US 2002/0002161 A1Published application

Novel 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indole compounds

AssigneePharmacia & Upjohn Company

InventorsMichael Dalton Ennis, Robert Louis Hoffman, Nabil B. Ghazal, Rebecca M. Olson

Life of this patent

Estimating the term…

Abstract

Certain 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indoles are 5-HT ligands and are useful for treating diseases wherein modulation of 5-HT activity is desired.

Claims27

Dependent claims

A compound of formula I:

218
where a is a single bond or double bond, and where
R1a, R1b, R2a and R2b are each independently
(a) H, Cl, Br, I, F, CN, CF3, OCF3, OR5, CONR5R6, COR5, CO2R5, Y(CH2)mXR5 or YC(O)(CH2)mXR5, where m=0-3, Y=CH2, S, O, or NR6, X=CH2, S, O, NR6;
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(c) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR7, OR7, NR7R8, SR7, CO2R7, CONR7R8 or NR7COR8;
and where
R3 is
(a) H, Cl, Br, I, F, CN, CF3, OCF3, alkyl, Ar, OR5, SR5, CHO, CONR5R6, COR5, CO2R5, (Y)o(CH2)nXR5, C(O)C(O)XR5, (Y)o(CH2)nC(O)XR5, C(O)(CH2)nXR5, (Y)o(CH2)nN(R6)C(O)R5, (Y)o(CH2)nN(R6)S(O)2R5, (Y)o(CH2)nN(R6)C(O)OR5, (Y)o(CH2)nN(R6)C(O)NR5R6 where o=0 or 1, n=0-3, X=CH2, S, O, or NR6 and Y=CH2, S, O or NR6, where Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(b) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R8, SR10, CO2R10, CONR10R8 or NR10COR8;
and where
R4, R5 and R6 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups other than H may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11 or NR10COR11;
or where R5 and R6 are linked to form a 3 to 8 member ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
and where
R7, R8, and R9 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl groups, wherein any of these groups other than H may be optionally substituted with halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11, NR10COR11, NR10CONR11R12, or where R7, R8, or R9 are linked to form a ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR10, CF3, OCF3, SR10, SO2R10, SO2NR10R11, NR10R11, CONR10R11, NR10COR11, NR10CONR11R12, CO2R10, COR10, or R10;
and where
R10, R11 and R12 are each independently H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
or a stereoisomer or pharmaceutically acceptable salt thereof.

33 more elements

A compound of formula I:

219
where a is a single bond or double bond, and where
R1a, R1b, R2a and R2b are each independently
(a) H, Cl, Br, I, F, CN, CF3, OCF3, OR5, CONR5R6, COR5, CO2R5, Y(CH2)mXR5 or YC(O)(CH2)mXR5, where m=0-3, Y=CH2, S, O, or NR6, X=CH2, S, O, NR6;
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(c) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR7, OR7, NR7R8, SR7, CO2R7, CONR7R8 or NR7COR8;
and where
R3 is
(a) H, Cl, Br, I, F, CN, CF3, OCF3, alkyl, Ar, OR5, SR5, CHO, CONR5R6, COR5, CO2R5, (Y)o(CH2)nXR5, C(O)C(O)XR5, (Y)o(CH2)nC(O)XR5, C(O)(CH2)nXR5, (Y)o(CH2)nN(R6)C(O)R5, (Y)o(CH2)nN(R6)S (O)2R5, (Y)o(CH2)nN(R6)C(O)OR5, (Y)o(CH2)nN(R6)C(O)NR5R6 where o=0 or 1, n=0-3, X=CH2, S, O, or NR6 and Y=CH2, S, O or NR6, where Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(b) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R8, SR10, CO2R10, CONR10R8 or NR10COR8;
and where
R4, R5 and R6 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups other than H may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11 or NR10COR11;
or where R5 and R6 are linked to form a 3 to 8 member ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
and where
R7, R8, and R9 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl groups, wherein any of these groups other than H may be optionally substituted with halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11, NR10COR11, NR10CONR11R12, or where R7, R8, or R9 are linked to form a ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR10, CF3, OCF3, SR10, SO2R10, SO2NR10R11, NR10R11, CONR10R11, NR10COR11, NR10CONR11R12, CO2R10, COR10, or R10;
and where
R10, R11 and R12 are each independently H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
or a stereoisomer or pharmaceutically acceptable salt thereof.

33 more elements

A method for treating a disease or disorder of the central nervous system in a mammal comprising administering to said mammal a pharmaceutically effective amount of

A compound of formula I:
220
where a is a single bond or double bond, and where
R1a, R1b, R2a and R2b are each independently
(a) H, Cl, Br, I, F, CN, CF3, OCF3, OR5, CONR5R6, COR5, CO2R5, Y(CH2)mXR5 or YC(O)(CH2)mXR5, where m=0-3, Y=CH2, S, O, or NR6, X=CH2, S, O, NR6;
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(c) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR7, OR7, NR7R8, SR7, CO2R7, CONR7R8 or NR7COR8;
and where
R3 is
(a) H, Cl, Br, I, F, CN, CF3, OCF3, alkyl, Ar, OR5, SR5, CHO, CONR5R6, COR5, CO2R5, (Y)o(CH2)nXR5, C(O)C(O)XR5, (Y)o(CH2)nC(O)XR5, C(O)(CH2)nXR5, (Y)o(CH2)nN(R6)C(O)R5, (Y)o(CH2)nN(R6)S(O)2R5, (Y)o(CH2)nN(R6)C(O)OR5, (Y)o(CH2)nN(R6)C(O)NR5R6 where o=0 or 1, n=0-3, X=CH2, S, O, or NR6 and Y=CH2, S, O or NR6, where Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(b) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R8, SR10, CO2R10, CONR10R8 or NR10COR8;
and where
R4, R5 and R6 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups other than H may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11 or NR10COR11;
or where R5 and R6 are linked to form a 3 to 8 member ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
and where
R7, R8, and R9 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl groups, wherein any of these groups other than H may be optionally substituted with halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11, NR10COR11, NR10CONR11R12, or where R7, R8, or R9 are linked to form a ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR10, CF3, OCF3, SR10, SO2R10, SO2NR10R11, NR10R11, CONR10R11, NR10COR11, NR10CONR11R12, CO2R10, COR10, or R10;
and where
R10, R11 and R12 are each independently H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
or a stereoisomer or pharmaceutically acceptable salt thereof.

34 more elements

A method for modulating 5-HT receptor function, comprising contacting the receptor with an effective inhibitory amount of a compound of a compound of formula I:

221
where a is a single bond or double bond, and where
R1a, R1b, R2a and R2b are each independently
(a) H, Cl, Br, I, F, CN, CF3, OCF3, OR5, CONR5R6, COR5, CO2R5, Y(CH2)mXR5 or YC(O)(CH2)mXR5, where m=0-3, Y=CH2, S, O, or NR6, X=CH2, S, O, NR6;
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(c) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR7, OR7, NR7R8, SR7, CO2R7, CONR7R8 or NR7COR8;
and where
R3 is
(a) H, Cl, Br, I, F, CN, CF3, OCF3, alkyl, Ar, OR5, SR5, CHO, CONR5R6, COR5, CO2R5, (Y)o(CH2)nXR5, C(O)C(O)XR5, (Y)o(CH2)nC(O)XR5, C(O)(CH2)nXR5, (Y)o(CH2)nN(R6)C(O)R5, (Y)o(CH2)nN(R6)S(O)2R5, (Y)o(CH2)nN(R6)C(O)OR5, (Y)o(CH2)nN(R6)C(O)NR5R6 where o=0 or 1, n=0-3, X=CH2, S, O, or NR6 and Y=CH2, S, O or NR6, where Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(b) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R8, SR10, CO2R10, CONR10R8 or NR10COR8;
and where
R4, R5 and R6 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups other than H may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11 or NR10COR11;
or where R5 and R6 are linked to form a 3 to 8 member ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
and where
R7, R8, and R9 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl groups, wherein any of these groups other than H may be optionally substituted with halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11, NR10COR11, NR10CONR11R12, or where R7, R8, or R9 are linked to form a ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR10, CF3, OCF3, SR10, SO2R10, SO2NR10R11, NR10R11, CONR10R11, NR10COR11, NR10CONR11R12, CO2R10, COR10, or R10;
and where
R10, R11 and R12 are each independently H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
or a stereoisomer or pharmaceutically acceptable salt thereof.

33 more elements

The use of a compound of formula I:

222
where a is a single bond or double bond, and where
R1a, R1b, R2a and R2b are each independently
(a) H, Cl, Br, I, F, CN, CF3, OCF3, OR5, CONR5R6, COR5, CO2R5, Y(CH2)mXR5 or YC(O)(CH2)mXR5, where m=0-3, Y=CH2, S, O, or NR6, X=CH2, S, O, NR6;
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(c) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR7, OR7, NR7R8, SR7, CO2R7, CONR7R8 or NR7COR8;
and where
R3 is
(a) H, Cl, Br, I, F, CN, CF3, OCF3, alkyl, Ar, OR5, SR5, CHO, CONR5R6, COR5, CO2R5, (Y)o(CH2)nXR5, C(O)C(O)XR5, (Y)o(CH2)nC(O)XR5, C(O)(CH2)nXR5, (Y)o(CH2)nN(R6)C(O)R5, (Y)o(CH2)nN(R6)S(O)2R5, (Y)o(CH2)nN(R6)C(O)OR5, (Y)o(CH2)nN(R6)C(O)NR5R6 where o=0 or 1, n 0-3, X=CH2, S, O, or NR6 and Y=CH2, S, O or NR6, where Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(b) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R8, SR10, CO2R10, CONR10R8 or NR10COR8;
and where
R4, R5 and R6 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups other than H may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11 or NR10COR11;
or where R5 and R6 are linked to form a 3 to 8 member ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
and where
R7, R8, and R9 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl groups, wherein any of these groups other than H may be optionally substituted with halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11, NR10COR11, NR10CONR11R12, or where R7, R8, or R9 are linked to form a ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR10, CF3, OCF3, SR10, SO2R10, SO2NR10R11, NR10R11, CONR10R11, NR10COR11, NR10CONR11R12, CO2R10, COR10, or R10;
and where
R10, R11 and R12 are each independently H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
or a stereoisomer or pharmaceutically acceptable salt thereof;
to prepare a medicament for treating or preventing diseases or disorders of the central nervous system.

34 more elements

A substance or a compound of formula I:

223
where a is a single bond or double bond, and where
R1a, R1b, R2a and R2b are each independently
(a) H, Cl, Br, I, F, CN, CF3, OCF3, OR5, CONR5R6, COR5, CO2R5, Y(CH2)mXR5 or YC(O)(CH2)mXR5, where m=0-3, Y=CH2, S, O, or NR6, X=CH2, S, O, NR6;
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(c) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR7, OR7, NR7R8, SR7, CO2R7, CONR7R8 or NR7COR8;
and where
R3 is
(a) H, Cl, Br, I, F, CN, CF3, OCF3, alkyl, Ar, OR5, SR5, CHO, CONR5R6, COR5, CO2R5, (Y)o(CH2)nXR5, C(O)C(O)XR5, (Y)o(CH2)nC(O)XR5, C(O)(CH2)nXR5, (Y)o(CH2)nN(R6)C(O)R5, (Y)o(CH2)nN(R6)S(O)2R5, (Y)o(CH2)nN(R6)C(O)OR5, (Y)o(CH2)nN(R6)C(O)NR5R6 where o=0 or 1, n=0-3, X=CH2, S, O, or NR6 and Y=CH2, S, O or NR6, where Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(b) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R8, SR10, CO2R10, CONR10R8 or NR10COR8;
and where
R4, R5 and R6 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups other than H may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11 or NR10COR11;
or where R5 and R6 are linked to form a 3 to 8 member ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
and where
R7, R8, and R9 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl groups, wherein any of these groups other than H may be optionally substituted with halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11, NR10COR11, NR10CONR11R12, or where R7, R8, or R9 are linked to form a ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR10, CF3, OCF3, SR10, SO2R10, SO2NR10R11, NR10R11, CONR10R11, NR10COR11, NR10CONR11R12, CO2R10, COR10, or R10;
and where
R10, R11 and R12 are each independently H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
or a stereoisomer or pharmaceutically acceptable salt thereof;
for use as a medicament.

34 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/803,242Filed 8 Mar 2001
Priority: 14 Mar 2000
Published: 3 Jan 2002
Term ends: Not estimatedThe source records don’t support an estimate.

Classification24 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 9/12
Drugs for disorders of the cardiovascular system: antihypertensives

Family

Application60/189,103Us provisional application · filed 14 Mar 2000
US 6,734,301 B2Related patent
US 2002/0002161 A1This patent

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

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Abstract

Certain 2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,7-a]indoles are 5-HT ligands and are useful for treating diseases wherein modulation of 5-HT activity is desired.

A compound of formula I:

218
where a is a single bond or double bond, and where
R1a, R1b, R2a and R2b are each independently
(a) H, Cl, Br, I, F, CN, CF3, OCF3, OR5, CONR5R6, COR5, CO2R5, Y(CH2)mXR5 or YC(O)(CH2)mXR5, where m=0-3, Y=CH2, S, O, or NR6, X=CH2, S, O, NR6;
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(c) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR7, OR7, NR7R8, SR7, CO2R7, CONR7R8 or NR7COR8;
and where
R3 is
(a) H, Cl, Br, I, F, CN, CF3, OCF3, alkyl, Ar, OR5, SR5, CHO, CONR5R6, COR5, CO2R5, (Y)o(CH2)nXR5, C(O)C(O)XR5, (Y)o(CH2)nC(O)XR5, C(O)(CH2)nXR5, (Y)o(CH2)nN(R6)C(O)R5, (Y)o(CH2)nN(R6)S(O)2R5, (Y)o(CH2)nN(R6)C(O)OR5, (Y)o(CH2)nN(R6)C(O)NR5R6 where o=0 or 1, n=0-3, X=CH2, S, O, or NR6 and Y=CH2, S, O or NR6, where Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
or
(b) linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R8, SR10, CO2R10, CONR10R8 or NR10COR8;
and where
R4, R5 and R6 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
wherein any of these groups other than H may be optionally substituted with one or more of the following:
halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11 or NR10COR11;
or where R5 and R6 are linked to form a 3 to 8 member ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR7, CF3, OCF3, SR7, SO2R7, SO2NR7R8, NR7R8, CONR7R8, NR7COR8, NR7CONR8R9, CO2R7, COR7, or R7;
and where
R7, R8, and R9 are each independently
(a) H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl groups, wherein any of these groups other than H may be optionally substituted with halogen, CN, NO2, COR10, OR10, NR10R11, SR10, CO2R10, CONR10R11, NR10COR11, NR10CONR11R12, or where R7, R8, or R9 are linked to form a ring;
or
(b) (CH2)pAr where p=0-3 and Ar is aryl or heteroaryl optionally substituted with one or more of the following:
H, halogen, CN, NO2, OR10, CF3, OCF3, SR10, SO2R10, SO2NR10R11, NR10R11, CONR10R11, NR10COR11, NR10CONR11R12, CO2R10, COR10, or R10;
and where
R10, R11 and R12 are each independently H, linear or branched C1-C8 alkyl, linear or branched C2-C8 alkenyl, linear or branched C2-C8 alkynyl, C3-C8 cycloalkyl, C3-C8 cycloalkenyl, or C3-C8 cycloalkynyl;
or a stereoisomer or pharmaceutically acceptable salt thereof.

33 more elements

Facts

Application

09/803,242Filed 8 Mar 2001

Priority

14 Mar 2000

Published

3 Jan 2002

Term ends

Not estimatedThe source records don’t support an estimate.

Classification24 codes

C07D 487/04
In which the condensed system contains two hetero rings: ortho-condensed systems
A61P 1/08
Drugs for disorders of the alimentary tract or the digestive system: for nausea, cinetosis or vertigo; Antiemetics
A61P 3/04
Drugs for disorders of the metabolism: anorexiants; Antiobesity agents
A61P 9/12
Drugs for disorders of the cardiovascular system: antihypertensives