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US 6,211,365 B1Granted
Fused pyrrolecarboxamides; a new class of GABA brain receptor ligands
AssigneeNeurogen Corporation
InventorsPamela Albaugh, Gang Liu, Kenneth Shaw, Alan Hutchison
Life of this patent
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Abstract
Disclosed are compounds of the formula: or the pharmaceutically acceptable non-toxic salts thereof wherein: G, X, T, n, and R3-R6 are as defined herein, which compounds are highly selective agonists, antagonists or inverse agonists for GABAa brain receptors or prodrugs of agonists, antagonists or inverse agonists for GABAa brain receptors. These compounds are useful in the diagnosis and treatment of anxiety, sleep and seizure disorders, overdose with benzodiazepine drugs and for enhancement of memory.
Claims10
A compound of the formula:
- or a pharmaceutically acceptable non-toxic salt thereof wherein:
- G represents
- where
- Q is phenyl optionally mono or disubstituted with hydroxy or halogen;
- T is halogen, hydrogen, hydroxyl, amino or alkoxy having 1-6 carbon atoms;
- W is oxygen, nitrogen, sulfur, or CR7R8 where R7 and R8 are the same or different and represent hydrogen, alkyl, or R7-R8 taken together represents a cyclic moiety having 3-7 carbon atoms;
- X is hydrogen, hydroxyl, or alkyl;
- Z represents a group of the formula:
- where Rz is hydrogen or C1-C6 alkyl;
- or
- a group of the formula:
- where
- s is 0, 1, 2 or 3, and the sum of s and m is not less than 1;
- Ro is a group of the formula:
- where Rz is as defined above;
- independently represent a carbon chain optionally substituted with hydrogen, halogen, or straight or branched chain lower alkyl having 1-6 carbon atoms;
- wherein
- k is 0, 1, 2, or 3;
- m is 0, 1, 2, or 3;
- and
- n is 0, 1, 2, or 3;
- R3, R4, R5, and R6 are the same or different and are selected from hydrogen, alkyl, —COR11, —CO2R11 where R11 is alkyl or cycloalkyl having 3-7 carbon atoms;
- and —CONR12R13 where R12 and R13 are selected independently from hydrogen, alkyl, cycloalkyl having 3-7 carbon atoms, phenyl, and 2-, 3-, or 4-pyridyl, or NR12R13 forms a heterocyclic group which is morpholinyl, piperidinyl, pyrrolidinyl, or N-alkyl piperazinyl;
- or
- R3-R4 may be taken together to form a cyclic moiety having 3-7 carbon atoms;
- or
- R5-R6 may be taken together to form a cyclic moiety having 3-7 carbon atoms;
- and
- where each alkyl group forming an R3, R4, R5, or R6 substituent or portion thereof may be substituted independently with hydroxy or mono- or dialkylamino where each alkyl is independently alkyl or cycloalkyl having 3-7 carbon atoms.
26 more elements
A compound of the formula:
- or the pharmaceutically acceptable non-toxic salt thereof wherein:
- Q is phenyl optionally mono or disubstituted with hydroxy or halogen;
- W is oxygen or nitrogen;
- Z represents a group of the formula:
- where each Rz is hydrogen or C1-C6 alkyl;
- a group of the formula:
- where
- s is 0, 1, 2 or 3, and the sum of s and m is not less than 1;
- Ro is a group of the formula:
- where Rz is as defined above;
- independently represent a carbon chain optionally substituted with hydrogen, halogen, or straight or branched chain lower alkyl having 1-6 carbon atoms;
- wherein
- k is 0, 1, 2, or 3;
- m is 0, 1, 2, or 3;
- and
- n is 1 or 2;
- and
- R3, R4, R5, and R6 are the same or different and are selected from hydrogen, alkyl, —COR11, —CO2R11 where R11 is alkyl or cycloalkyl having 3-7 carbon atoms;
- and —CONR12R13 where R12 and R13 are selected independently from hydrogen, alkyl, cycloalkyl having 3-7 carbon atoms, phenyl, and 2-, 3-, or 4-pyridyl, or NR12R13 forms a heterocyclic group which is morpholinyl, piperidinyl, pyrrolidinyl, or N-alkyl piperazinyl;
- or
- R3-R4 may be taken together to form a cyclic moiety having 3-7 carbon atoms;
- or
- R5-R6 may be taken together to form a cyclic moiety having 3-7 carbon atoms;
- and
- where each alkyl group forming an R3, R4, R5, or R6 substituent or portion thereof may be substituted independently with hydroxy or mono- or dialkylamino where each alkyl is independently alkyl or cycloalkyl having 3-7 carbon atoms.
22 more elements
A compound of formula A or formula B:
- or a pharmaceutically acceptable salt thereof wherein
- R3, R4, R5, and R6 are the same or different and are selected from hydrogen, alkyl, —COR11, —CO2R11 where R11 is alkyl or cycloalkyl having 3-7 carbon atoms;
- and —CONR12R13 where R12 and R13 are selected independently from hydrogen, alkyl, cycloalkyl having 3-7 carbon atoms, phenyl, and 2-, 3-, or 4-pyridyl, or NR12R13 forms a heterocyclic group which is morpholinyl, piperidinyl, pyrrolidinyl, or N-alkyl piperazinyl;
- or
- R3-R4 may be taken together to form a cyclic moiety having 3-7 carbon atoms;
- or
- R5-R6 may be taken together to form a cyclic moiety having 3-7 carbon atoms;
- and
- where each alkyl group forming an R3, R4, R5, or R6 substituent or portion thereof may be substituted independently with hydroxy or mono- or dialkylamino where each alkyl is independently alkyl or cycloalkyl having 3-7 carbon atoms.;
- and
- G represents
- where
- Rh is hydrogen, halogen, C1-C6alkyl, C1-C6alkoxy, or trifluoromethyl;
- s is 0, 1, 2 or 3, and the sum of s and m is not less than 1;
- Ro is a group of the formula:
- where Rz is hydrogen or C1-C6 alkyl.
13 more elements
Dependencies are inferred from the claim text.