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US 2014/0194457 A1Published application
Carboxamide bioisosteres of opiates
AssigneeRensselaer Polytechnic Institute
InventorMark P. WENTLAND
Life of this patent
Estimating the term…
Abstract
A compound of formula I is disclosed. Compounds of formula I are useful as analgesics, anti-inflammatory agents, anti-diarrheal agents, anticonvulsants, antitussives and anti-addiction medications.
Claims20
A compound of formula I:
- wherein
- R1 and R2 are each independently selected from hydrogen, halogen, —OH, —CN, —CHO, —OCH3, —OCH2CH3, —OCH(CH3)2, —NO2, —COR10, —COOR10, —SO2R10, —CONR10R11, CSNR10R11, —CONR10NR11R12, —CONR10OR11, —CONR10((C(R12)(R13)tCONR10R11, —CONR10((C(R12)(R13)tCOOR11, —C(═S)R10, —C(═NOR11)R10, C(═NR10)R11, —SO2NR10R11, heterocyclyl, optionally substituted lower alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, and (C1-C6)alkylthio;
- or, R1 and R2 together with the atoms to which they are attached, and a fragment selected from —OCH2O—, or —OCH2CH2O—, form a ring,
- wherein when Cy is an aromatic group R1 and R2 cannot both be hydrogen;
- wherein when Cy is an aromatic group R1 and R2 cannot both be halogen;
- R3 is chosen from hydrogen, C1-C8 hydrocarbon, heterocyclyl, aryl and hydroxyalkyl;
- R4 is chosen from hydrogen, hydroxyl, amino, lower alkoxy, C1-C20 alkyl and C1-C20 alkyl substituted with hydroxyl or carbonyl;
- R5 is lower alkyl;
- R6 is lower alkyl;
- R7 is chosen from hydrogen, NR10R11 and —OR10;
- or
- together R4, R5, R6 and R7 may form from one, two, three, or four rings, said rings having optional additional substitution;
- R8 and R8a are both hydrogen or taken together R8 and R8a are ═O;
- R9 is chosen from hydrogen and lower alkyl;
- R10, R11, R12 and R13 are each independently hydrogen, optionally substituted lower alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, hydroxyl, —NR100R101 or optionally substituted lower alkoxy, or
- R10 and R11, together with the nitrogen atom to which they are attached, form an optionally substituted fused carbocyclic or heterocyclic ring having from 5 to 7 ring members of which up to 3 can be heteroatoms selected from N, O and S;
- t is 0, 1, 2, 3, 4, 5, or 6;
- R100 and R101 are each independently hydrogen, optionally substituted lower alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, hydroxyl, or optionally substituted lower alkoxy, or
- R100 and R101, together with the nitrogen atom to which they are attached, form an optionally substituted fused carbocyclic or heterocyclic ring having from 5 to 7 ring members of which up to 3 can be heteroatoms selected from N, O and S;
- Y is a direct bond or —(C(R10)(R11))q-, wherein q is 0, 1, 2, 3, 4 or 5;
- L is a direct bond or —(C(R10)(R11))q-;
- and
- Cy is Ar1—B—Ar2, wherein
- Ar1 is absent, or an aryl or heteroaryl radical having from 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by halogen, lower alkyl, alkenyl, alkynyl, cycloalkyl, —OR10, —NR10R11, CN, —COR10or —COOR10;
- B is a direct bond, —O—, —NR10, —SO2, or —(C(R10)(R11)s-, wherein s is 0, 1, 2, 3, 4 or 5;
- and
- Ar2 is aryl or heteroaryl radical having from 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by halogen, lower alkyl, alkenyl, alkynyl, cycloalkyl, —OR10, —NR10R11, —CN, —COR10or —COOR10,
- wherein when Cy is phenyl or biphenyl, R1 is other than —OCH3.
25 more elements
A compound of formula Ia:
- wherein
- R1 and R2 are each independently selected from hydrogen, halogen, —OH, —CN, —CHO, —OCH3, —OCH2CH3, —OCH(CH3)2, heterocyclyl, optionally substituted lower alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, halo(C1-C6)alkyl, halo(C1-C6)alkoxy, (C1-C6)alkylthio, —NO2, —COR10, —SO2R10, —CONR10R11, —C(═S)R10, —C(═NOR11)R10, C(═NR10R11 and —SO2NR10R11;
- or, R1 and R2 together with the atoms to which they are attached, and a fragment selected from —OCH2O—, or —OCH2CH2O—, form a ring,
- with the proviso that R1 and R2 cannot both be hydrogen;
- R3 is chosen from hydrogen, C1-C8 hydrocarbon, heterocyclyl, aryl and hydroxyalkyl;
- R4 is chosen from hydrogen, hydroxyl, amino, lower alkoxy, C1-C20 alkyl and C1-C20 alkyl substituted with hydroxyl or carbonyl;
- R5 is lower alkyl;
- R6 is lower alkyl;
- R7 is chosen from hydrogen, NR10R11 and —OR10;
- or
- together R4, R5, R6 and R7 may form from one to four rings, said rings having optional additional substitution;
- R8 and R8a are both hydrogen or taken together R8 and R8a are ═O;
- R9 is chosen from hydrogen and lower alkyl;
- R10 and R11 are each independently hydrogen, optionally substituted lower alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, hydroxyl, —NR100R101 or optionally substituted lower alkoxy, or
- R10 and R11, together with the nitrogen atom to which they are attached, form an optionally substituted fused carbocyclic or heterocyclic ring having from 5 to 7 ring members of which up to 3 can be heteroatoms selected from N, O and S;
- R100 and R101 are each independently hydrogen, optionally substituted lower alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted aryl, hydroxyl, or optionally substituted lower alkoxy, or
- R100 and R101, together with the nitrogen atom to which they are attached, form an optionally substituted fused carbocyclic or heterocyclic ring having from 5 to 7 ring members of which up to 3 can be heteroatoms selected from N, O and S;
- Y is a direct bond or —(C(R10)(R11)) q-, wherein q is 0, 1, 2, 3, 4 or 5;
- and
- Cy is Ar1—B—Ar2, wherein
- Ar1 is absent, or an aryl or heteroaryl radical having from 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by halogen, lower alkyl, alkenyl, alkynyl, cycloalkyl, —OR10, —NR10R11, —CN, —COR10or —COOR10;
- B is a direct bond, —O—, —NR10, —SO2, or —(C(R10)(R11)s-, wherein s is 0, 1, 2, 3, 4 or 5;
- and
- Ar2 is aryl or heteroaryl radical having from 1 to 4 N, O and/or S atoms, which may be unsubstituted or mono-, di- or trisubstituted by halogen, lower alkyl, alkenyl, alkynyl, cycloalkyl, —OR10, —NR10R11, —CN, —COR10or —COOR10,
- wherein when Cy is phenyl or biphenyl, R1 is other than —OCH3.
22 more elements
Dependencies are inferred from the claim text.