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US 2006/0142296 A1Published application
4(Phenyl-piperazinyl-methyl) benzamide derivatives and their use for the treatment of pain or gastrointestinal disorders
AssigneeAstraZeneca AB
InventorsWilliam Brown, Andrew Griffin
Life of this patent
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Abstract
Compounds of general formula:[Chemical formula should be inserted here. Please see paper copy] wherein R1, R2, and R3 are as defined in the specification, as well as salts, enantiomers thereof and pharmaceutical compositions including the compounds are prepared. They are useful in therapy, in particular in the management of pain.
Claims20
A compound of formula I, a pharmaceutically acceptable salt thereof:
- wherein
- R1 is selected from C3-6alkyl, C6-10aryl, C2-9heteroaryl, C6-10aryl-C1-4alkyl, C2-9heteroaryl-C1-4alkyl, C3-10cycloalkyl, C3-10cycloalkyl-C1-4alkyl, R8—C(═O)—, R8—S(═O)2—, R8—S(═O)—, R8—NHC(═O)—, R8—C(═S)— and R8—NH—C(═S)—, wherein R8 is selected from C3-6alkyl, C6-10aryl, C2-9heteroaryl, C6-10aryl-C1-4alkyl, C2-9heteroaryl-C1-4alkyl, C3-10cycloalkyl, and C3-10cycloalkyl-C1-4alkyl, wherein said C3-6alkyl, C60aryl, C2-9heteroaryl, C6-10aryl-C1-4alkyl, C2-9heteroaryl-C1-4alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl used in defining R1 and R8 are optionally substituted with one or more groups selected from —R, —NO2, —OR, —Cl, —Br, —I, —F, —CF3, —C(═O)R, —C(═O)OH, —NH2, —SH, —NHR, —NR2, —SR, —SO3H, —SO2R, —S(═O)R, —CN, —OH, —C(═O)OR, —C(═O)NR2, —NRC(═O)R, and —NRC(═O)—OR, wherein R is, independently, selected from —H, C1-6alkyl and phenyl;
- R2 is selected from —H and C1-6alkyl optionally substituted with one or more groups selected from halogen, —CF3, —OH, C1-3alkoxy, and halogen;
- and
- R3 is selected from —H, C1-6alkyl-O—C(═O)—, C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl, wherein said C1-6alkyl-O—C(═O)—, C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl are optionally substituted with one or more groups selected from C1-6alkyl, halogenated C1-6alkyl, —NO2, —CF3, C1-6alkoxy and halogen.
2 more elements
11-12. (canceled)
A process for preparing a compound of formula II, comprising:
- a) reacting a compound of formula III:
- with a compound of formula IV
- in the presence of a base having a pKa of more than 15
- wherein
- X is a halogen.
2 more elements
A process for preparing a compound of formula VI:
- comprising:
- reacting a compound of formula II
- with a compound of formula VII
- in the presence of SOX2 to form the compound of formula VI,
- wherein
- R3 is selected from —H, C1-6alkyl-O—C(═O)—, C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl, wherein said C1-6alkyl-O—C(═O)—, C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl are optionally substituted with one or more groups selected from C1-6alkyl, halogenated C1-6alkyl, —NO2, —CF3, C1-6alkoxy and halogen;
- and
- X is halogen.
5 more elements
A process for preparing a compound of formula I,
- comprising:
- reacting a compound of formula VIII,
- with R9—CHO in the presence of a reducing agent to form the compound of formula I:
- wherein
- R1 is R9—CH2—, wherein R9 is selected from phenyl, pyridyl, thienyl, furyl, imidazolyl, triazolyl, pyrrolyl, thiazolyl, N-oxido-pyridyl, benzyl, pyridylmethyl, thienylmethyl, furylmethyl, imidazolylmethyl, triazolylmethyl, pyrrolylmethyl, thiazolylmethyl and N-oxido-pyridylmethyl, optionally substituted with one or more groups selected from C1-4alkyl, halogen, —CF3, —OH, C1-3alkoxy, phenoxy and halogen;
- R2 is —H;
- and
- R3 is selected from C1-6alkyl-O—C(═O)—, C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl, wherein said C1-6alkyl-O—C(═O)—, C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl are optionally substituted with one or more groups selected from C1-6alkyl, halogenated C1-6alkyl, —NO2, —CF3, C1-6alkoxy and halogen.
5 more elements
A process for preparing a compound of formula IX,
- comprising:
- reacting a compound of formula VIII,
- with R8—Y—X or R8—Y—O—Y—R8 to form the compound of formula IX:
- wherein
- X is halogen;
- Y is selected from —C(═O)— and —S(═O)2—;
- R8 is selected from C3-6alkyl, C6-10aryl, C2-6heteroaryl, C6-10aryl-C1-4alkyl, C2-6heteroaryl-C1-4alkyl, C3-10cycloalkyl, and C3-10cycloalkyl-C1-4alkyl;
- wherein said C3-6alkyl, C6-10aryl, C2-6heteroaryl, C6-10aryl-C1-4alkyl, C2-6heteroaryl-C1-4alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl are optionally substituted with C1-4alkyl, halogen, —CF3, —OH, C1-3alkoxy, phenoxy, and halogen;
- and
- R3 is selected from C1-6alkyl-O—C(═O)—, C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl, wherein said C1-6alkyl-O—C(═O)—, C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl are optionally substituted with one or more groups selected from C1-6alkyl, halogenated C1-6alkyl, —NO2, —CF3, C1-6alkoxy and halogen.
7 more elements
A process for preparing a compound of formula IX,
- comprising:
- reacting a compound of formula VIII,
- with R8-Z to form the compound of formula IX:
- wherein
- Z is selected from —NCO and —NCS;
- Y is selected from —C(═O)NH— and —C(═S)NH—;
- R8 is selected from C3-6alkyl, C6-10aryl, C2-6heteroaryl, C6-10aryl-C1-4alkyl, C2-6heteroaryl-C1-4alkyl, C3-10cycloalkyl, and C3-10cycloalkyl-C1-4alkyl;
- wherein said C3-6alkyl, C6-10aryl, C2-6heteroaryl, C6-10aryl-C1-4alkyl, C2-6heteroaryl-C1-4alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl are optionally substituted with C1-4alkyl, halogen, —CF3, —OH, C1-3alkoxy, phenoxy, and halogen;
- and
- R3 is selected from C1-6alkyl-O—C(═O)—, C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl, wherein said C1-6alkyl-O—C(═O)—, C1-6alkyl, C3-6cycloalkyl, and C3-6cycloalkyl-C1-4alkyl are optionally substituted with one or more groups selected from C1-6alkyl, halogenated C1-6alkyl, —NO2, —CF3, C1-6alkoxy and halogen.
7 more elements
Dependencies are inferred from the claim text.