a C3-C7 cycloalkyl ring;
each R5 and R6 are substituted phenyl selected from the substituents consisting of halogen, C1-C8 alkyl, —CN, —CF3, —NO2, —NH2, —NHC1-C8 alkyl, —N(C1-C8 alkyl)2, —OC1-C8 alkyl, and —OH;
and
R7 is C1-C6 alkyl, phenyl, or C3-C7 heterocycloalkyl wherein one of C3-C7 is replaced with a heteroatom selected from the group consisting of N, O, or S and wherein the heterocycle is saturated or unsaturated, monocyclic or bicyclic.

10 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/403,579Filed 25 Oct 1999 · us provisional application
Priority: 27 Apr 1998
Granted: 1 Oct 2002
Term ends: Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07D 295/215
By radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof: radicals derived from nitrogen analogues of carbonic acid
C07C 211/29
Of an unsaturated carbon skeleton containing at least one six-membered aromatic ring: the carbon skeleton being further substituted by halogen…
C07C 237/06
The carbon skeleton being acyclic and saturated: having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon…
C07C 237/14
Having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton: the carbon skeleton being saturated and…

Family

Application60/083,141Us provisional application · filed 27 Apr 1998
US 6,458,781 B1This patent

From the US filing history. Foreign family members aren’t listed.

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Abstract

A compound having the structural Formula I

or the pharmaceutically acceptable salts, thereof, wherein
X is —NH(CH2)3—;
each R1 and R2 are independently hydrogen, C1-C6 alkyl, C2-C6 alkenyl,
—(CH2)nphenyl, —(CH2)nsubstituted phenyl wherein the substituents on the phenyl group are selected from the group consisting of halogen, C1-C8 alkyl, —CN, —CF3, —NO2, —NH2, —NHC1-C8 alkyl, —N(C1-C8 alkyl)2, —OC1-C8 alkyl, and —OH,
—C3-C7 cycloalkyl-(CH2)n—, C3-C7 heterocycle-(CH2)n— wherein one of C3-C7 is replaced with a heteroatom selected from the group consisting of N, O, or S and wherein the heterocycle is saturated or unsaturated, monocyclic or bicyclic,
R1 and R2 together with the nitrogen atom to which they are both attached form a heterocycloalkyl group selected from piperidinyl and morpholinyl, with the proviso that R1 and R2 cannot simultaneously be hydrogen;
n is 0 to 6
R3 is hydrogen, C1-C6 alkyl, phenyl, substituted phenyl selected from the substituents consisting of halogen, C1-C8 alkyl, —CN, —CF3, —NO2, —NH2, —NHC1-C8 alkyl, —N(C1-C8 alkyl)2, —OC1-C8 alkyl, and —OH, benzyl, substituted benzyl selected from the substituents consisting of halogen, C1-C8 alkyl, —CN, —CF3, —NO2, —NH2, —NHC1-C8 alkyl, —N(C1-C8 alkyl)2, —OC1-C8 alkyl and —OH, or —(CH2)n—C3-C7 cycloalkyl;
R4 is hydrogen or C1-C6 alkyl, with the proviso that R3 and R4 cannot simultaneously be hydrogen;
or R3 and R4 together with the carbon atom to which they are attached form a C3-C7 cycloalkyl ring;
each R5 and R6 are substituted phenyl selected from the substituents consisting of halogen, C1-C8 alkyl, —CN, —CF3, —NO2, —NH2, —NHC1-C8 alkyl, —N(C1-C8 alkyl)2, —OC1-C8 alkyl, and —OH;
and
R7 is C1-C6 alkyl, phenyl, or C3-C7 heterocycloalkyl wherein one of C3-C7 is replaced with a heteroatom selected from the group consisting of N, O, or S and wherein the heterocycle is saturated or unsaturated, monocyclic or bicyclic.

10 more elements

Facts

Application

09/403,579Filed 25 Oct 1999 · us provisional application

Priority

27 Apr 1998

Granted

1 Oct 2002

Term ends

Not estimatedThe source records don’t support an estimate.

Classification15 codes

C07D 295/215
By radicals derived from carbonic acid, or sulfur or nitrogen analogues thereof: radicals derived from nitrogen analogues of carbonic acid
C07C 211/29
Of an unsaturated carbon skeleton containing at least one six-membered aromatic ring: the carbon skeleton being further substituted by halogen…
C07C 237/06
The carbon skeleton being acyclic and saturated: having the nitrogen atoms of the carboxamide groups bound to hydrogen atoms or to acyclic carbon…
C07C 237/14
Having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton: the carbon skeleton being saturated and…