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US 2004/0063756 A1Published application
2-Aminoquinolines as melanin concentrating hormone receptor antagonists
AssigneeAbbott Laboratories
InventorsChristine A. Collins, Ju Gao, Philip R. Kym, Jared C. Lewis, Andrew J. Souers, Anil Vasudevan, Dariusz Wodka
Life of this patent
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Abstract
The present invention is related to compounds of formula (I), 1 or a therapeutically suitable salt or prodrug thereof, which antagonize the effects of melanin-concentrating hormone (MCH) through the melanin concentrating hormone receptor and are useful for the prevention or treatment of eating disorders, weight gain and obesity.
Claims16
A compound according to formula (I),
- 25
- or a therapeutically suitable salt or prodrug thereof, wherein
- L1 is a bond or is a member selected from the group consisting of —C(O)—, —O—, —S—, —S(O)—, and —S(O)2—;
- R1 is a member selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, arylalkyl, arylalkoxy, arylcarbonyl, heterocycle, heterocyclealkyl, RARBN—, and RARBNcarbonyl;
- R2 is a member selected from the group consisting of alkyl, alkoxy, alkenyl, alkoxyalkyl, aryl, arylalkyl, aryloxyalkyl, cycloalkyl, cycloalkylalkyl, haloalkyl, heterocycle, heterocyclealkyl, heterocycleoxyalkyl, heterocycleoxyalkoxyalkyl, R7L2R6—, RASalkyl, and RARBNalkyl;
- R3 is a member selected from the group consisting of hydrogen, alkyl, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- R4, and R5 are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxy, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- R6 and R7 are each independently a member selected from the group consisting of aryl, cycloalkyl, and heterocycle;
- RA and RB are each independently a member selected from the group consisting of hydrogen, alkyl, aryl and heterocycle;
- L2 is —(CH2)mX(CH2)n—,
- X is a member selected from the group consisting of —C(O)—, —O—, —S—, —S(O)—, —S(O)2— or is a covalent bond,
- m is 0, 1, 2, 3, or 4;
- n is 0, 1, 2, 3, or 4;
- and
- provided that
- if i) any of R3, R4, or R5 is alkyl or alkoxy, or
- if ii) L is a bond and R2 is either alkyl or alkoxy;
- then
- R1 must be other than hydrogen.
16 more elements
A compound according to formula (Ia),
- 26
- or a therapeutically suitable salt or prodrug thereof, wherein
- L1 is —O—;
- R1 is selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, arylalkyl, arylalkoxy, arylcarbonyl, heterocycle, heterocyclealkyl, RARBN—, and RARBNcarbonyl;
- R2 is selected from the group consisting of alkyl, alkenyl-;
- R3 is a member selected from the group consisting of hydrogen, alkyl, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- R4, and R5 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- RA and RB are each independently selected from the group consisting of hydrogen, alkyl, aryl and heterocycle;
- provided that
- if i) any of R3, R4, or R5 is alkyl or alkoxy, or
- if ii) L is a bond and R2 is either alkyl or alkoxy;
- then
- R1 must be other than hydrogen.
10 more elements
A compound according to formula (Ib),
- 27
- or a therapeutically suitable salt or prodrug thereof, wherein
- L1 is —O—;
- R1 is a member selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, arylalkyl, arylalkoxy, arylcarbonyl, heterocycle, heterocyclealkyl, RARBN—, and RARBNcarbonyl;
- R2 is alkyl, wherein alkyl is C6 or larger;
- R3 is a member selected from the group consisting of hydrogen, alkyl, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- R4, and R5 are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxy, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- and
- RA and RB are each independently a member selected from the group consisting of hydrogen, alkyl, aryl and heterocycle.
6 more elements
A compound according to formula (Ic),
- 28
- or a therapeutically suitable salt or prodrug thereof, wherein
- L1 is —O—;
- R1 is a member selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, arylalkyl, arylalkoxy, arylcarbonyl, heterocycle, heterocyclealkyl, RARBN—, and RARBNcarbonyl;
- R2 is a member selected from the group consisting of alkoxyalkyl, haloalkyl, RASalkyl, and RARBNalkyl;
- R3 is a member selected from the group consisting of hydrogen, alkyl, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- R4, and R5 are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxy, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- RA and RB are each independently a member selected from the group consisting of hydrogen, alkyl, aryl and heterocycle.
5 more elements
A compound according to formula (Id),
- 29
- or a therapeutically suitable salt or prodrug thereof, wherein
- L1 is —O—;
- R1 is a member selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, arylalkyl, arylalkoxy, arylcarbonyl, heterocycle, heterocyclealkyl, RARBN—, and RARBNcarbonyl;
- R2 is a member selected from the group consisting of aryl, cycloalkyl and heterocycle;
- R3 is a member selected from the group consisting of hydrogen, alkyl, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- R4, and R5 are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxy, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- RA and RB are each independently a member selected from the group consisting of hydrogen, alkyl, aryl and heterocycle.
5 more elements
A compound according to formula (Ie),
- 30
- or a therapeutically suitable salt or prodrug thereof, wherein
- L1 is —O—;
- R1 is a member selected from the group consisting of hydrogen, alkyl, alkoxy, aryl, arylalkyl, arylalkoxy, arylcarbonyl, heterocycle, heterocyclealkyl, RARBN—, and RARBNcarbonyl;
- R2 is a member selected from the group consisting of arylalkyl, aryloxyalkyl, cycloalkylalkyl, heterocyclealkyl, heterocycleoxyalkyl, heterocycleoxyalkoxyalkyl, R7L2R6—;
- R3 is a member selected from the group consisting of hydrogen, alkyl, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- R4, and R5 are each independently a member selected from the group consisting of hydrogen, alkyl, alkoxy, hydroxy, cyano, halo, haloalkoxy, RARBN—, and alkylcarbonylNH—;
- RA and RB are each independently a member selected from the group consisting of hydrogen, alkyl, aryl and heterocycle.
5 more elements
The following additional compounds
- 8-isopropoxyquinolin-2-amine;
- 8-sec-butoxyquinolin-2-amine;
- 8-(1-methylbutoxy)quinolin-2-amine;
- 8-(1,2-dimethylpropoxy)quinolin-2-amine;
- 8-(1-ethylpropoxy)quinolin-2-amine;
- 8-ethoxyquinolin-2-amine;
- 8-propoxyquinolin-2-amine;
- 8-butoxyquinolin-2-amine;
- 8-isobutoxyquinolin-2-amine;
- 8-(pentyloxy)quinolin-2-amine;
- 8-(2-methylbutoxy)quinolin-2-amine;
- 8-(3-methylbutoxy)quinolin-2-amine;
- 8-(((1R)-1-methylpropyl)oxy)quinolin-2-amine;
- 8-(((1S)-1,2-dimethylpropyl)oxy)quinolin-2-amine;
- 8-(((1R)-1,2-dimethylpropyl)oxy)quinolin-2-amine;
- 8-(((1S)-1-methylpropyl)oxy)quinolin-2-amine;
- 8-((1-isopropylbut-3-enyl)oxy)quinolin-2-amine;
- 8-((1,5-dimethylhex-4-enyl)oxy)quinolin-2-amine;
- 8-((2E)-but-2-enyloxy)quinolin-2-amine;
- 8-hexylquinolin-2-amine;
- 8-(1-methylpentyl)quinolin-2-amine;
- 8-(1-ethylbutyl)quinolin-2-amine;
- 8-(1-ethylpentyl)quinolin-2-amine;
- 3-((2-aminoquinolin-8-yl)oxy)propan-1-ol;
- and
- 4-((2-aminoquinolin-8-yl)oxy)pentan-1-ol.
23 more elements
A method of treating disorders mediated by MCH through the MCH receptor comprising administering a therapeutically effective amount of a compound of formula (I).
A method for treating eating disorders, weight gain and obesity comprising administering a therapeutically effective amount of a compound of formula (I).
A method for treating abnormalities in reproduction and sexual behavior, thyroid hormone secretion, diuresis and water/electrolyte homeostasis, sensory processing, memory, sleeping, arousal, anxiety, depression, seizures, neurodegeneration and psychiatric disorders comprising administering a therapeutically effective amount of a compound of formula (I).
A pharmaceutical composition comprising a therapeutically effective amount of a compound of formula (I) in combination with a pharmaceutically suitable carrier.
Dependencies are inferred from the claim text.