Thio-substituted biarylmethanesulfinyl derivatives
View Patent ↗The present invention is related to chemical compositions, processes for the preparation thereof and uses of the composition. Particularly, the present invention relates to compositions that include substituted biaryl-methanesulfinyl acetamides of Formula (I): wherein Ar, Y, R 1 , R 2 , R 4 , R 5 , q and x are as defined herein; and their use in the treatment of diseases, including treatment of sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder; Parkinson's disease; Alzheimer's disease; attention deficit disorder; attention deficit hyperactivity disorder; depression; or fatigue associated with a neurological disease; as well as the promotion of wakefulness.
1. A method of treating sleepiness associated with narcolepsy, obstructive sleep apnea, or shift work disorder; Parkinson's disease; Alzheimer's disease; attention deficit disorder; attention deficit hyperactivity disorder; depression; or fatigue in a mammal comprising administering to said mammal a therapeutically effective amount of a compound of Formula (I):
or a stereoisomeric form, mixture of stereoisomeric forms or pharmaceutically acceptable salt form thereof,
wherein:
Ar is C 6 -C 10 aryl substituted by 0-5 R 3 ;
C 5 -C 10 cycloalkenyl substituted by 0-5 R 3 ; or
5 to 14 membered heteroaryl group substituted by 0-5 R 3 , wherein said heteroaryl group is selected from phenoxathiinyl, quinolinyl, isoxazolyl, thienyl, benzothienyl, (1,1-dioxo)-benzothienyl, indolyl, furyl, benzofuryl, pyridyl, seleninyl, 1,3-dihydro-isoindolyl, pyrrolyl, imidazopyridinyl, triazolyl, purine and 2-benzo[1,4]dioxine;
Y is C 1 -C 6 alkylene substituted with 0-3 R 20A ;
R 1 is selected from H, C(═O)NR 12 R 13 , C(═N)NR 12 R 13 , OC(═O)NR 12 R 13 , NR 21 C(═O)NR 12 R 13 , NR 21 S(═O) 2 NR 12 R 13 , —(C 6 -C 10 aryl)-NR 12 R 13 wherein said aryl is substituted with 0-3 R 20 ; NR 21 C(═O)R 14 , C(═O)R 14 , C(═O)OR 11 , OC(═O)R 11 , and NR 21 S(═O) 2 R 11 ;
R 2 is selected from H, F, Cl, Br, I, OR 16 , OR 25 , NR 17 R 18 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C(═O)R 16 , C(═O)OR 16 , OC(═O)R 16 , C(═O)NR 17 R 18 , NR 15 C(═O)R 16 , NR 15 CO 2 R 16 , OC(═O)NR 17 R 18 , NR 15 C(═S)R 16 , SR 16 , S(═O)R 16 , and S(═O) 2 R 16 ;
alternatively, two R 2 groups may be combined to form a methylenedioxy group, an ethylenedioxy group, or a propylenedioxy group;
R 3 is selected from H, F, Cl, Br, I, OR 16 , OCF 3 , OR 25 , NR 17 R 18 , NHOH, NO 2 , CN, CF 3 , CH 2 OR 16 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, phenyl, C 7 -C 10 arylalkyl, C(═O)R 16 , C(═O)OR 16 , OC(═O)R 16 , C(═O)NR 17 R 18 , NR 15 C(═O)R 16 , NR 15 CO 2 R 16 , OC(═O)NR 17 R 18 , NR 15 C(═S)R 16 , SR 16 , S(═O)R 16 , S(═O) 2 R 16 , and NR 15 S(═O) 2 R 16 ;
alternatively, two R 3 groups may be combined to form a methylenedioxy group, an ethylenedioxy group, or a propylenedioxy group;
R 4 and R 5 at each occurrence are independently selected from H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 2 -C 6 alkynyl;
alternatively, R 4 and R 5 , together with the carbon atom to which they are attached, form a 3-7 membered spirocyclic ring;
R 11 at each occurrence is independently selected from H, C 1 -C 6 alkyl substituted with 0-3 R 20 ; and C 6 -C 10 aryl substituted with 0-3 R 20 ;
R 12 and R 13 at each occurrence are each independently selected from H, C 1 -C 6 alkyl substituted with 0-3 R 20 ; and C 6 -C 10 aryl substituted with 0-3 R 20 ;
alternatively, R 12 and R 13 , together with the nitrogen to which they are attached, form a 3-7 membered heterocyclic ring substituted with 0-3 R 20 , wherein said heterocyclic ring is selected from piperazinyl, piperidinyl and pyrrolidinyl;
R 14 at each occurrence is independently selected from C 1 -C 6 alkyl substituted with 0-3 R 20 ; C 6 -C 10 aryl substituted with 0-3 R 20 ; and C 7 -C 10 arylalkyl substituted with 0-3 R 20 ;
R 15 at each occurrence is independently selected from H and C 1 -C 6 alkyl;
R 16 at each occurrence is independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl;
R 17 and R 18 at each occurrence are each independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl,
R 20 at each occurrence is independently selected from F, Cl, Br, I, OH, OR 22 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 1 -C 6 alkyl-OH, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, phenyl substituted by 0-1 R 26 ; C 7 -C 10 arylalkyl, ═O, C(═O)R 22 , C(═O)OR 22 , OC(═O)R 22 , C(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 CO 2 R 22 , OC(═O)NR 23 R 24 , NR 21 C(═S)R 22 , SR 22 , S(═O)R 22 , and S(═O) 2 R 22 ;
R 20A at each occurrence is independently selected from F, Cl, OH, C 1 -C 6 alkoxy, CF 3 , C 1 -C 6 alkyl, C 1 -C 6 alkyl-OH, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and C 3 -C 7 cycloalkyl;
R 21 at each occurrence is independently selected from H and C 1 -C 6 alkyl;
R 22 at each occurrence is independently selected from H, C 1 -C 6 alkyl, C 1 -C 6 alkyl-OH, and C 6 -C 10 aryl;
R 23 and R 24 at each occurrence are each independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl,
R 25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed;
R 26 at each occurrence is independently selected from H, F, Cl, Br, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;
x is 0, 1, 2, 3, or 4; and
q is 1, or 2;
provided
when Y is —CH 2 —, Ar is phenyl substituted by 0-5 R 3 , and —C(R 4 )(R 5 )— is —CH(C 1 -C 3 alkyl)-, then Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when Y is —CH 2 —, R 1 is H, C(═O)OR 11 , or C(═O)NR 12 R 13 ; Ar is phenyl substituted by 0-2 R 3 , and R 3 is H, F, Cl, Br, I, CH 3 , OCH 3 , SCH 3 , CN, NO 2 , or methylenedioxyphenyl; then Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when Ar is imidazopyridine substituted by 0-5 R 3 , Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when Ar is in the meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring and Ar is a heteroaryl group attached to the phenyl ring through a nitrogen atom, then Ar is pyrrolyl, indolyl, triazolyl, or 1,3-dihydroisoindolyl;
when Y is —CH 2 — and Ar is pyridyl substituted by a nitro, a methyl, a second methyl, and a C(═O)OC 3 H 7 group, then R 1 is not H;
when Y is —CH 2 — and Ar is a purine or imidazopyridine substituted by 0-5 R 3 , then R 1 is not H;
when q is 1, Y is butylene and Ar is phenyl, substituted by 0-5 R 3 , in the para position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring, then R 1 is not H;
when q is 1, Y is —CH 2 — or —CH 2 CH 2 —, and Ar is pyrrolyl in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring; then R 1 is not H;
when q is 1, R 2 is OH, and Ar is phenyl or cycloalkenyl; then R 1 is not H or C(═O)OR 11 ;
when q is 1, Y is —CH 2 —, R 4 is H, R 5 is H, and Ar is phenyl in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring, then R 1 is not H;
when q is 2, then Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when q is 2, Y is —CH 2 —, R 4 is H, R 5 is H, and Ar is 1,2-(methylenedioxy)-phenyl, then Ar is in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring; and
when q is 2, and Ar is phenyl in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring, then R 1 is not H.
2. The method of claim 1 , wherein the compound is administered for the treatment of sleepiness associated with narcolepsy.
3. A method for the promotion of wakefulness comprising administering a compound of Formula (I):
or a stereoisomeric form, mixture of stereoisomeric forms or pharmaceutically acceptable salt form thereof,
wherein:
Ar is C 6 -C 10 aryl substituted by 0-5 R 3 ;
C 5 -C 10 cycloalkenyl substituted by 0-5 R 3 ; or
5 to 14 membered heteroaryl group substituted by 0-5 R 3 , wherein said heteroaryl group is selected from phenoxathiinyl, quinolinyl, isoxazolyl, thienyl, benzothienyl, (1,1-dioxo)-benzothienyl, indolyl, furyl, benzofuryl, pyridyl, seleninyl, 1,3-dihydro-isoindolyl, pyrrolyl, imidazopyridinyl, triazolyl, purine and 2-benzo[1,4]dioxine;
Y is C 1 -C 6 alkylene substituted with 0-3 R 20A ;
R 1 is selected from H, C(═O)NR 12 R 13 , C(═N)NR 12 R 13 , OC(═O)NR 12 R 13 , NR 21 C(═O)NR 12 R 13 , NR 21 S(═O) 2 NR 12 R 13 , —(C 6 -C 10 aryl)-NR 12 R 13 wherein said aryl is substituted with 0-3 R 20 ; NR 21 C(═O)R 14 , C(═O)R 14 , C(═O)OR 11 , OC(═O)R 11 , and NR 21 S(═O) 2 R 11 ;
R 2 is selected from H, F, Cl, Br, I, OR 16 , OR 25 , NR 17 R 18 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C(═O)R 16 , C(═O)OR 16 , OC(═O)R 16 , C(═O)NR 17 R 18 , NR 15 C(═O)R 16 , NR 15 CO 2 R 16 , OC(═O)NR 17 R 18 , NR 15 C(═S)R 16 , SR 16 , S(═O)R 16 , and S(═O) 2 R 16 ;
alternatively, two R 2 groups may be combined to form a methylenedioxy group, an ethylenedioxy group, or a propylenedioxy group;
R 3 is selected from H, F, Cl, Br, I, OR 16 , OCF 3 , OR 25 , NR 17 R 18 , NHOH, NO 2 , CN, CF 3 , CH 2 OR 16 , C 1 -C 6 alkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, phenyl, C 7 -C 10 arylalkyl, C(═O)R 16 , C(═O)OR 16 , OC(═O)R 16 , C(═O)NR 17 R 18 , NR 15 C(═O)R 16 , NR 15 CO 2 R 16 , OC(═O)NR 17 R 18 , NR 15 C(═S)R 16 , SR 16 , S(═O)R 16 , S(═O) 2 R 16 , and NR 15 S(═O) 2 R 16 ;
alternatively, two R 3 groups may be combined to form a methylenedioxy group, an ethylenedioxy group, or a propylenedioxy group;
R 4 and R 5 at each occurrence are independently selected from H, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, and C 2 -C 6 alkynyl;
alternatively, R 4 and R 5 , together with the carbon atom to which they are attached, form a 3-7 membered spirocyclic ring;
R 11 at each occurrence is independently selected from H, C 1 -C 6 alkyl substituted with 0-3 R 20 ; and C 6 -C 10 aryl substituted with 0-3 R 20 ;
R 12 and R 13 at each occurrence are each independently selected from H, C 1 -C 6 alkyl substituted with 0-3 R 20 ; and C 6 -C 10 aryl substituted with 0-3 R 20 ;
alternatively, R 12 and R 13 , together with the nitrogen to which they are attached, form a 3-7 membered heterocyclic ring substituted with 0-3 R 20 , wherein said heterocyclic ring is selected from piperazinyl, piperidinyl and pyrrolidinyl;
R 14 at each occurrence is independently selected from C 1 -C 6 alkyl substituted with 0-3 R 20 ; C 6 -C 10 aryl substituted with 0-3 R 20 ; and C 7 -C 10 arylalkyl substituted with 0-3 R 20 ;
R 15 at each occurrence is independently selected from H and C 1 -C 6 alkyl;
R 16 at each occurrence is independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl;
R 17 and R 18 at each occurrence are each independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl,
R 20 at each occurrence is independently selected from F, Cl, Br, I, OH, OR 22 , OR 25 , NR 23 R 24 , NHOH, NO 2 , CN, CF 3 , C 1 -C 6 alkyl, C 1 -C 6 alkyl-OH, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, C 3 -C 7 cycloalkyl, phenyl substituted by 0-1 R 26 ; C 7 -C 10 arylalkyl, ═O, C(═O)R 22 , C(═O)OR 22 , OC(═O)R 22 , C(═O)NR 23 R 24 , NR 21 C(═O)R 22 , NR 21 CO 2 R 22 , OC(═O)NR 23 R 24 , NR 21 C(═S)R 22 , SR 22 , S(═O)R 22 , and S(═O) 2 R 22 ;
R 20A at each occurrence is independently selected from F, Cl, OH, C 1 -C 6 alkoxy, CF 3 , C 1 -C 6 alkyl, C 1 -C 6 alkyl-OH, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, and C 3 -C 7 cycloalkyl;
R 21 at each occurrence is independently selected from H and C 1 -C 6 alkyl;
R 22 at each occurrence is independently selected from H, C 1 -C 6 alkyl, C 1 -C 6 alkyl-OH, and C 6 -C 10 aryl;
R 23 and R 24 at each occurrence are each independently selected from H, C 1 -C 6 alkyl, and C 6 -C 10 aryl;
R 25 at each occurrence is independently the residue of an amino acid after the hydroxyl group of the carboxyl group is removed;
R 26 at each occurrence is independently selected from H, F, Cl, Br, C 1 -C 6 alkyl, and C 1 -C 6 alkoxy;
x is 0, 1, 2, 3, or 4; and
q is 1, or 2;
provided
when Y is —CH 2 —, Ar is phenyl substituted by 0-5 R 3 , and —C(R 4 )(R 5 )— is —CH(C 1 -C 3 alkyl)-, then Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when Y is —CH 2 —, R 1 is H, C(═O)OR 11 , or C(═O)NR 12 R 13 ; Ar is phenyl substituted by 0-2 R 3 , and R 3 is H, F, Cl, Br, I, CH 3 , OCH 3 , SCH 3 , CN, NO 2 , or methylenedioxyphenyl;
then Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when Ar is imidazopyridine substituted by 0-5 R 3 , Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when Ar is in the meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring and Ar is a heteroaryl group attached to the phenyl ring through a nitrogen atom, then Ar is pyrrolyl, indolyl, triazolyl, or 1,3-dihydroisoindolyl;
when Y is —CH 2 — and Ar is pyridyl substituted by a nitro, a methyl, a second methyl, and a C(═O)OC 3 H 7 group, then R 1 is not H;
when Y is —CH 2 — and Ar is a purine or imidazopyridine substituted by 0-5 R 3 , then R 1 is not H;
when q is 1, Y is butylene and Ar is phenyl, substituted by 0-5 R 3 , in the para position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring, then R 1 is not H;
when q is 1, Y is —CH 2 — or —CH 2 CH 2 —, and Ar is pyrrolyl in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring; then R 1 is not H;
when q is 1, R 2 is OH, and Ar is phenyl or cycloalkenyl; then R 1 is not H or C(═O)OR 11 ;
when q is 1, Y is —CH 2 —, R 4 is H, R 5 is H, and Ar is phenyl in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring, then R 1 is not H;
when q is 2, then Ar is in the ortho or meta position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring;
when q is 2, Y is —CH 2 —, R 4 is H, R 5 is H, and Ar is 1,2-(methylenedioxy)-phenyl,
then Ar is in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring; and
when q is 2, and Ar is phenyl in the ortho position to the —C(R 4 )(R 5 )— substituent on the core phenyl ring, then R 1 is not H.
4. The method of claim 1 or 3 wherein the compound of Formula I has the following structure:
and is selected from the following:
Ar
Ex. No.
Ar
Position
q
Y-R 1
1
3-thienyl
ortho
1
CH 2 CONH 2
2
3-thienyl
ortho
1
CH 2 CO-N-pyrrolidinyl
3
3-thienyl
ortho
1
CH 2 CON(CH 3 ) 2
4
3-thienyl
ortho
1
CH 2 CONHCH(CH 3 ) 2
5
3-thienyl
ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
6
3-thienyl
ortho
1
CH 2 CONH(CH 2 ) 2 OH
7
3-thienyl
ortho
1
CH 2 CO-1-(4-hydroxy)-piperidinyl
9
3-thienyl
ortho
1
CH 2 CO-1-(4-ethylcarboxamide)-
piperazinyl
10
3-thienyl
ortho
1
CH 2 CO-1-(4-carboxamide)-
piperazinyl
11
3-thienyl
ortho
1
CH 2 CO-1-(4-phenylcarboxamide)-
piperazinyl
12
3 -thienyl
ortho
1
CH 2 CO-N-piperazinyl
13
3-thienyl
ortho
1
CH 2 CO-1-(4-ethylcarboxylate)-
piperazinyl
14
3 -thienyl
ortho
1
CH 2 CO-1-(4-methyl)-piperazinyl
15
3-thienyl
ortho
1
CH 2 COOH
16
3-thienyl
ortho
2
CH 2 CO-1-(4-acetyl)-piperazinyl
17
5-chloro-
ortho
1
CH 2 CONH 2
2-thienyl
18
4-methyl-
ortho
1
CH 2 CONH 2
3-thienyl
19
3-thienyl
meta
1
CH 2 CONH 2
20
3-thienyl
meta
1
CH 2 CO-N-pyrrolidinyl
21
3-thienyl
meta
1
CH 2 CON(CH 3 ) 2
22
3-thienyl
meta
1
CH 2 CONHCH(CH 3 ) 2
23
3-thienyl
meta
1
CH 2 CO-1-(4-acetyl)-piperazinyl
24
3-thienyl
meta
1
CH 2 CONH(CH 2 ) 2 OH
25
3-thienyl
meta
1
CH 2 CO-1-(4-hydroxy)-piperidinyl
26
3-thienyl
meta
1
CH 2 CO-1-(4-phenyl)-piperazinyl
27
3-thienyl
meta
1
CH 2 CO-1-(4-ethylcarboxylate)-
piperazinyl
28
3-thienyl
meta
1
CH 2 CO-1-(4-methyl)-piperazinyl
29
3-thienyl
meta
1
CH 2 CO-N-piperazinyl
30
3-thienyl
meta
1
CH 2 CO-1-(4-carboxamide)-
piperazinyl
31
3-thienyl
meta
1
CH 2 CO-1-(4-propylphenyl)-
piperazinyl
32
3-thienyl
meta
1
CH 2 CO-1-(4-propyl)-piperazinyl
33
5-chloro-
meta
1
CH 2 CONH 2
2-thienyl
34
3-thienyl
para
1
CH 2 CO-N-pyrrolidinyl
35
3-thienyl
para
1
CH 2 CONH 2
36
3-thienyl
para
1
CH 2 CON(CH 3 ) 2
37
3-thienyl
para
1
CH 2 CONHCH(CH 3 ) 2
38
3-thienyl
para
1
CH 2 CONHCH 2 CN
39
3-thienyl
para
1
CH 2 CO-1-(4-acetyl)-piperazinyl
40
3-thienyl
para
1
CH 2 CO-1-(4-hydroxy)-piperidinyl
41
3-thienyl
para
1
CH 2 CO-1-(4-methyl)-piperazinyl
42
3-thienyl
para
1
CH 2 CO-1-(4-cyclohexyl)-piperazinyl
43
3 -thienyl
para
1
CH 2 CO-1-(4-ethylcarboxylate)-
piperazinyl
44
3-thienyl
para
1
CH 2 CO-1-(4-carboxamide)-
piperazinyl
45
3-thienyl
para
1
CH 2 CO-N-piperazinyl
46
3-thienyl
para
1
CH 2 CO-1-(4-ethylcarboxamide)-
piperazinyl
47
2-benzo-
ortho
1
CH 2 CONH 2
thienyl
48
2-benzo-
ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
thienyl
49
2-benzo-
ortho
1
CH 2 CO-1-(4-ethylcarboxylate)-
thienyl
piperazinyl
50
2-benzo-
ortho
1
CH 2 CO-N-piperazinyl
thienyl
51
2-benzo-
ortho
1
CH 2 CO-1-(4-carboxamide)-
thienyl
piperazinyl
52
2-benzo-
ortho
1
CH 2 CO-1-(4-ethylcarboxamide)-
thienyl
piperazinyl
53
2-benzo-
ortho
1
CH 2 CO-1-(4-phenylcarboxamide)-
thienyl
piperazinyl
55
2-benzo-
ortho
1
(CH 2 ) 2 CONH 2
thienyl
56
2-benzo-
ortho
1
(CH 2 ) 2 CO-1-(4-methyl)-piperazinyl
thienyl
57
2-benzo-
ortho
1
CH 2 COOH
thienyl
58
2-benzo-
ortho
2
CH 2 CONH 2
thienyl
59
2-(1,1-
ortho
2
CH 2 CONH 2
dioxo)-
benzo-
thienyl
60
2-benzo-
ortho
1
CH 2 CO-1-(4-methyl)-piperazinyl
thienyl
61
3-benzo-
ortho
1
CH 2 CONH 2
thienyl
63
3-benzo-
ortho
1
(CH 2 ) 2 CO-1-(4-methyl)-piperazinyl
thienyl
64
3-benzo-
ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
thienyl
65
3-benzo-
ortho
1
CH 2 CO-1-(4-ethylcarboxylate)-
thienyl
piperazinyl
66
3 -benzo-
ortho
1
CH 2 CO-1-(4-hydroxyethyl)-
thienyl
piperazinyl
67
2-benzo-
meta
1
CH 2 CONH 2
thienyl
68
2-benzo-
meta
1
CH 2 CO-1-(4-acetyl)-piperazinyl
thienyl
69
2-benzo-
meta
1
CH 2 CO-1-(4-methyl)-piperazinyl
thienyl
70
2-benzo-
meta
1
CH 2 CONHCH(CH 3 ) 2
thienyl
72
2-benzo-
meta
1
CH 2 CO-1-(4-ethylcarboxylate)-
thienyl
piperazinyl
73
2-benzo-
meta
1
CH 2 CON(C 2 H 5 ) 2
thienyl
74
2-benzo-
para
1
CH 2 CONH 2
thienyl
75
2-benzo-
para
1
CH 2 CO-1-(4-acetyl)-piperazinyl
thienyl
76
2-benzo-
meta
1
CH 2 CO-1-(4-hydroxyethyl)-
thienyl
piperazinyl
77
3 -benzo-
meta
1
CH 2 CONH 2
thienyl
78
3 -benzo-
meta
1
CH 2 CO-1-(4-acetyl)-piperazinyl
thienyl
79
3 -benzo-
meta
1
CH 2 CO-1-(4-methyl)-piperazinyl
thienyl
80
3 -benzo-
meta
1
CH 2 CO-1-(4-hydroxyethyl)-
thienyl
piperazinyl
81
3 -benzo-
meta
1
CH 2 CO-1-(4-ethylcarboxylate)-
thienyl
piperazinyl
82
2-benzo-
para
1
CH 2 CO-1-(4-methyl)-piperazinyl
thienyl
83
2-benzo-
para
1
CH 2 CO-1-(4-hydroxyethyl)-
thienyl
piperazinyl
84
3 -benzo-
para
1
CH 2 CONH 2
thienyl
85
2-indolyl
ortho
1
CH 2 CONH 2
86
3-furyl
ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
87
3-furyl
ortho
1
CH 2 CO-1-(4-methyl)-piperazinyl
88
3-furyl
ortho
1
CH 2 CONH 2
89
3-pyridyl
ortho
1
CH 2 CONH(isopropyl)
90
3-pyridyl
ortho
1
CH 2 CONH(CH 2 ) 2 OH
91
3-pyridyl
ortho
1
CH 2 CONH 2
92
3-pyridyl
ortho
1
CH 2 CONH 2
93
3-pyridyl
meta
1
CH 2 CONH 2
94
3-pyridyl
meta
1
CH 2 CO-1-(4-acety)piperazinyl
95
3-pyridyl
meta
1
CH 2 CONH(CH 2 ) 2 OH
96
3-pyridyl
meta
1
CH 2 CO-N-piperazinyl
97
3-pyridyl
meta
1
CH 2 CONH 2
98
3-pyridyl
para
1
CH 2 CONH 2
99
3-pyridyl
para
1
CH 2 CO-1-(4-acetyl)piperazinyl
100
3-pyridyl
para
1
CH 2 CO-N-piperazinyl
101
3-pyridyl
para
1
CH 2 CONH(CH 2 ) 2 OH
102
3-pyridyl
para
1
CH 2 CONH 2
103
2- furyl
ortho
1
CH 2 CON(CH 3 ) 2
104
2- furyl
ortho
1
CH 2 CONHCH 2 CN
105
2- furyl
ortho
1
CH 2 CONH(isopropyl)
106
2- furyl
ortho
1
CH 2 CONH 2
107
2- furyl
ortho
1
CH(OCH 3 )CONH 2
108
2- furyl
ortho
1
CH 2 CONH(CH 2 ) 2 OH
109
2- furyl
ortho
1
CH 2 CO-1-(4-acetyl)piperazinyl
110
2- furyl
ortho
1
CH 2 COOH
111
2-furyl
meta
1
CH 2 CO-N-pyrrolidinyl
112
2-furyl
meta
1
CH 2 CON(CH 3 ) 2
113
2-furyl
meta
1
CH 2 CONH(isopropyl)
114
2-furyl
meta
1
CH 2 CONHCH 2 CN
115
2-furyl
meta
1
CH 2 CO-1-(4-acetyl)piperazinyl
116
2-furyl
meta
1
CH 2 CONH(CH 2 ) 2 0H
117
2-furyl
meta
1
CH 2 CO-N- (4-piperidinol)
118
2-furyl
meta
1
CH 2 CO-N-piperazinyl
119
2-furyl
meta
1
CH 2 CONH 2
120
2-furyl
meta
1
CH 2 CO-1-[4-(2-methoxyphenyl)]-
piperazinyl
121
2-furyl
meta
1
CH 2 CO-1-[4-(4-fluorophenyl)]-
piperazinyl
122
2-furyl
meta
1
CH 2 CO-1-(4-phenyl)piperazinyl
123
2-furyl
meta
1
CH 2 CONH 2
124
2-sele-
meta
1
CH 2 CO-1-(4-acetyl)piperazinyl
ninyl[[1]]
125
2-hydroxy-
meta
1
CH 2 CO-1-(4-acetyl)piperazinyl
phenyl
126
2-benzo-
meta
1
CH 2 CO-1-(4-acetyl)piperazinyl
furyl
127
2-benzo-
meta
1
CH 2 CONH(CH 2 ) 2 OH
furyl
128
2- furyl
para
1
CH 2 CONH 2
129
2- furyl
para
1
CH 2 CONH(isopropyl)
130
2- furyl
para
1
CH 2 CONHCH 2 CN
131
2- furyl
para
1
CH 2 CON(CH 3 ) 2
132
2- furyl
para
1
CH 2 CO-1-(4-acetyl)piperazinyl
133
2- furyl
para
1
CH 2 CONH(CH 2 ) 2 OH
134
2- furyl
para
1
CH 2 CO-N-piperazinyl
135
2-thienyl
ortho
1
CH 2 CO-N-pyrrolidinyl
136
2-(5-
ortho
1
CH 2 CO-N-pyrrolidinyl
bromo)-
thienyl
137
2-thienyl
ortho
1
CH 2 CON(CH 3 ) 2
138
2-(5-
ortho
1
CH 2 CON(CH 3 ) 2
bromo)-
thienyl
139
2-thienyl
ortho
1
CH 2 CONH 2
140
2-thienyl
ortho
1
CH 2 CONH(CH 2 ) 2 OH
141
2-thienyl
ortho
1
CH 2 CO-N-piperazinyl
142
2-thienyl
ortho
1
CH 2 CO-1-(4-acetyl)piperazinyl
143
2-thienyl
ortho
1
CH 2 CONH(isopropyl)
144
2-thienyl
meta
1
CH 2 CO-N-pyrrolidinyl
145
2-thienyl
meta
1
CH 2 CON(CH 3 ) 2
146
2-thienyl
meta
1
CH 2 CONH 2
147
2-thienyl
meta
1
CH 2 CONH(CH 2 ) 2 OH
148
2-thienyl
meta
1
CH 2 CO-N-piperazinyl
149
2-thienyl
meta
1
CH 2 CO-1-(4-acetyl)piperazinyl
150
2-thienyl
para
1
CH 2 CO-N-pyrrolidinyl
151
2-(5-
para
1
CH 2 CO-N-pyrrolidinyl
bromo)-
thienyl
152
2-thienyl
para
1
CH 2 CON(CH 3 ) 2
153
2-(5-
para
1
CH 2 CON(CH 3 ) 2
bromo)-
thienyl
154
2-thienyl
para
1
CH 2 CONH 2
155
2-thienyl
para
1
CH 2 CONHCH 2 CN
156
2-thienyl
para
1
CH 2 CONH(isopropyl)
157
2-thienyl
para
1
CH 2 CO-1-(4-acetyl)piperazinyl
158
2-thienyl
para
1
CH 2 CONH(CH 2 ) 2 OH
159
2-thienyl
para
1
CH 2 CO-N-piperazinyl
436
2- furyl
ortho
2
CH 2 CO-1-(4-acetyl)piperazinyl
160
1,3-Dihydro-
ortho
1
CH 2 CO-N-pyrrolidinyl
isoindol-2-yl
161
1,3-Dihydro-
ortho
1
CH 2 CONMe 2
isoindol-2-yl
162
1,3-Dihydro-
meta
1
CH 2 CO-N-pyrrolidinyl
isoindol-2-yl
163
1,3-Dihydro-
meta
1
CH 2 CONMe 2
isoindol-2-yl
164
1,3-Dihydro-
meta
1
CH 2 CONHCHMe 2
isoindol-2-yl
165
1,3-Dihydro-
meta
1
CH 2 CONHCH 2CN
isoindol-2-yl
166
2-Benzofuryl
Ortho
1
CH 2 CO-1-piperazinyl
167
2-Benzofuryl
Ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
168
2-benzo-
Ortho
1
CH 2 CO-1-(4-acetyl)-piperazinyl
[1,4]dioxine
169
2-benzo-
Ortho
1
CH 2 CO-1-(4-methyl)-piperazinyl
[1,4]dioxine
170
2-benzo-
Ortho
1
CH 2 CONHCH(CH 3 ) 2
[1,4]dioxine
171
Pyrrol-1-yl
meta
1
CH 2 CONH(CH 2 ) 2 OH
172
Pyrrol-1-yl
meta
1
CH 2 CO-1-(4-hydroxy)-piperidinyl
173
Pyrrol-1-yl
meta
1
CH 2 CO-1-(4-acetyl)-piperazinyl
174
Pyrrol-1-yl
ortho
1
CH 2 CONH(CH 2 ) 2 OH
175
Pyrrol-1-yl
ortho
1
CH 2 CO-1-(4-hydroxy)-piperidinyl
176
Pyrrol-1-yl
ortho
1
CH 2 CONH(CH 2 ) 2 O(CH 2 ) 2 OH
177
Pyrrol-1-yl
ortho
1
CH 2 CO-N-pyrrolidinyl
178
Pyrrol-1-yl
ortho
1
CH 2 CONMe 2
179
Pyrrol-1-yl
ortho
1
CH 2 CONHCHMe 2
180
Pyrrol-1-yl
ortho
1
CH 2 CO-1-(4-acetyl)-
piperazinyl
181
Pyrrol-1-yl
meta
1
CH 2 CONHCH 2 CN
182
Pyrrol-1-yl
meta
1
CH 2 CONHCHMe 2
183
Pyrrol-1-yl
meta
1
CH 2 CONMe 2
184
2-Benzofuryl
Ortho
1
CH 2 CON(CH 3 ) 2
185
2-Benzofuryl
Ortho
1
CH 2 CONHCH(CH 3 ) 2
186
Pyrrol-1-yl
ortho
1
CH 2 CONH 2
187
Pyrrol-1-yl
meta
1
CH 2 CONH 2
188
Pyrrol-1-yl
para
1
CH 2 CONH 2
190
2-benzo[1,4]-
ortho
1
CH 2 CONH 2
dioxine
191
2-Benzofuryl
Ortho
1
CH 2 CONH 2
192
1,3-Dihydro-
ortho
1
CH 2 CONH 2
isoindol-2-yl
193
1,3-Dihydro-
meta
1
CH 2 CONH 2
isoindol-2-yl
194
phenyl
ortho
1
CH 2 CON(CH 3 ) 2
195
phenyl
ortho
1
CH 2 CONH 2
196
phenyl
ortho
1
CH 2 CONHCH 3
197
phenyl
ortho
1
CH 2 CON(C 2 H 5 ) 2
198
phenyl
ortho
1
CH 2 CONH(CH 2 ) 2 OH
199
phenyl
ortho
1
CH 2 CONHCH 2 -( 3 -
pyridyl)
200
phenyl
ortho
1
CH 2 CONH(cyclobutyl)
201
phenyl
ortho
1
CH 2 CONH-(cyclopentyl)
202
phenyl
ortho
1
CH 2 CO-N-pyrrolidinyl
203
phenyl
ortho
1
CH 2 CO-N-(2-carboxamide)-
pyrrolidinyl
205
phenyl
ortho
1
CH 2 CO-N-piperazinyl
206
phenyl
ortho
1
CH 2 CO-N-1-(4-t-
butylcarboxylate)-piperazinyl
207
phenyl
ortho
1
CH 2 CONHCH 2 CN
208
phenyl
ortho
1
CH 2 CO NHCH 2 CF 3
210
phenyl
ortho
1
CH 2 CONHCH(CH 3 ) 2
211
phenyl
para
1
CH 2 CO NH 2
212
phenyl
para
1
CH 2 CO-N-pyrrolidinyl
213
phenyl
para
1
CH 2 CO N(CH 3 ) 2
215
phenyl
Para
1
CH 2 CO-N-piperidinyl
216
phenyl
para
1
CH 2 CONH(CH 2 ) 2 -( 2 -
pyridyl)
217
phenyl
para
1
CH 2 CONHCH 2 -( 3 -
pyridyl)
218
phenyl
Para
1
CH 2 CONHCH(CH 3 ) 2
219
phenyl
Meta
1
CH 2 CONH 2
220
phenyl
Meta
1
CH 2 CON(CH 3 ) 2
221
phenyl
Meta
1
CH 2 CO-N-pyrrolidinyl
222
phenyl
Meta
1
CH 2 CONHCH(CH 3 ) 2
Ex. No.
Q
Ar
Y-R 1
Ar position
353
1
cyclohexen-1-yl
CH 2 CONH 2
ortho
354
1
cyclopenten-1-yl
CH 2 CONH 2
ortho
355
1
cyclohepten-1-yl
CH 2 CONH 2
ortho
356
1
Naphth-2-yl
CH 2 CONH 2
ortho
357
1
phenoxathiin-4-yl
CH 2 CONH 2
ortho
358
1
Quinolin-3-yl
CH 2 CONH 2
ortho
359
1
3,5-dimethyl-isoxazol-4-yl
CH 2 CONH 2
ortho
Ar
Ex. No.
q
Ar
position
Y-R 1
400
1
naphtha-2-yl
meta
CH 2 CONH 2
401
1
3,5-
meta
CH 2 CONH 2
dimethyl-isoxazol-
4-yl
Ar
Ex. No.
q
Ar
position
Y-R 1
430
1
(3,5-dimethyl)-
para
CH 2 CONH 2
isoxazol-4-yl
Ar
Ex. No.
Ar
Position
q
Y-R 1
431
2-benzothienyl
ortho
1
CH 3
432
3-thienyl
ortho
1
CH 3
433
2-furyl
para
1
CH 3
434
2-thienyl
para
1
CH 3
435
phenyl
ortho
1
CH 3
or a stereoisomeric form, mixture of stereoisomeric forms or a pharmaceutically acceptable salt thereof.
5. The method of claim 1 or 3 wherein the compound is 2-[2-(5-chloro-benzo[b]thiophen-2-yl)-phenylmethanesulfinyl]-acetamide, 2-(2-benzo[b]thiophen-5-yl-phenylmethanesulfinyl)-acetamide, 2-[2-(3-chloro-benzofuran-2-yl)-phenylmethanesulfinyl]-acetamide, or a stereoisomeric form, mixture of stereoisomeric forms or a pharmaceutically acceptable salt thereof or is a compound of selected from the following:
selected from
Ex. No.
Ar
437
4′-fluoro-3-benzothienyl
438
4′-fluoro-2-furyl
439
4′-fluoro-3-furyl
440
4′-fluoro-3-pyridyl
441
4′-fluoro-5-chloro-2-thienyl
442
5′-chloro-3-pyridyl
443
4′-fluoro-3-thienyl
444
4′-fluoro-5-chloro-2-benzothienyl
or a stereoisomeric form, mixture of stereoisomeric forms, or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 or 3 wherein the compound of Formula I has the following structure:
and is selected from the following:
Substitution on
Ex. No.
q
Biphenyl Moiety
Y-R 1
223
1
4′-COCH 3
CH 2 CONH 2
224
1
4′-F
CH 2 CONH 2
225
1
4′-CH3
CH 2 CONH 2
226
1
2′-CH3
CH 2 CONH 2
227
1
3′,5′-Difluoro
CH 2 CONH 2
228
1
3′,5′-Dimethyl
CH 2 CONH 2
229
1
3′-F
CH 2 CONH 2
230
1
2′-F
CH 2 CONH 2
231
1
2′-OEt
CH 2 CONH 2
232
1
3′-F,4′-Ph
CH 2 CONH 2
233
1
2′-OMe, 5′-F
CH 2 CONH 2
234
1
4′-OMe
CH 2 CONH 2
235
1
4′-OPh
CH 2 CONH 2
236
1
3′-CN
CH 2 CONH 2
237
1
3′CONH 2
CH 2 CONH 2
238
1
3′,5′-Dichloro
CH 2 CONH 2
239
1
3′-CF 3
CH 2 CONH 2
240
1
3′-SCH 3
CH 2 CONH 2
241
1
3′-SOMe
CH 2 CONH 2
242
1
3′-OCF 3
CH 2 CONH 2
243
1
3′-CONMe 2
CH 2 CONH 2
244
1
4′-OCF 3
CH 2 CONH 2
245
1
4 ′-CF 3
CH 2 CONH 2
246
1
4′-SCH 3
CH 2 CONH 2
247
1
4′-SOCH 3
CH 2 CONH 2
248
1
2′-Cl
CH 2 CONH 2
249
1
3′-Cl
CH 2 CONH 2
250
1
4′-Cl
CH 2 CONH 2
251
1
2′-OMe
CH 2 CONH 2
252
1
3′-OMe
CH 2 CONH 2
253
1
3′,4′-Dimethoxy
CH 2 CONH 2
254
1
3′,4′-Methylenedioxy
CH 2 CONH 2
255
1
3′,4 ′-Ethylenedioxy
CH 2 CONH 2
256
1
3′,4′-Propylenedioxy
CH 2 CONH 2
257
1
2′,6′-Dimethoxy
CH 2 CONH 2
258
1
2′,5′-Dimethoxy
CH 2 CONH 2
259
1
3′-NO 2
CH 2 CONH 2
260
1
2′-OH
CH 2 CONH 2
261
1
3′-OH
CH 2 CONH 2
262
1
4′-OH
CH 2 CONH 2
263
1
4′-CN
CH 2 CONH 2
264
1
3′-Me
CH 2 CONH 2
265
1
2′-OCF 3
CH 2 CONH 2
266
1
3′-Me, 4′-F
CH 2 CONH 2
267
1
2′-SMe
CH 2 CONH 2
268
1
3-Cl, 4′-F
CH 2 CONH 2
269
1
2′-OMe, 5′-Cl
CH 2 CONH 2
270
1
2′-SOMe
CH 2 CONH 2
271
1
4,5-(OMe) 2
CH 2 CONH 2
272
1
4′-Br
CH 2 CONH 2
273
1
2′-OMe, 4′-Cl
CH 2 CONH 2
274
1
2′-Me, 4′-Cl
CH 2 CONH 2
275
1
2′-Cl, 4′-Cl
CH 2 CONH 2
276
1
2′-CF 3
CH 2 CONH 2
277
1
2′-F, 4′-Br
CH 2 CONH 2
278
2
4′-Cl
CH 2 CONH 2
279
1
4′-CHMe 2
CH 2 CONH 2
280
1
4′-CMe 3
CH 2 CONH 2
281
2
4′-Me
CH 2 CONH 2
282
2
4′-F
CH 2 CONH 2
283
1
4′-Cl
(CH 2 ) 2 OH
284
1
3′-Br
CH 2 CONH 2
285
1
2′-Br
CH 2 CONH 2
286
1
4′-Cl
CH 2 CO-N-
pyrrolidinyl
287
1
4′-NMe 2
CH 2 CONH 2
288
1
4′-CH=CH 2
CH 2 CONH 2
289
1
4′-Cl
CH 2 CO-4-
acetylpiperazinyl
290
1
4′-SO 2 Me
CH 2 CONH 2
291
1
3′,4′-Cl 2
CH 2 CONH 2
292
1
4′-Et
CH 2 CONH 2
293
1
4′-CH 2 OMe
CH 2 CONH 2
294
1
4′-CO-N-(4-
CH 2 CONH 2
oxo)piperidinyl
295
1
4′-NHSO 2 Me
CH 2 CONH 2
296
1
4′-CONMe 2
CH 2 CONH 2
298
1
4′-Cyclohexyl
CH 2 CONH 2
299
1
3′,4′-F 2
CH 2 CONH 2
300
1
3′,4′,5′-OMe 3
CH 2 CONH 2
302
1
4′-Cl
(CH 2 ) 2 CONH 2
303
1
3′-NMe 2
CH 2 CONH 2
304
1
4′-CH 2 CHMe 2
CH 2 CONH 2
305
1
5-F, 4′-Cl
CH 2 CONH 2
306
1
3′-F, 4′-Cl
CH 2 CONH 2
307
1
5-F, 4′-Me
CH 2 CONH 2
308
1
5-F, 4′-F
CH 2 CONH 2
309
1
5-F, 4′-NMe 2
CH 2 CONH 2
310
1
3′-OMe, 4′-Cl
CH 2 CONH 2
311
1
3′,4′-F 2 , 5′-OMe
CH 2 CONH 2
312
1
3′-CF 3 , 4′-Cl
CH 2 CONH 2
313
1
4′-OCH 2 CHMe 2
CH 2 CONH 2
314
1
4′-COOMe
CH 2 CONH 2
315
1
4′-CH 2 OH
CH 2 CONH 2
316
1
4′-COOtBu
CH 2 CONH 2
317
1
3′,4′-Me 2
CH 2 CONH 2
318
1
3′-CF 3 , 4′-F
CH 2 CONH 2
319
1
3′-F, 4′-Me
CH 2 CONH 2
320
1
3′-Cl, 4′-Me
CH 2 CONH 2
321
1
3′-Me, 4′-Cl
CH 2 CONH 2
322
1
4,5-O-CH 2 -O, 4′-Cl
CH 2 CONH 2
323
1
4,5-OMe 2 , 4′-Cl
CH 2 CONH 2
324
1
4,5-O-CH 2 -O, 4′-F
CH 2 CONH 2
325
1
5-F, 3′, 4′-F 2
CH 2 CONH 2
326
1
4,5-O-CH 2 -O, 4′-Me
CH 2 CONH 2
327
1
4,5-O-CH 2 -O,
CH 2 CONH 2
3′, 4′-F 2
328
1
4,5-OMe 2 , 4′-F
CH 2 CONH 2
329
1
4,5-OMe 2 , 4′-Me
CH 2 CONH 2
330
1
4,5-OMe 2 , 3′, 4′-F 2
CH 2 CONH 2
331
1
3′-Me, 4′-OMe
CH 2 CONH 2
332
1
5-Cl, 4′-Cl
CH 2 CONH 2
333
1
3′,5′-Me 2 , 4′-Cl
CH 2 CONH 2
334
1
5-Cl, 4′-F
CH 2 CONH 2
335
1
3′-CF 3 , 4′-Me
CH 2 CONH 2
336
1
3′-NO 2 , 4′-Cl
CH 2 CONH 2
337
1
4-F, 4′-Cl
CH 2 CONH 2
338
1
5-Cl, 3′,4′-F 2
CH 2 CONH 2
339
2
5-F, 4′-Cl
CH 2 CONH 2
340
1
4′-F
(CH 2 ) 2 CONH 2
341
1
4-F, 4′-F
CH 2 CONH 2
342
1
4-F, 4′-Me
CH 2 CONH 2
343
1
4-F, 3′, 4′-F 2
CH 2 CONH 2
344
2
3′, 4′-F 2
CH 2 CONH 2
345
1
5-Cl, 4′-Me
CH 2 CONH 2
346
1
4-OMe, 4′-Cl
CH 2 CONH 2
347
1
6-Me, 4′-Cl
CH 2 CONH 2
348
1
6-Me, 3′,4′-Cl 2
CH 2 CONH 2
349
1
4-OMe, 3′,4′-Cl 2
CH 2 CONH 2
350
1
4-Cl, 4′-Cl
CH 2 CONH 2
351
1
4-F, 3′,4′-Cl 2
CH 2 CONH 2
352
1
6-Me, 3′-F, 4′-Cl
CH 2 CONH 2
402
1
3-F
CH 2 CONH 2
403
1
2′-Cl
CH 2 CONH 2
404
1
3′-Cl
CH 2 CONH 2
405
1
4′-OMe
CH 2 CONH 2
406
1
3′,4′-Methylenedioxy
CH 2 CONH 2
407
1
2′,6′-(OMe) 2
CH 2 CONH 2
408
1
4′-Cl
CH 2 CONH 2
409
1
3′,4′-(OMe) 2
CH 2 CONH 2
410
1
3′-OMe
CH 2 CONH 2
411
1
4′-CN
CH 2 CONH 2
412
1
2′,5′-(OMe) 2
CH 2 CONH 2
413
1
3′-NO 2
CH 2 CONH 2
414
1
3′-Me
CH 2 CONH 2
415
1
2′-OMe
CH 2 CONH 2
416
1
2′-Me, 4′-Cl
CH 2 CONH 2
417
1
2′-OMe, 4′-Cl
CH 2 CONH 2
418
1
2′, 4′-Cl 2
CH 2 CONH 2
419
2
3′,4′-(OMe) 2
CH 2 CONH 2
420
1
3′,4′-Cl 2
CH 2 CONH 2
421
1
3-F, 4′-Cl
CH 2 CONH 2
422
1
3-F, 4′-Me
CH 2 CONH 2
423
1
4′-Br
CH 2 CONH 2
424
1
3′-Cl, 4′-OMe
CH 2 CONH 2
425
1
3′,4′,5′-(OMe) 3
CH 2 CONH 2
426
1
3′,4′-F 2
CH 2 CONH 2
427
1
3-F, 4′-F
CH 2 CONH 2
428
2
3-F, 4′-F
CH 2 CONH 2
429
1
3-F, 4′-Cl
CH 2 CONH 2
402
1
3-F
CH 2 CONH 2
403
1
2′-Cl
CH 2 CONH 2
404
1
3′-Cl
CH 2 CONH 2
405
1
4′-OMe
CH 2 CONH 2
406
1
3′,4′-Methylenedioxy
CH 2 CONH 2
407
1
2′,6′-(OMe) 2
CH 2 CONH 2
408
1
4′-Cl
CH 2 CONH 2
409
1
3′,4′-(OMe) 2
CH 2 CONH 2
410
1
3′-OMe
CH 2 CONH 2
411
1
4′-CN
CH 2 CONH 2
412
1
2′,5′-(OMe) 2
CH 2 CONH 2
413
1
3′-NO 2
CH 2 CONH 2
414
1
3′-Me
CH 2 CONH 2
415
1
2′-OMe
CH 2 CONH 2
416
1
2′-Me, 4′-Cl
CH 2 CONH 2
417
1
2′-OMe, 4′-Cl
CH 2 CONH 2
418
1
2′, 4′-Cl 2
CH 2 CONH 2
419
2
3′,4′-(OMe) 2
CH 2 CONH 2
420
1
3′,4′-Cl 2
CH 2 CONH 2
421
1
3-F, 4′-Cl
CH 2 CONH 2
422
1
3-F, 4′-Me
CH 2 CONH 2
423
1
4′-Br
CH 2 CONH 2
424
1
3′-Cl, 4′-OMe
CH 2 CONH 2
425
1
3′,4′,5′-(OMe) 3
CH 2 CONH 2
426
1
3′,4′-F 2
CH 2 CONH 2
427
1
3-F, 4′-F
CH 2 CONH 2
428
2
3-F, 4′-F
CH 2 CONH 2
429
1
3-F, 4′-Cl
CH 2 CONH 2
or a stereoisomeric form, mixture of stereoisomeric forms, or a pharmaceutically acceptable salt thereof.