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US 8,133,892 B2Granted
Compounds that are useful for improving pharmacokinetics
AssigneeAbbott Laboratories
InventorDale J. Kempf
Life of this patent
Estimating the term…
Abstract
Novel compounds of formula 1 or a pharmaceutically acceptable salt thereof inhibit cytochrome P450 monooxygenase.
Claims18
A compound, prodrug of the compound, pharmaceutically acceptable salt of the compound or prodrug, or combination thereof, wherein:
- the compound corresponds in structure to formula I:
- R1 and R4 are each independently selected from the group consisting of furyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyrimidinyl, pyridazinyl, pyrrolyl, tetrazinyl, tetrazolyl, thiadiazolyl, thiazolyl, thienyl, triazinyl and triazolyl;
- R2 and R3 are each independently selected from the group consisting of hydrogen, alkenyl, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxyalkyl, alkynyl, arylalkoxyalkyl, arylalkoxycarbonyl, arylalkyl, arylalkylcarbonyl, arylcarbonyl, aryloxyalkyl, aryloxycarbonyl, arylthioalkoxyalkyl, arylthioalkyl, carboxyalkyl, cycloalkyl, cycloalkylalkyl, di(alkoxycarbonyl)alkyl, heteroarylalkoxyalkyl, heteroarylalkoxycarbonyl, heteroarylalkyl, heteroarylalkylcarbonyl, heteroarylcarbonyl, heteroaryloxyalkyl, heteroaryloxycarbonyl, heteroarylthioalkoxyalkyl, heteroarylthioalkyl, heterocyclealkoxyalkyl, heterocyclealkoxycarbonyl, heterocyclealkyl, heterocyclealkylcarbonyl, heterocyclecarbonyl, heterocycleoxyalkyl, heterocycleoxycarbonyl, heterocyclethioalkoxyalkyl, heterocyclethioalkyl, hydroxyalkyl, and (NRCRD)alkyl;
- R5 and R6 are each independently selected from the group consisting of hydrogen, lower alkyl, and arylalkyl;
- m is 0-3;
- n is 0-3;
- A1 is absent or selected from the group consisting of O and NRA1, wherein RA1 is selected from the group consisting of hydrogen and lower alkyl;
- A2 is absent or selected from the group consisting of O and NRA2, wherein RA2 is selected from the group consisting of hydrogen and lower alkyl;
- X1 and X2 are each independently selected from the group consisting of O and S;
- L is
- and
- p is 1 or 2;
- Rc and RD are each independently selected from the group consisting of hydrogen, alkoxycarbonyl, alkyl, alkylcarbonyl, alkylsulfonyl, arylalkoxycarbonyl, arylsulfonyl, formyl, (NRERF)carbonyl, and (NRERF)sulfonyl;
- RE and RF are each independently selected from the group consisting of hydrogen and lower alkyl;
- and
- wherein any one of the
- aryl,
- heteroaryl,
- heterocycle,
- cycloalkyl,
- cycloalkyl moiety of cycloalkylalkyl,
- aryl moieties of arylalkoxyalkyl, arylalkoxycarbonyl, arylalkyl, arylalkylcarbonyl, arylcarbonyl, aryloxyalkyl, aryloxycarbonyl, arylthioalkoxyalkyl, and arylthioalkyl,
- heteroaryl moieties of heteroarylalkoxyalkyl, heteroarylalkoxycarbonyl, heteroarylalkyl, heteroarylalkylcarbonyl, heteroarylcarbonyl, heteroaryloxyalkyl, heteroaryloxycarbonyl, heteroarylthioalkoxyalkyl, and heteroarylthioalkyl, and
- heterocycle moieties of heterocyclealkoxyalkyl, heterocyclealkoxycarbonyl, heterocyclealkyl, heterocyclealkylcarbonyl, heterocyclecarbonyl, heterocycleoxyalkyl, heterocycleoxycarbonyl, heterocyclethioalkoxyalkyl, and heterocyclethioalkyl,
- at each occurrence, is independently unsubstituted or substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of alkenyl, alkoxy, alkoxyalkyl, alkoxycarbonyl, alkoxycarbonylalkyl, alkyl, alkylcarbonyl, alkylcarbonylalkyl, alkylcarbonyloxy, alkynyl, benzyloxy, carboxy, carboxyalkyl, cyano, cyanoalkyl, ethylenedioxy, formyl, halogen, haloalkyl, hydroxy, hydroxyalkyl, methylenedioxy, mercapto, nitro, phenoxy, thioalkoxy, thioalkoxyalkyl, —NRARB, (NRARB)alkoxy, and (NRARB)alkyl, wherein RA and RB are independently selected from the group consisting of hydrogen and lower alkyl.
22 more elements
Dependencies are inferred from the claim text.