US 6,673,811 B1Granted

1H-pyrrolo [3,2-b] pyridine-3-carboxylic acid amines as GABAA receptor ligands

AssigneesNeurogen Corporation, Pfizer Inc.

InventorsGeorge D. Maynard, Manuka Ghosh, Christopher J. O'Donnell

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Abstract

Disclosed are 1H-Pyrrolo[3,2-b]pyridine-3-carboxylic acid amides that bind to the benzodiazepine site of GABAA receptors. Such compounds can be used to modulate ligand binding to GABAA receptors in vivo and in vitro, and are particularly useful in the treatment of a variety of central nervous system (CNS) disorders in humans, domesticated companion animals, and livestock animals.

Claims58

Dependent claims

A compound of the Formula:

or a pharmaceutically acceptable salt thereof, wherein R1, R2, and R3 are independently
A) hydrogen, halogen, halo(C1-C6)alkyl, hydroxy, cyano, amino, alkyl, alkoxy, mono- or di-(C1-C6)alkylamino, mono- or di-(C1-C6)alkylamino(C1-C6)alkyl, —C(═O)NR10R11, —C(═O)OR10, and —OC(═O)R10, —C(═O)R10, wherein R10 and R11 are independently hydrogen, C1-C6 alkyl, phenyl, phenyl(C1-C6)alkyl, pyridyl, or pyridyl(C1-C6)alkyl;
B) haloalkoxy, alkenyl, alkynyl, hydroxyalkyl, —D—R20, —E—R35, —C1-C4alkyl-D—R20, —C1-C4alkyl-O—R20, —E—R20—G—R30, —E—L, —E—R20—L, J, —C(═O)—L, or —C1-C4alkyl-J;
where D is —S(O)n—, —S(O)nNH—, —S(O)nNH2, —S(O)nNR30—, —NHC(═O)—, —NHC(═O)H, —NR30C(═O)—, —NR30C(═O)H, —NHS(O)n—, and —NR30S(O)n—;
E and G are independently —NH—, —N(C1-C6alkyl)—, S, and O;
each R20 and R30 is independently a (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C6)alkyl group, where each alkyl and cycloalkyl group contains zero or one or more double or triple bonds and where each carbon atom in the R20 and R30 groups is optionally substituted with one or more substituents independently selected from group C) where C) consists of of oxo, hydroxy, halogen, cyano, amino, C1-C6alkoxy, —NH(C1-C6alkyl), —N(C1-C6alkyl)(C1-C6alkyl), —NHC(═O)(C1-C6alkyl), —N(C1-C6alkyl)C(═O)(C1-C6alkyl), —NHS(O)n(C1-C6alkyl), —S(O)n(C1-C6alkyl), —S(O)nNH(C1-C6alkyl), —S(O)nN(C1-C6alkyl)(C1-C6alkyl), or L, where n is 0, 1, or 2;
each R35 is independently a (C1-C8)straight, (C1-C8)branched, (C3-C8)cyclic alkyl or (C3-C8)cycloalkyl(C1-C6)alkyl group, where each alkyl and cycloalkyl group contains zero or one or more double or triple bonds and where each carbon atom in R35 is independently substituted with one or substituents selected from group C);
J and L are independently selected at each occurrence from saturated, partially unsaturated, and aromatic rings having from 4 to 7 ring atoms, where 0, 1, or 2 of the ring atoms are oxygen or nitrogen and the remaining ring atoms are carbon, where the rings are unsubstituted or substituted with one or more substituents independently selected from
i) halogen, oxo, hydroxy, amino, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxy(C1-C6alkyl), C1-C6haloalkyl, C1-C6haloalkoxy, and mono- or di-(C1-C6)alkylamino;
and
ii) phenyl, pyridyl, pyrimidyl, and pyrazinyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, amino, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, C1-C2haloalkoxy, and mono- or di-(C1-C4)alkylamino;
with the proviso that J is not phenyl or pyridyl;
wherein at least 1 of R1, R2, and R3 is selected from B) R4 is hydrogen, halogen, or hydroxyl;
Ar represents an aryl, arylalkyl, heteroarylalkyl or heteroaryl group, each aryl having 1 or 2 aromatic rings, 4 to 7 ring atoms in each aromatic ring and where 0, 1, or 2 of the ring atoms are oxygen, nitrogen, or sulfur and the remaining ring atoms are carbon and where each ring is optionally substituted by 1 or more of R40;
where each R40 is independently hydroxy, halogen, cyano, nitro, amino, XR50, C1-C4alkyl-XR50, or Y;
X is independently selected at each occurrence from the group consisting of a bond, —CH2—, —CHR60—, —O—, —C(═O)—, —C(═O)O—, —OC(═O)—, —S(O)n—, —NH—, —NR60—, —C(═O)NH—, —C(═O)NR60—, —S(O)nNH—, —S(O)nNR60—, —NHC(═O)—, —NR60C(═O)—, —NHS(O)n—, and —NR60S(O)n—;
R50 and R60 are independently selected at each occurrence from hydrogen, C1-C8 alkyl, C3-C8cycloalkyl, and (C3-C8)cycloalkyl(C1-C6)alkyl, where each alkyl and cycloalkyl contains zero or one or more double or triple bonds, and where each carbon atom of the alkyl, cycloalkyl or cycloalkylalkyl is optionally independently substituted with one or more of oxo, hydroxy, halogen, cyano, amino, C1-C6alkoxy, —NH(C1-C6alkyl), —N(C1-C6alkyl)(C1-C6alkyl), —NHC(═O)(C1-C6alkyl), —N(C1-C6alkyl)C(═O)(C1-C6alkyl), —NHS(O)n(C1-C6alkyl), —S(O)n(C1-C6alkyl), —S(O)nNH(C1-C6alkyl), —S(O)nN(C1-C6alkyl)(C1-C6alkyl), and Z, where n is 0, 1, or 2;
and
Y and Z are independently selected at each occurrence from:
saturated, partially unsaturated, or aromatic rings having from 4 to 7 ring atoms, 0, 1, or 2 ring atoms chosen from oxygen and nitrogen, with remaining ring atoms being carbon, wherein Y and Z are unsubstituted or substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxy(C1-C6alkyl ), C1-C6haloalkyl, C1-C6haloalkoxy, and mono- or di-(C1-C6)alkylamino;
and
each n is independently 0, 1, or 2.

19 more elements

A compound of the Formula:

or a pharmaceutically acceptable salt thereof, wherein R1, R2, and R3 are independently chosen from:
A) hydrogen, halogen, halo(C1-C6)alkyl, hydroxy, cyano, amino, alkyl, alkoxy, mono- or di-(C1-C6)alkylamino, mono- or di-(C1-C6)alkylamino(C1-C6)alkyl, —C(═O)NR10R11, —C(═O)OR10, and —OC(═O)R10, —C(═O)R10, wherein R10 and R11 are independently chosen from hydrogen, C1-C6 alkyl, phenyl, phenyl(C1-C6)alkyl, pyridyl, and pyridyl(C1-C6)alkyl;
B) haloalkoxy, alkenyl, alkynyl, hydroxyalkyl, —D—R20, —E—R35, —C1-C4alkyl-DpR20, —C1-C4alkyl-O—R20, —E—R20—G—R30, —E—L, —E—R20—L, J, —C(═O)—L, and —C1-C4alkyl-J;
wherein D is —S(O)n—, —S(O)nNH—, —S(O)nNH2, —S(O)nNR30—, —NHC(═O)—, —NHC(═O)H, —NR30C(═O)—, —NR30C(═O)H, —NHS(O)n—, and —NR30S(O)n—;
E and G are independently NH, N—C1-C6alkyl, S, and O;
R20, R30, and R35 are independently selected at each occurrence from straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, said straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups consisting of 1 to 8 carbon atoms, and containing zero or one or more double or triple bonds, wherein in R20 and R35 each of the 1 to 8 carbon atoms may be further substituted with one or more substituent(s) independently selected from group C) and in R35 at least one of the 1 to 8 carbon atoms is further substituted by one or more substituent(s) independently selected from group C) wherein group C) consists of:
oxo, hydroxy, halogen, cyano, amino, C1-C6alkoxy, —NH(C1-C6alkyl), —N(C1-C6alkyl)(C1-C6alkyl), —NHC(═O)(C1-C6alkyl), —N(C1-C6alkyl)C(═O)(C1-C6alkyl), —NHS(O)(C1-C6alkyl ), —S(O)n(C1-C6alkyl), —S(O)nNH(C1-C6alkyl), —S(O)nN(C1-C6alkyl)(C1-C6alkyl), and L;
J and L are independently selected at each occurrence from:
saturated, partially unsaturated, or aromatic rings having from 4 to 7 ring atoms, 0, 1, or 2 ring atoms chosen from oxygen and nitrogen, with remaining ring atoms being carbon, which rings are unsubstituted or substituted with one or more substituents independently selected from:
i) halogen, oxo, hydroxy, amino, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxy(C1-C6alkyl), C1-C6haloalkyl, C1-C6haloalkoxy, and mono- or di-(C1-C6)alkylamino and ii)phenyl, pyridyl, pyrimidyl, and pyrazinyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, amino, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, C1-C2haloalkoxy, and mono- or di-(C1-C4)alkylamino;
R4 is hydrogen, halogen, or hydroxyl;
Ar represents heteroaryl or heteroaryl(C1-C6)alkyl, where the heteroaryl is selected from quinolinyl, benzothienyl, indolyl, pryidazinyl, pyazinyl, isoindolyl, isoquinolyl, quinazolinyl, quinoxalinyl, phthalazinyl, imidazolyl, isoxazolyl, pyrazolyl, oxazolyl, thienyl, thiazolyl, indolizinyl, indazolyl, benzothiazolyl, benzimidazolyl, benzofuranyl, benzoisoxolyl, dihydro-benzodioxinyl, furanyl, pyrrolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, oxazolopyridinyl, imidazopyridinyl, isothiazolyl, naphthyridinyl, cinnolinyl, carbazolyl, beta-carbolinyl, isochromanyl, chromanonyl, chromanyl, tetrahydroisoquinolinyl, isoindolinyl, isobenzotetrahydrofuranyl, isobenzotetrahydrothienyl, isobenzothienyl, benzoxazolyl, pyridopyridinyl, benzotetrahydrofuranyl, benzotetrahydrothienyl, purinyl, benzodioxolyl, triazinyl, phenoxazinyl, phenothiazinyl, pteridinyl, benzothiazolyl, imidazopyridinyl, imidazothiazolyl, dihydrobenzisoxazinyl, benzisoxazinyl, benzoxazinyl, dihydrobenzisothiazinyl, benzopyranyl, benzothiopyranyl, coumarinyl, isocoumarinyl, chromanyl, tetrahydroquinolinyl, dihydroquinolinyl, dihydroquinolinonyl, dihydroisoquinolinonyl, dihydrocoumarinyl, dihydroisocoumarinyl, isoindolinonyl, benzodioxanyl, benzoxazolinonyl, pyrrolyl N-oxide, pyrimidinyl N-oxide, pyridazinyl N-oxide, pyrazinyl N-oxide, quinolinyl N-oxide, indolyl N-oxide, indolinyl N-oxide, isoquinolyl N-oxide, quinazolinyl N-oxide, quinoxalinyl N-oxide, phthalazinyl N-oxide, imidazolyl N-oxide, isoxazolyl N-oxide, oxazolyl N-oxide, thiazolyl N-oxide, indolizinyl N-oxide, indazolyl N-oxide, benzothiazolyl N-oxide, benzimidazolyl N-oxide, pyrrolyl N-oxide, oxadiazolyl N-oxide, thiadiazolyl N-oxide, triazolyl N-oxide, tetrazolyl N-oxide, benzothiopyranyl S-oxide, and benzothiopyranyl S,S-dioxide, wherein Ar is optionally substituted by 1 or more of R40;
R40 is independently selected at each occurrence from hydroxy, halogen, cyano, nitro, amino, XR50, C1-C4alkyl-XR50, and Y;
X is independently selected at each occurrence from the group consisting of a bond, —CH2—, —CHR60—, —O—, —C(═O)—, —C(═O)O—, —OC(═O)—, —S(O)n—, —NH—, —NR60—, —C(═O)NH—, —C(═O)NR60—, —S(O)nNH—, —S(O)nNR60—, —NHC(═O)—, —NR60C(═O)—, —NHS(O)n—, and —NR60S(O)n—;
R50 and R60 are independently selected at each occurrence from hydrogen, and straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, said straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups consisting of 1 to 8 carbon atoms, and containing zero or one or more double or triple bonds, each of which may be further substituted with one or more substituent(s) independently selected from oxo, hydroxy, halogen, cyano, amino, C1-C6alkoxy, —NH(C1-C6alkyl), —N(C1-C6alkyl)(C1-C6alkyl), —NHC (═O)(C1-C6alkyl), —N(C1-C6alkyl)C(═O)(C1-C6alkyl), —NHS(O)n(C1-C6alkyl), —S(O)n(C1-C6alkyl), —S(O)nNH(C1-C6alkyl), —S(O)nN(C1-C6alkyl)(C1-C6alkyl), and Z;
Y and Z are independently selected at each occurrence from:
saturated, partially unsaturated, or aromatic rings having from 4 to 7 ring atoms, 0, 1, or 2 ring atoms chosen from oxygen and nitrogen, with remaining ring atoms being carbon, wherein Y and Z are unsubstituted or substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxy(C1-C6alkyl), —C1-C6haloalkyl, C1-C6haloalkoxy, and mono- or di-(C1-C6)alkylamino;
and
n is independently selected at each occurrence from 0, 1, and 2.

16 more elements

A compound of the Formula:

or a pharmaceutically acceptable salt thereof, wherein R1, R2, and R3 are independently chosen from:
A) hydrogen, halogen, halo(C1-C6)alkyl, hydroxy, cyano, amino, alkyl, alkoxy, mono- or di-(C1-C6)alkylamino, mono- or di-(C1-C6)alkylamino(C1-C6)alkyl, —C(═O)NR10R11, —C(═O)OR10, and —OC(═O)R10, —C(═O)R10, wherein R10 and R11 are independently chosen from hydrogen, C1-C6 alkyl, phenyl, phenyl(C1-C6)alkyl, pyridyl, and pyridyl(C1-C6)alkyl;
B) haloalkoxy, alkenyl, alkynyl, hydroxyalkyl, —D—R20, —E—R35, —C1-C4alkyl-D—R20, —C1-C4alkyl-O—R20, —E—R20—G—R30, —E—L, —E—R20—L, J, —C(═O)—L, and —C1-C4alkyl-J;
wherein D is —S(O)n—, —S(O)nNH—, —S(O)nNH2, —S(O)nNR30—, —NHC(═O)—, —NHC(═O)H, —NR30C(═O)—, —NR30C(═O)H, —NHS(O)n—, and —NR30S(O)n—;
E and G are independently NH, N—C1-C6alkyl, S, and O;
R20, R30, and R35 are independently selected at each occurrence from straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, said straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups consisting of 1 to 8 carbon atoms, and containing zero or one or more double or triple bonds, wherein in R20 and R35 each of the 1 to 8 carbon atoms may be further substituted with one or more substituent(s) independently selected from group C) and in R35 at least one of the 1 to 8 carbon atoms is further substituted by one or more substituent(s) independently selected from group C) wherein group C) consists of:
oxo, hydroxy, halogen, cyano, amino, C1-C6alkoxy, —NH(C1-C6alkyl), —N(C1-C6alkyl)(C1-C6alkyl), —NHC(═O)(C1-C6alkyl), —N(C1-C6alkyl)C(═O)(C1-C6alkyl), —NHS(O)n(C1-C6alkyl), —S(O)n(C1-C6alkyl), —S(O)nNH(C1-C6alkyl), —S(O)nN(C1-C6alkyl)(C1-C6alkyl), and L;
J and L are independently selected at each occurrence from:
saturated, partially unsaturated, or aromatic rings having from 4 to 7 ring atoms, 0, 1, or 2 ring atoms chosen from oxygen and nitrogen, with remaining ring atoms being carbon, which rings are unsubstituted or substituted with one or more substituents independently selected from i) halogen, oxo, hydroxy, amino, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxy(C1-C6alkyl), C1-C6haloalkyl, C1-C6haloalkoxy, and mono- or di-(C1-C6)alkylamino and ii)phenyl, pyridyl, pyrimidyl, and pyrazinyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, amino, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, C1-C2haloalkoxy, and mono- or di-(C1-C4)alkylamino;
R4 is hydrogen, halogen, or hydroxyl;
Ar represents phenyl, pyridyl, or pyrimidinyl wherein
Ar is optionally substituted by 1 or more of R40;
R40 is independently selected at each occurrence from hydroxy, halogen, cyano, nitro, amino, C1-C6alkyl, C1-C6alkoxy, C1-C6alkanoyl, C3-C7cycloalkyl, C3-C7cycloalkyl(C1-C4)alkyl, C3-C7cycloalkyl-O—, C3-C7cycloalkyl(C1-C4)alkoxy-, C2-C6alkenyl, C1-C6alkylthio-, halo(C1-C6)alkyl, and halo(C1-C6)alkoxy, and
Ar is substituted by at least one of —E—R50—G—R60, —E—R50—G—Y, C1-C4alkyl-XR50, —NH—R60—Y, —(NR50)R60—Y, and Y;
X is independently selected at each occurrence from the group consisting of —O—, —C(═O)—, —C(═O)O—, —OC(═O)—, —S(O)n—, —NH—, —NR60—, —C(═O)NH—, —C(═O)NR60—, —S(O)nNH—, —S(O)nNR60—, —NHC(═O)—, —NR60C(═O)—, —NHS(O)n—, and —NR60S(O)n—;
R50 and R60 are independently selected at each occurrence from:
hydrogen, and straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups, said straight, branched, and cyclic alkyl groups, and (cycloalkyl)alkyl groups consisting of 1 to 8 carbon atoms, and containing zero or one or more double or triple bonds, which 1 to 8 carbon atoms may be further substituted with one or more substituent(s) independently selected from oxo, hydroxy, halogen, cyano, amino, C1-C6alkoxy, —NH(C1-C6alkyl), —N(C1-C6alkyl)(C1-C6alkyl), —NHC(═O)(C1-C6alkyl), —N(C1-C6alkyl)C(═O)(C1-C6alkyl), —NHS(O)n(C1-C6alkyl), —S(O)n(C1-C6alkyl), —S(O)nNH(C1-C6alkyl), —S(O)nN(C1-C6alkyl)(C1-C6alkyl), and Z;
Y and Z are independently selected at each occurrence from:
saturated, partially unsaturated, or aromatic rings having from 4 to 7 ring atoms, 0, 1, or 2 ring atoms chosen from oxygen and nitrogen, with remaining ring atoms being carbon, wherein Y and Z are unsubstituted or substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxy(C1-C6alkyl), C1-C6haloalkyl, C1-C6haloalkoxy, and mono- or di-(C1-C6)alkylamino;
and
n is independently selected at each occurrence from 0, 1, and 2.

18 more elements

A compound of the formula

or a pharmaceutically acceptable salt thereof, wherein
R1 is amino(C1-C6)alkoxy, mono(C1-C3)alkylamino(C1-C6)alkoxy, di (C1-C3)alkylamino(C1-C6)alkoxy, pyridyl(C1-C6)alkoxy, hydroxy(C1-C6)alkoxy, (C1-C4)alkoxy(C1-C6)alkoxy, piperazinyl(C1-C6)alkoxy wherein the piperazinyl group is optionally substituted with (C1-C6)alkyl, morpholinyl(C1-C6)alkoxy, or thiomorpholinyl(C1-C6)alkoxy;
R2 and R3 are independently selected from H, (C1-C6)alkyl, halogen or (C1-C6)alkoxy;
Ar is pyridyl, isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, pyrazolyl, pyrimidyl, or pyridazinyl, each of which is unsubstituted or substituted with 1, 2, or 3 groups that are independently (C1-C6)alkyl, (C1-C6)alkoxy, halogen, OCF3, or CF3.

1 more element

Dependencies are inferred from the claim text.

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Abstract

A compound of the Formula:

or a pharmaceutically acceptable salt thereof, wherein R1, R2, and R3 are independently
A) hydrogen, halogen, halo(C1-C6)alkyl, hydroxy, cyano, amino, alkyl, alkoxy, mono- or di-(C1-C6)alkylamino, mono- or di-(C1-C6)alkylamino(C1-C6)alkyl, —C(═O)NR10R11, —C(═O)OR10, and —OC(═O)R10, —C(═O)R10, wherein R10 and R11 are independently hydrogen, C1-C6 alkyl, phenyl, phenyl(C1-C6)alkyl, pyridyl, or pyridyl(C1-C6)alkyl;
B) haloalkoxy, alkenyl, alkynyl, hydroxyalkyl, —D—R20, —E—R35, —C1-C4alkyl-D—R20, —C1-C4alkyl-O—R20, —E—R20—G—R30, —E—L, —E—R20—L, J, —C(═O)—L, or —C1-C4alkyl-J;
where D is —S(O)n—, —S(O)nNH—, —S(O)nNH2, —S(O)nNR30—, —NHC(═O)—, —NHC(═O)H, —NR30C(═O)—, —NR30C(═O)H, —NHS(O)n—, and —NR30S(O)n—;
E and G are independently —NH—, —N(C1-C6alkyl)—, S, and O;
each R20 and R30 is independently a (C1-C8)alkyl, (C3-C8)cycloalkyl or (C3-C8)cycloalkyl(C1-C6)alkyl group, where each alkyl and cycloalkyl group contains zero or one or more double or triple bonds and where each carbon atom in the R20 and R30 groups is optionally substituted with one or more substituents independently selected from group C) where C) consists of of oxo, hydroxy, halogen, cyano, amino, C1-C6alkoxy, —NH(C1-C6alkyl), —N(C1-C6alkyl)(C1-C6alkyl), —NHC(═O)(C1-C6alkyl), —N(C1-C6alkyl)C(═O)(C1-C6alkyl), —NHS(O)n(C1-C6alkyl), —S(O)n(C1-C6alkyl), —S(O)nNH(C1-C6alkyl), —S(O)nN(C1-C6alkyl)(C1-C6alkyl), or L, where n is 0, 1, or 2;
each R35 is independently a (C1-C8)straight, (C1-C8)branched, (C3-C8)cyclic alkyl or (C3-C8)cycloalkyl(C1-C6)alkyl group, where each alkyl and cycloalkyl group contains zero or one or more double or triple bonds and where each carbon atom in R35 is independently substituted with one or substituents selected from group C);
J and L are independently selected at each occurrence from saturated, partially unsaturated, and aromatic rings having from 4 to 7 ring atoms, where 0, 1, or 2 of the ring atoms are oxygen or nitrogen and the remaining ring atoms are carbon, where the rings are unsubstituted or substituted with one or more substituents independently selected from
i) halogen, oxo, hydroxy, amino, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxy(C1-C6alkyl), C1-C6haloalkyl, C1-C6haloalkoxy, and mono- or di-(C1-C6)alkylamino;
and
ii) phenyl, pyridyl, pyrimidyl, and pyrazinyl, each of which is unsubstituted or substituted with from 1 to 3 substituents independently chosen from halogen, hydroxy, amino, cyano, C1-C4alkyl, C1-C4alkoxy, C1-C2haloalkyl, C1-C2haloalkoxy, and mono- or di-(C1-C4)alkylamino;
with the proviso that J is not phenyl or pyridyl;
wherein at least 1 of R1, R2, and R3 is selected from B) R4 is hydrogen, halogen, or hydroxyl;
Ar represents an aryl, arylalkyl, heteroarylalkyl or heteroaryl group, each aryl having 1 or 2 aromatic rings, 4 to 7 ring atoms in each aromatic ring and where 0, 1, or 2 of the ring atoms are oxygen, nitrogen, or sulfur and the remaining ring atoms are carbon and where each ring is optionally substituted by 1 or more of R40;
where each R40 is independently hydroxy, halogen, cyano, nitro, amino, XR50, C1-C4alkyl-XR50, or Y;
X is independently selected at each occurrence from the group consisting of a bond, —CH2—, —CHR60—, —O—, —C(═O)—, —C(═O)O—, —OC(═O)—, —S(O)n—, —NH—, —NR60—, —C(═O)NH—, —C(═O)NR60—, —S(O)nNH—, —S(O)nNR60—, —NHC(═O)—, —NR60C(═O)—, —NHS(O)n—, and —NR60S(O)n—;
R50 and R60 are independently selected at each occurrence from hydrogen, C1-C8 alkyl, C3-C8cycloalkyl, and (C3-C8)cycloalkyl(C1-C6)alkyl, where each alkyl and cycloalkyl contains zero or one or more double or triple bonds, and where each carbon atom of the alkyl, cycloalkyl or cycloalkylalkyl is optionally independently substituted with one or more of oxo, hydroxy, halogen, cyano, amino, C1-C6alkoxy, —NH(C1-C6alkyl), —N(C1-C6alkyl)(C1-C6alkyl), —NHC(═O)(C1-C6alkyl), —N(C1-C6alkyl)C(═O)(C1-C6alkyl), —NHS(O)n(C1-C6alkyl), —S(O)n(C1-C6alkyl), —S(O)nNH(C1-C6alkyl), —S(O)nN(C1-C6alkyl)(C1-C6alkyl), and Z, where n is 0, 1, or 2;
and
Y and Z are independently selected at each occurrence from:
saturated, partially unsaturated, or aromatic rings having from 4 to 7 ring atoms, 0, 1, or 2 ring atoms chosen from oxygen and nitrogen, with remaining ring atoms being carbon, wherein Y and Z are unsubstituted or substituted with one or more substituents independently selected from halogen, oxo, hydroxy, amino, cyano, C1-C6alkyl, C1-C6alkoxy, C1-C6alkoxy(C1-C6alkyl ), C1-C6haloalkyl, C1-C6haloalkoxy, and mono- or di-(C1-C6)alkylamino;
and
each n is independently 0, 1, or 2.

19 more elements