US 6,310,212 B1Granted

4-substituted quinoline derivatives

AssigneeNeurogen Corporation

InventorsJun Yuan, Alan Hutchinson

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Abstract

Disclosed are compounds of the Formula I where R1, R2, R3, R4, X, Y1, and Y2 are defined herein. These compounds bind with high affinity to GABAA receptors. Also disclosed are pharmaceutical compositions comprising these compounds, and methods of treating patients suffering from certain central nervous system and peripheral diseases or disorders with these pharmaceutical compositions. This invention also relates to the use of such compounds in combination with one or more other CNS agents to potentiate the effects of the other CNS agents. The compounds of this invention are also useful as probes for the localization of GABAA receptors.

Claims14

Dependent claims

A compound of the formula:

or a pharmaceutically acceptable salt or pharmaceutically acceptable solvate thereof, wherein:
R1 is selected from
hydrogen, halogen, hydroxy, C1-6 alkyl, —O(C1-6 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-6 alkyl), —SO2N(C1-6 alkyl)(C1-6 alkyl), amino, —NH(C1-6 alkyl), —N(C1-6 alkyl)(C1-6 alkyl), —N(C1-6 alkyl)CO(C1-6 alkyl), —N(C1-6 alkyl)CO2(C1-6 alkyl), —NHSO2(C1-6 alkyl), —N(C1-6 alkyl)SO2(C1-6 alkyl), —SO2NHCO(C1-6 alkyl), —CONHSO2(C1-6 alkyl), —CON(C1-6 alkyl)(C1-6 alkyl), —CO2(C1-6 alkyl), —S(C1-6 alkyl), —SO(C1-6 alkyl), or —SO2(C1-6 alkyl),
wherein said C1-6 alkyl is straight, branched or cyclic, may contain one or two double or triple bonds, and is unsubstituted or substituted with one or more substituents selected from hydroxy, oxo, fluoro, amino, C1-3 alkoxy;
R2 is
(1) C1-8 alkyl, wherein said C1-8 alkyl is straight, branched or cyclic, may contain one or two double or triple bonds, and is unsubstituted or substituted with one or more of the substituents selected from:
(i) hydroxy,
(ii) oxo,
(iii) fluoro,
(iv) amino,
(v) Ar1, wherein Ar1 is independently selected at each occurrence from phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, imidazolyl, benzoimidazolyl, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, isothiazolyl, benzisothiazolyl, triazolyl, tetrazolyl, pyrazolyl, and benzopyrazolyl, each of which is unsubstituted or substituted with one or more substituents selected from:
hydrogen, halogen, hydroxy, C1-6 alkyl, —O(C1-6 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-6 alkyl), —SO2N(C1-6 alkyl)(C1-6 alkyl), amino, —NH(C1-6 alkyl), —N(C1-6 alkyl)(C1-6 alkyl), —N(C1-6 alkyl)CO(C1-6 alkyl), —N(C1-6 alkyl)CO2(C1-6 alkyl), —NHSO2(C1-6 alkyl), —N(C1-6 alkyl)SO2(C1-6 alkyl), —SO2NHCO(C1-6 alkyl), —CONHSO2(C1-6 alkyl), —CON(C1-6 alkyl)(C1-6 alkyl), —CO2(C1-6 alkyl), —S(C1-6 alkyl), —SO(C1-6 alkyl), or —SO2(C1-6 alkyl), wherein C1-6 alkyl, is defined as above,
(vi) —NR5R6, wherein R5 and R6 are independently selected at each occurrence from:
(a) hydrogen,
(b) C1-6 alkyl, wherein C1-6 alkyl is as defined above,
(c) —(CH2)n-Ar1, wherein n is independently selected at each occurrence from 0, 1 or 2,
(d) or the groups R5 and R6 are joined together to form a 4- to 8-membered ring which may contain one or two double bonds, or one or two oxo, or one or two O, S or N—R7 wherein R7 is independently selected at each occurrence from hydrogen, C1-6 alkyl, —(CH2)n-Ar1,
(vii) —OR5, wherein R5 is as defined above,
(viii) —CONR5R6 wherein R5 and R6 are as defined above,
(ix) —CO2 R5, wherein said R5 is as defined above;
(2) Ar2, wherein Ar2 is independently selected at each occurrence from phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, imidazolyl, benzoimidazolyl, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, isothiazolyl, benzisothiazolyl, triazolyl, tetrazolyl, pyrazolyl, or benzopyrazolyl, and is unsubstituted and substituted with one or more substituents selected from:
hydrogen, halogen, hydroxy, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(C1-8 alkyl)(C1-8 alkyl), amino, —NH(C1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-8 alkyl)SO2(C1-8 alkyl), —SO2NHCO (C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), —SO(C1-8 alkyl), or —SO2(C1-8 alkyl), wherein said C1-8 alkyl is as defined above;
(3) —NR8R9, wherein R8 and R9 are independently selected at each occurrence from:
(a) hydrogen,
(b) Ar2,
(c) C1-8 alkyl, wherein said C1-8 alkyl is as defined above;
or the groups R8 and R9 are joined together to form a which ring may contain one or more double bonds;
one or more oxo;
one or more O, S(O)n, N—R7 wherein n and R7 are as defined above;
or one or more of hydroxy, halogen, amino, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(C1-8 alkyl)(C1-8 alkyl), amino, —NH(C1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-8 alkyl)SO2(C1-8 alkyl), —SO2NHCO(C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), —SO(C1-8 alkyl) or —SO2(C1-8 alkyl);
or
(4) —OR8;
R4 is selected from
hydrogen, halogen, hydroxy, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(1-8 alkyl)(C1-8 alkyl), amino, —NH(1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-6 alkyl)SO2(C1-8 alkyl), —SO2NHCO(C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), —SO(C1-8 alkyl), —SO2(C1-8 alkyl), and Ar2;
X is N—R10, wherein R10 is C1-8 alkyl or an electron pair;
Y1 is —CR11R12—, —CR11R12(CH2)p—, or (CH2)pCR11R12—;
where p is 0, 1, or 2;
Y2 is —CR11R12—;
R11 and R12 are independently selected at each occurrence from:
(1) hydrogen, and
(2) C1-8 alkyl;
or
R10 and R11 may be joined to form a 5- to 8-membered ring which may contain one or more double bonds;
one O, S(O)n, or N—R7 wherein n and R7 are as defined above;
and which may be substituted with one or more of hydroxy, halogen, amino, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(C1-8 alkyl)(C1-8 alkyl), amino, —NH(C1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-8 alkyl)SO2(C1-8 alkyl), —SO2NHCO(C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), and —SO(C1-8 alkyl).

42 more elements

A compound of the formula:

or a pharmaceutically acceptable salt or solvate thereof wherein:
R1 is selected from hydrogen, halogen, hydroxy, C1-6 alkyl, —O(C1-6 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-6 alkyl), —SO2N(C1-6 alkyl)(C1-6 alkyl), amino, —NH(C1-6 alkyl), —N(C1-6 alkyl)(C1-6 alkyl), —N(C1-6 alkyl)CO(C1-6 alkyl), —N(C1-6 alkyl)CO2(C1-6 alkyl), —NHSO2(C1-6 alkyl), —N(C1-6 alkyl)SO2(C1-6 alkyl), —SO2NHCO(C1-6 alkyl), —CONHSO2(C1-6 alkyl), —CON(C1-6 alkyl)(C1-6 alkyl), —CO2(C1-6 alkyl), —S(C1-6 alkyl), —SO(C1-6 alkyl), or —SO2(C1-6 alkyl),
wherein said C1-6 alkyl is straight, branched or cyclic, may contain one or two double or triple bonds, and is unsubstituted or substituted with one or more substituents selected from hydroxy, oxo, fluoro, amino, C1-3 alkoxy;
R2 and R3 are independently selected from
(1) C1-8 alkyl, wherein said C1-8 alkyl is straight, branched or cyclic, may contain one or two double or triple bonds, and is unsubstituted or substituted with one or more of the substituents selected from:
(i) hydroxy,
(ii) oxo,
(iii) fluoro,
(iv) amino,
(v) Ar1, wherein Ar1 is independently selected at each occurrence from phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, imidazolyl, benzoimidazolyl, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, isothiazolyl, benzisothiazolyl, triazolyl, tetrazolyl, pyrazolyl, and benzopyrazolyl, each of which is unsubstituted or substituted with one or more substituents selected from:
hydrogen, halogen, hydroxy, C1-6 alkyl, —O(C1-6 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-6 alkyl), —SO2N(C1-6 alkyl)(C1-6 alkyl), amino, —NH(C1-6 alkyl), —N(C1-6 alkyl)(C1-6 alkyl), —N(C1-6 alkyl)CO(C1-6 alkyl), —N(C1-6 alkyl)CO2(C1-6 alkyl), —NHSO2(C1-6 alkyl), —N(C1-6 alkyl)SO2(C1-6 alkyl), —SO2NHCO(C1-6 alkyl), —CONHSO2(C1-6 alkyl), —CON(C1-6 alkyl)(C1-6 alkyl), —CO2(C1-6 alkyl), —S(C1-6 alkyl), —SO(C1-6 alkyl), or —SO2(C1-6 alkyl), wherein C1-6 alkyl, is defined as above,
(vi) —NR5R6, wherein R5 and R6 are independently selected at each occurrence from:
(a) hydrogen,
(b) C1-6 alkyl, wherein C1-6 alkyl is as defined above,
(c) —(CH2)n-Ar1, wherein n is independently selected at each occurrence from 0, 1 or 2,
(d) or the groups R5 and R6 are joined together to form a 4- to 8-membered ring which may contain one or two double bonds, or one or two oxo, or one or two O, S or N—R7 wherein R7 is independently selected at each occurrence from hydrogen, C1-6 alkyl, —(CH2)n-Ar1,
(vii) —OR5, wherein R5 is as defined above,
(viii) —CONR5R6 wherein R5 and R6 are as defined above,
(ix) —CO2R5, wherein said R5 is as defined above;
(2) Ar2, wherein Ar2 is independently selected at each occurrence from phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, imidazolyl, benzoimidazolyl, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, isothiazolyl, benzisothiazolyl, triazolyl, tetrazolyl, pyrazolyl, or benzopyrazolyl, and is unsubstituted and substituted with one or more substituents selected from:
hydrogen, halogen, hydroxy, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(C1-8 alkyl)(C1-8 alkyl), amino, —NH(C1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-8 alkyl)SO2(C1-8 alkyl), —SO2NHCO(C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), —SO(C1-8 alkyl), or —SO2(C1-8 alkyl), wherein said C1-8 alkyl is as defined above;
(3) —NR8R9, wherein R8 and R9 are independently selected at each occurrence from:
(a) hydrogen,
(b) Ar2,
(c) C1-8 alkyl, wherein said C1-8 alkyl is as defined above;
or the groups R8 and R9 are joined together to form a which ring may contain one or more double bonds;
one or more oxo;
one or more O, S(O)n, N—R7 wherein n and R7 are as defined above;
or one or more of hydroxy, halogen, amino, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(C1-8 alkyl)(C1-8 alkyl), amino, —NH(C1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-8 alkyl)SO2(C1-8 alkyl), —SO2NHCO(C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), —SO(C1-8 alkyl), or —SO2(C1-8 alkyl);
and
(4) —OR8;
R4 is
hydrogen, halogen, hydroxy, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(C1-8 alkyl)(C1-8 alkyl), amino, —NH(C1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-6 alkyl)SO2(C1-8 alkyl), —SO2NHCO(C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), —SO(C1-8 alkyl), —SO2(C1-8 alkyl), or Ar2;
Y1 is —CR11R12—, —CR11R12(CH2)p—, or (CH2)pCR11R12 where
p is 0, 1, or 2;
R11 and R12 are independently selected at each occurrence from:
(1) hydrogen;
and
(2) C1-8 alkyl;
and the M ring is a 5- to 8-membered ring which may contain one or more double bonds, one O, S(O)n or N—R7, wherein n and R7 are as defined above, and which ring may be substituted with one or more of hydroxy, halogen, amino, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(C1-8 alkyl)(C1-8 alkyl), amino, —NH(C1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-8 alkyl)SO2(C1-8 alkyl), —SO2NHCO C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), and —SO(C1-8 alkyl).

37 more elements

Dependencies are inferred from the claim text.

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Abstract

A compound of the formula:

or a pharmaceutically acceptable salt or pharmaceutically acceptable solvate thereof, wherein:
R1 is selected from
hydrogen, halogen, hydroxy, C1-6 alkyl, —O(C1-6 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-6 alkyl), —SO2N(C1-6 alkyl)(C1-6 alkyl), amino, —NH(C1-6 alkyl), —N(C1-6 alkyl)(C1-6 alkyl), —N(C1-6 alkyl)CO(C1-6 alkyl), —N(C1-6 alkyl)CO2(C1-6 alkyl), —NHSO2(C1-6 alkyl), —N(C1-6 alkyl)SO2(C1-6 alkyl), —SO2NHCO(C1-6 alkyl), —CONHSO2(C1-6 alkyl), —CON(C1-6 alkyl)(C1-6 alkyl), —CO2(C1-6 alkyl), —S(C1-6 alkyl), —SO(C1-6 alkyl), or —SO2(C1-6 alkyl),
wherein said C1-6 alkyl is straight, branched or cyclic, may contain one or two double or triple bonds, and is unsubstituted or substituted with one or more substituents selected from hydroxy, oxo, fluoro, amino, C1-3 alkoxy;
R2 is
(1) C1-8 alkyl, wherein said C1-8 alkyl is straight, branched or cyclic, may contain one or two double or triple bonds, and is unsubstituted or substituted with one or more of the substituents selected from:
(i) hydroxy,
(ii) oxo,
(iii) fluoro,
(iv) amino,
(v) Ar1, wherein Ar1 is independently selected at each occurrence from phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, imidazolyl, benzoimidazolyl, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, isothiazolyl, benzisothiazolyl, triazolyl, tetrazolyl, pyrazolyl, and benzopyrazolyl, each of which is unsubstituted or substituted with one or more substituents selected from:
hydrogen, halogen, hydroxy, C1-6 alkyl, —O(C1-6 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-6 alkyl), —SO2N(C1-6 alkyl)(C1-6 alkyl), amino, —NH(C1-6 alkyl), —N(C1-6 alkyl)(C1-6 alkyl), —N(C1-6 alkyl)CO(C1-6 alkyl), —N(C1-6 alkyl)CO2(C1-6 alkyl), —NHSO2(C1-6 alkyl), —N(C1-6 alkyl)SO2(C1-6 alkyl), —SO2NHCO(C1-6 alkyl), —CONHSO2(C1-6 alkyl), —CON(C1-6 alkyl)(C1-6 alkyl), —CO2(C1-6 alkyl), —S(C1-6 alkyl), —SO(C1-6 alkyl), or —SO2(C1-6 alkyl), wherein C1-6 alkyl, is defined as above,
(vi) —NR5R6, wherein R5 and R6 are independently selected at each occurrence from:
(a) hydrogen,
(b) C1-6 alkyl, wherein C1-6 alkyl is as defined above,
(c) —(CH2)n-Ar1, wherein n is independently selected at each occurrence from 0, 1 or 2,
(d) or the groups R5 and R6 are joined together to form a 4- to 8-membered ring which may contain one or two double bonds, or one or two oxo, or one or two O, S or N—R7 wherein R7 is independently selected at each occurrence from hydrogen, C1-6 alkyl, —(CH2)n-Ar1,
(vii) —OR5, wherein R5 is as defined above,
(viii) —CONR5R6 wherein R5 and R6 are as defined above,
(ix) —CO2 R5, wherein said R5 is as defined above;
(2) Ar2, wherein Ar2 is independently selected at each occurrence from phenyl, naphthyl, thienyl, benzothienyl, pyridyl, quinolyl, pyrazinyl, pyrimidyl, imidazolyl, benzoimidazolyl, furanyl, benzofuranyl, thiazolyl, benzothiazolyl, isothiazolyl, benzisothiazolyl, triazolyl, tetrazolyl, pyrazolyl, or benzopyrazolyl, and is unsubstituted and substituted with one or more substituents selected from:
hydrogen, halogen, hydroxy, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(C1-8 alkyl)(C1-8 alkyl), amino, —NH(C1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-8 alkyl)SO2(C1-8 alkyl), —SO2NHCO (C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), —SO(C1-8 alkyl), or —SO2(C1-8 alkyl), wherein said C1-8 alkyl is as defined above;
(3) —NR8R9, wherein R8 and R9 are independently selected at each occurrence from:
(a) hydrogen,
(b) Ar2,
(c) C1-8 alkyl, wherein said C1-8 alkyl is as defined above;
or the groups R8 and R9 are joined together to form a which ring may contain one or more double bonds;
one or more oxo;
one or more O, S(O)n, N—R7 wherein n and R7 are as defined above;
or one or more of hydroxy, halogen, amino, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(C1-8 alkyl)(C1-8 alkyl), amino, —NH(C1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-8 alkyl)SO2(C1-8 alkyl), —SO2NHCO(C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), —SO(C1-8 alkyl) or —SO2(C1-8 alkyl);
or
(4) —OR8;
R4 is selected from
hydrogen, halogen, hydroxy, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(1-8 alkyl)(C1-8 alkyl), amino, —NH(1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-6 alkyl)SO2(C1-8 alkyl), —SO2NHCO(C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), —SO(C1-8 alkyl), —SO2(C1-8 alkyl), and Ar2;
X is N—R10, wherein R10 is C1-8 alkyl or an electron pair;
Y1 is —CR11R12—, —CR11R12(CH2)p—, or (CH2)pCR11R12—;
where p is 0, 1, or 2;
Y2 is —CR11R12—;
R11 and R12 are independently selected at each occurrence from:
(1) hydrogen, and
(2) C1-8 alkyl;
or
R10 and R11 may be joined to form a 5- to 8-membered ring which may contain one or more double bonds;
one O, S(O)n, or N—R7 wherein n and R7 are as defined above;
and which may be substituted with one or more of hydroxy, halogen, amino, C1-8 alkyl, —O(C1-8 alkyl), —NO2, —CN, —SO2NH2, —SO2NH(C1-8 alkyl), —SO2N(C1-8 alkyl)(C1-8 alkyl), amino, —NH(C1-8 alkyl), —N(C1-8 alkyl)(C1-8 alkyl), —N(C1-8 alkyl)CO(C1-8 alkyl), —N(C1-8 alkyl)CO2(C1-8 alkyl), —NHSO2(C1-8 alkyl), —N(C1-8 alkyl)SO2(C1-8 alkyl), —SO2NHCO(C1-8 alkyl), —CONHSO2(C1-8 alkyl), —CON(C1-8 alkyl)(C1-8 alkyl), —CO2(C1-8 alkyl), —S(C1-8 alkyl), and —SO(C1-8 alkyl).

42 more elements