Carboxamide compounds and their use as antagonists of a human 11cby receptor

• US 20040063686A1
• Filed: 09/30/2003
• Published: 04/01/2004
• Est. Priority Date: 07/31/2000
• Status: Abandoned Application

• Current Assignee: Christopher Norbert Johnson, David Witty, Geoffrey Stemp, Kevin Michael Thewlis, Martin Jones, Oʼtoole, Catherine Anne
• Original Assignee: Christopher Norbert Johnson, David Witty, Geoffrey Stemp, Kevin Michael Thewlis, Martin Jones, Oʼtoole, Catherine Anne
• Inventors: OʼToole, Catherine Anne, Johnson, Christopher Norbert, Stemp, Geoffrey, Jones, Martin, Thewlis, Kevin Michael, Witty, David
• Application Number:
  US10/343,424
• Publication Number:
  US 20040063686A1
• Time in Patent Office: Days
• US Class Current: 514/211.15
• CPC Class Codes: A61K 31/165 having aromatic rings, e.g. colchicine, atenolol, progabide
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/395 having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07C 233/75 with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 235/42 having carbon atoms of carboxamide groups bound to carbon atoms of six-membered aromatic rings and singly-bound oxygen atoms bound to the same carbon skeleton
• CPC Class Codes: C07C 235/48 having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by singly-bound oxygen atoms
• CPC Class Codes: C07C 235/84 with the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 237/40 having the nitrogen atom of the carboxamide group bound to a carbon atom of a six-membered aromatic ring
• CPC Class Codes: C07C 255/57 containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
• CPC Class Codes: C07C 2601/14 The ring being saturated
• CPC Class Codes: C07C 317/44 having sulfone or sulfoxide groups and carboxyl groups bound to the same carbon skeleton
• CPC Class Codes: C07C 323/62 having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
• CPC Class Codes: C07D 207/08 with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms
• CPC Class Codes: C07D 211/42 attached in position 3 or 5
• CPC Class Codes: C07D 213/56 Amides
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 241/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 271/06 1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
• CPC Class Codes: C07D 271/10 : 1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
• CPC Class Codes: C07D 295/088 : to an acyclic saturated chain
• CPC Class Codes: C07D 295/135 : with the ring nitrogen atoms and the substituent nitrogen atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 295/155 : with the ring nitrogen atoms and the carbon atoms with three bonds to hetero atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
• CPC Class Codes: C07D 317/60 : Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
• CPC Class Codes: C07D 333/24 : Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals

Abstract

Compounds of formula (I) in which: each A is independently hydrogen, C1-6alkyl optionally substituted by hydroxyl, C1-6alkoxy, C1-6alkenyl or C1-6acyl group or a halogen atom or hydroxyl, CN or CF3 group; R3 is hydrogen, methyl or ethyl; R4 is an optionally substituted aromatic carbocyclic or heterocyclic ring; Z is an O or S atom, or an NH or CH2 group, or a single bond, at the 3 or 4 position of R4 relative to the carbonyl group; R5 is an optionally substituted aromatic carbocyclic or heterocyclic ring, or an optionally substituted, saturated or unsaturated, carbocyclic or heterocyclic ring; and Q is (a) Where X, Y, R1 and R2 are as defined in claim 1; are antagonists of a human 11CBy receptor.

Claims

1. A method of treating the Disorders which comprises administering to a mammal suffering from one or more of the Disorders an effective amount of a compound of formula (I), or a pharmaceutically acceptable salt or solvate thereof, in which:

2. A compound of formula (I) as defined in claim 1, or a salt or solvate thereof, in which R3 is methyl or ethyl.

3. A compound according to claim 2, which is any one of the compounds set out in Table E herein.

4. A compound of formula (I) as defined in claim 1 or a salt or solvate thereof, excluding the compounds:

N-[4-[2-[bis(1-methylethyl)anmino]ethoxy]-2-fluorophenyl]-[1,1′

-biphenyl]-4-carboxamide,

N-[4-[2-[bis(1-methylethyl)amino]ethoxy]phenyl]-[1,1′

-biphenyl]-4-carboxamide, biphenyl-4-carboxylic acid [4-(2-diisopropylamino-ethoxy)-phenyl]-amide,

N-[4-(2-diisopropylamino-ethoxy)-phenyl]-4-phenoxy-benzamide,

N-[4-(2-diethylamino-ethoxy)-phenyl]-4-phenoxy-benzamide,

N-[4-(2-diisopropylamino-ethoxy)-phenyl]-3-phenoxy-benzamide

N-[4-(2-diethylamino-ethoxy)-phenyl]-3-phenoxy-benzamide,

4-cyclohexyl-N-[4-(2-diisopropylamino-ethoxy)-phenyl]-benzamide,

4-cyclohexyl-N-[4-(2-diethylamino-ethoxy)-phenyl]-benzamide,

4-benzyl-N-[4-(2-diisopropylamino-ethoxy)-phenyl]-benzamide,

4-benzyl-N-[4-(2-diethylamino-ethoxy)-phenyl]-benzamide,

4′

-ethyl-biphenyl-4-carboxylic acid [4-(2-diisopropylamino-ethoxy)-phenyl]-amide,

and 4′

-ethyl-biphenyl-4-carboxylic acid [4-(2-diethylamino-ethoxy)-phenyl]-amide.

5. A process for the preparation of a compound of formula (I), or a salt or solvate thereof, as defined in claim 2, which process comprises the reaction of a compound of formula (X)

R5-Z-R4-COL 

 

(X)

where R5, Z, and R4 are as defined for formula (I) in claim 1, and L is a leaving group with a compound of formula (XI)

6. A process for the preparation of a compound of formula (I), or a salt or solvate thereof, as defined in claim 1, which process comprises the reaction of a compound of formula (X) wherein R5, Z, and R4 are as defined for formula (I) in claim 1 with a compound of formula (XI) wherein Q, A, and R3 are as defined in claim 1, with the proviso that a process for the preparation of:

N-[4-[2-[bis(1-methylethyl)amino]ethoxy]-2-fluorophenyl]-[1,1′

-biphenyl]-4-carboxamide,

N-[4-[2-[bis(1-methylethyl)amino]ethoxy]phenyl]-[1,1′

-biphenyl]4-carboxamide, biphenyl-4-carboxylic acid [4-(2-diisopropylamino-ethoxy)-phenyl]-amide,

N-[4-(2-diisopropylamino-ethoxy)-phenyl]-4-phenoxy-benzamide,

N-[4-(2-diethylamino-ethoxy)-phenyl]-4-phenoxy-benzamide,

N-[4-(2-diisopropylamino-ethoxy)-phenyl]-3-phenoxy-benzamide,

N-[4-(2-diethylamino-ethoxy)-phenyl]-3-phenoxy-benzamide,

4-cyclohexyl-N-[4-(2-diisopropylamino-ethoxy)-phenyl]-benzamide,

4-cyclohexyl-N-[4-(2-diethylamino-ethoxy)-phenyl]-benzamide,

4-benzyl-N-[4-(2-diisopropylamino-ethoxy)-phenyl]-benzamide,

4-benzyl-N-[4-(2-diethylamino-ethoxy)-phenyl]-benzamide,

4′

-ethyl-biphenyl-4-carboxylic acid [4-(2-diisopropylamino-ethoxy)-phenyl]-amide,

and 4′

-ethyl-biphenyl-4-carboxylic acid [4-(2-diethylamino-ethoxy)-phenyl]-amide is excluded.

7. A pharmaceutical composition for use in the treatment and/or prophylaxis of one or more of the Disorders which comprises a compound of this invention, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

8. A method of treatment and/or prophylaxis of one or more of the Disorders comprising administering to the sufferer in need thereof an effective or prophylactic amount of a compound of this invention, or a pharmaceutically acceptable salt or solvate thereof.

9. Use of a compound of this invention, or a pharmaceutically acceptable salt or solvate thereof, for the manufacture of a medicament for the treatment and/or prophylaxis of one or more of the Disorders.

10. Use of a novel compound of this invention, or a pharmaceutically acceptable salt or solvate, thereof as a therapeutic agent, in particular for the treatment and/or prophylaxis of one or more of the Disorders.

11. A method for the treatment of diabetes, major depression, manic depression, anxiety, schizophrenia and sleep disorders, in human or non-human mammals which method comprises the administration of a therapeutically effective amount of an antagonist to the human 11CBy receptor.