Useful indole compounds
Indoles having various activities, including indoles that are CRTH2 are described. The compounds are useful for treating asthma, neuropathic pain, allegic rhinitis and other disorders.
1 . A compound having Formula I
wherein
R 1 is H or a halogen;
R 2 is OH, a halogen, -CH 3 , wherein any carbon can be optionally, independently substituted with one or more halogen; or -OCH 3 , wherein any carbon can be optionally, independently substituted with one or more halogen;
R 3 is a halogen or -CH 3 ;
R 8 is H or Cl;
R 6 is independently selected from F, Cl, Br, -CH 3 , CF 3 , -OCH 3 , OCF 2 H, -OCFH 2 , -OCF 3 -CN, -SCF 3 , -SCH 3 , CF 2 H, or -SCF 2 H;
m is 1 , 2 , or 3 .
R 9 is -CH 2 CH 3 or -CH 3 ;
n= 1 , 2 , or 3 ;
R 5 is -CH 3 or H, wherein when n= 2 or 3 , R 5 is independently -CH 3 or H; and A is -OH, -OCH 3 , OCH 2 CH 3 , -OCH 2 CH 2 CH 3 , or -OCH 2 CH 2 CH 2 CH 3 ;
2 . The compound of claim 1 wherein
3 . The compound of claim 1 wherein:
-CH 2 CH 2 C(O)OH, -CH 2 C(O)OH,-CH 2 CH 2 C(O)OCH 3 ,-CH 2 C(O)OCH 3 , -CH 2 CH 2 C(O) OCH 2 CH 3 , CH 2 C(O)OCH 2 CH 3 , -CH 2 CH 2 C(O)OCH 2 CH 2 CH 3 ,or -CH 2 C(O)OCH 2 CH 2 CH 3 .
4 . The compound of claim 1 wherein
-CH(CH 2 )C(O)OH, -CH(CH 2 )C(O)OCH 3 , -CH(CH 2 )CH 2 C(O) OH, -CH(CH 2 ) CH 2 C(O)OCH 3 , -CH(CH 2 )C(O)OCH 2 CH 3 , or -CH(CH 2 )CH 2 C(O)OCH 2 CH 3 .
5 - 7 . (canceled)
8 . The compound of claim 7 wherein R 9 is -CH 3 .
9 . (canceled)
10 . The compound of any of claim 1 wherein R 2 is F, Cl, -OCH 3 or -CH 3 .
11 . The compound of claim 10 where R 2 is -OCH 3 or -CH 3 .
12 . The compound of claim 11 wherein R 2 is -OCH 3 .
13 . The compound of claim 11 wherein R 2 is -CH 3 .
14 . The compound of claim 1 wherein R 2 is -OCH 3 singly or independently multiply substituted with one or more halogen or -CH 3 singly or independently multiply substituted with one or more halogen.
15 . The compound of claim 1 wherein R 2 is -OH.
16 . The compound of claim 1 wherein R 3 is a halogen.
17 . The compound of claim 16 wherein R 3 is F, Cl, or Br.
18 . The compound claim 17 wherein R 3 is Cl.
19 . The compound claim 17 wherein R 3 is Br.
20 . The compound claim 17 wherein R 3 is F.
21 . The compound of any of claim 1 wherein R 8 is H.
22 . The compound of claim 1 wherein
m= 1 , 2 , or 3 and each R 6 is independently a halogen, -SCF 3 , -SCH 3 , -CF 3 , -OCF 3 or -OCH 3 .
23 . The compound of claim 1 wherein R 6 is -SCF 3 .
24 . The compound of claim 1 wherein R 6 is -SCH 3 .
25 . The compound of claim 1 wherein R 6 is -CF 3 .
26 . The compound of claim 1 wherein R 6 is -OCF 3 .
27 . The compound of claim 1 wherein R 6 is -OCH 3 .
28 . The compound of claim 1 wherein R 6 is a halogen.
29 . The compound of claim 28 wherein R 6 is Cl.
30 . The compound of claim 28 wherein R 6 is F.
31 . The compound of claim 1 wherein
32 . (canceled)
33 . The compound of claim 1 wherein
m is 2 or 3 and at least one R 6 is in the meta position.
34 . The compound of claim 1 wherein
35 . The compound of claim 1 wherein
m is 1 and R 6 is in the ortho or para position.
36 . The compound of claim 1 wherein R 1 and R 8 are H.
37 . The compound of claim 1 wherein
is -CH 2 C(O)OH.
38 . (canceled)
39 . The compound of claim 1 having the formula;
40 . The compound of claim 39 wherein R 6 is: -CH 3 , -CF 3 , -OCH 3 , OCF 2 H, -OCFH 2 , -OCF 3 , -CN, -SCF 3 , -SCH 3 , -CF 2 H.
41 . The compound of claim 40 wherein R 6 is: -OCH 3 , -OCF 2 H, -OCFH 2 , or -OCF 3 , -CN, SCF 3 , SCH 3 , -CF 2 H, or -SCF 2 H.
42 . The compound of claim 41 wherein R 6 is: -OCH 3 , -OCF 2 H, -OCFH 2 , or -OCF 3 .
43 . The compound of claim 39 wherein R 2 is H, F, Cl, -CH 3 , optionally, independently substituted with one or more halogen, or -OCH 3 , optionally, independently substituted with one or more halogen.
44 - 94 . (canceled)
95 . A method for treating asthma comprising administering the compound of any of claim 1 .
96 . A method for treating neuropathic pain comprising administering the compound of claim 1 .
97 . A method for treating allergic rhinitis comprising administering the compound of claim 1 .
98 - 100 . (canceled)
101 . A compound having Formula I:
wherein
R 1 is: H or a halogen;
R 2 is: H, a halogen, C 1 to C 6 alkyl, or R 2B O- wherein
R 2B is selected from:
(a) H;
(b) C 1 to C 6 alkenyl that is optionally independently substituted with one or more halogen; -OH, -NH 2 , -C(O)OH;
(c)
wherein each R 2A is independently: H a C 1 to C 6 alkyl, a C 2 to C 6 alkenyl, a C 2 to C 6 alkynl, a C 6 to C 10 aryl, a C 3 to C 10 cycloalkyl, or a C 7 to C 20 arylalkyl optionally independently substituted with one or more halogen, -OH, -C(O)OH, or -NH 2 ;
R 3 is H, a halogen, -CH 3 , -CF 3 , -CF 2 H, -OCF 2 H, -OCF 3 , -SCF 2 H, -SCF 3 or -CN;
Z is selected from;
wherein the carbonyl carbon is bonded to the N of the indole,
(e) C 1 to C 4 alkyl
wherein the carbonyl carbon is bonded to the N of the indole and q is 1 , 2 , 3 , or 4 ,
wherein the carbonyl carbon is bonded to the N of the indole,
wherein the carbonyl carbon is bonded to the N of the indole,
wherein the carbonyl carbon is bonded to the N of the indole, or
(j) a bond
A is selected from:
(a) -X 1 R 4 ,
(b) -X 2 ,
(d) a C 1 to C 6 alkyl, independently substituted with one or more halogen
(e) -C(O)OX 5 wherein X 5 is a C 1 to C 6 alkyl or alkenyl, independently substituted with one or more halogen; and
(f) -C(O)NH 2 ;
wherein
X 1 is -O-, -S-, -N(H)-or-N(H)S(O 2 )-;
R 4 is H; -OH, a C 1 to C 10 alkoxy, a C 1 to C 10 alkyl; a C 2 to C 10 alkenyl; a C 2 to C 10 alkynyl; a C 3 to C 8 cycoalkyl; a C 1 to C 6 hydroxyalkyl; a hydroxyl substituted C 6 to C 8 aryl; a primary, secondary or tertiary C 1 to C 6 alkylamino; primary, secondary or tertiary C 6 to C 8 arylamino; C 2 to C 6 alkylcarboxylic acid; a C 1 to C 6 alkylester; a C 6 to C 10 aryl; a C 6 to C 10 arylcarboxylic acid; a C 6 to C 10 arylester; a C 6 to C 10 aryl substituted C 1 to C 6 alkyl; a 4 to 8 membered unsaturated or saturated heterocycle or a 4 to 8 membered heteroaryl wherein the heteroatoms are selected from O, S, S( 0 ) 2 , N, and S(O); an alkyl-substituted or aryl-substituted 4 to 8 membered or or saturated heterocycle or 4 to 8 membered heteroaryl wherein the heteroatoms are selected from O, S, S(O) 2 N, and S(O), wherein one or more H within R 4 can be replaced by a halogen, -OH, or -C(O)OH, or -NH 2 ;
X 2 is;
(a) a benzyl group;
(b) a 6- membered unsaturated heterocycle having 1, 2, 3 or 4 heteroatoms independently selected from N, O and S;
(c) a 5- membered unsaturated heterocycle having 1, 2, 3 or 4 heteroatoms independently selected from N, O and S;
(d) a 5, 5 or 6, 5 unsaturated or aromatic fused ring having 1, 2, 3 or 4 heteroatoms independently selected from N, O and S;
(e) -C(O)OH,
(f) a C 1 -C 4 alkyl,
(g) a C 1 -C 4 alkoxyl, and
(h) a C 1 -C 4 thioalkoxy that;
wherein X 2 can be independently singly or multiply substituted at any substitutable position with OH, -CN, lower alkyl, lower alkoxy, halogen, and -CH 3 , -SCH 3 , -OCH 3 , -CH 2 CH 3 , -OCH 2 CH 3 , or -SCH 2 CH 3 , wherein one or more H can be replaced by a halogen.
Y is C or N;
Q os O or S;
X 3 and X 4 are independently selected from H, -C(O)H, -C(O)OH, a C 1 to C 6 alkyl a benzyl, a 6-membered unsaturated or aromatic heterocycle having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and a 5-membered unsaturated or aromatic heterocycle having 1, 2, or 3 heteroatoms independently selected from N, O, and S;
provided that when Y is N, X 3 is absent; n is 1 , 2 , 3 , 4 , or 5 ;
each R 5 is independently: H, -OH, halogen, or an optionally substituted C 1 to C 4 alkyl wherein the substituents are independently selected from a halogen and -OH;
represents a C 3 to C 6 saturated carbocycle; a C 6 aryl, C 3 C 6 non-saturated, non-aromatic carbocycle; a 6-membered heteroaryl having 1, 2, 3, 4 or 5 heteroatoms independently selected from O, S, S(O) 2 , N, S(O) and N (R 7 ); a 3- to 7 -membered saturated or non-saturated heterocycle having 1 , 2 , 3 , 4 or 5 heteroatoms independently selected from O, S, S(O) 2 , N, S(O) and N(R 7 ); a 6, 5-fused heteroaromatic ring system having 1, 2, 3 or 4 heteroatoms independently selected from N, O and S; a 6, 6-fused heteroaromatic ring system having 1, 2, 3 or 4 heteroatoms independently selected from N, O and S; a napthyl group;
each R 6 is independently H, -OH, a halogen, a C 1 -C 6 alkyl, -CN, -OCH 3 , -SCH 3 , -OCH 2 CH 3 , -SCH 2 CH 3 , -CH 2 CH 3 , -C(O)OCH 3 , -C(O)OH, a C 3 -C 6 alkoxy, a C 3 to C 6 saturated carbocycle, a C 6 aryl, C 3 - C 6 non-saturated , non-aromatic carbocycle, a 6-membered heteroaryl having 1, 2, 3, 4 or 5 heteroatoms independently selected from O, S, S(O) 2 , N, S(O) and N(R 7 ), a 3- to 7-membered saturated or non-saturated heterocycle having 1, 2, 3, 4 or 5 heteroatoms independently selected from O, S S(O) 2 , N, S(O) and N(R 7 ) wherein one or more H within R 6 can be replaced by a halogen;
m=1, 2, 3, 4, or 5;
R 7 is: H, a halogen, -CH 3 , -CN, -OCH 3 , -SCH 3 , -SCH 2 CH 3 , -OCH 2 CH 3 , -CH 2 CH 3 , or or a C 3 -C 6 alkoxy wherein one or more H can be replaced by a halogen;
R 8 is H, a halogen or -CH 3 , wherein one or more H can be replaced by a halogen; and
R 9 is Cl or a C 1 to C 6 alkyl, wherein one or more H can be replaced by a halogen.
102 - 222 . (canceled)
223 . A compound having Formula III
wherein
R 11 is selected from H, CH 3 , F, Cl, Br, -OH, -CF 3 ,CF 2 H, -OCH 3 , -OCF 2 H, -OCF 3 , SCH 3 , -SCF 2 H, -SCF 3 , -CN, -NO 2 , -SO 2 CH 3 , -SOCH 3 , SO 2 NH 2 ;
R 12 is selected from H, F, Cl, Br, -CH 3 , -OCH 3 , -CF 3 , CF 2 H, -ICF 2 H, -OCF 3 , SCH 3 ,-SCF 2 H, -SCF 3 , -CN, -SOCH 3 , -SO 2 CH 3 , -SO 2 NH 2 ; and
(a) R 13 is -C(O)OH; R 14 is H; and R 15 is H;
(b) R 13 is H; R 14 is -C(O)OH; and R 15 is H;
(c) R 13 is H; R 14 is H; and R 15 is -C(O)OH;
(d) R 13 is H; R 14 is -C(O)OH; and R 15 is -C(O)OH;
(e) R 13 is -C(O)OH; R 14 is H; and R 15 is -C(O)OH; or
(d) R 13 is selected from: H, C 1 -C 6 alkyl, -C(O)OH, and -PO(OH) 2 : R 14 is selected from H, C 1 -C 6 alkyl, -C(O)OH, and -PO(OH) 2 ; and R 15 is selected from -CH 2 PO(OH) 2 , -CH 2 CH 2 PO(OH) 2 , H, CH 3 , -CH 2 CO 2 H, -CH 2 CH 2 CO 2 H.
224 . A compound having Formula II
wherein
R 1 is: H or a halogen;
R 2 is: H, a halogen, C 1 to C 6 alkyl, or R 2B O- wherein
R 2B is selected from:
(a) H;
(b) C 1 to C 6 alkyl or a C 2 to C 6 alkenyl that is optionally independently substituted with one or more halogen; -OH, -NH 2 , -C(O)OH;
(c)
wherein each R 2A is independently: H, a C 1 to C 6 alkyl, a C 2 to C 6 alkenyl, a C 2 to C 6 alkenyl, a C 2 to C 6 alkynyl, a C 6 to C 10 aryl, a C 3 to C 10 cycloalkyl, or a C 7 to C 20 arylalkyl optionally independently substituted with one or more halogen, -OH, -C(O)OH, or -NH 2 ;
R 3 is H, a halogen, -CH 3 , -CF 3 , CF 2 H, OCF 2 H, -OCF 3 , -SCF 2 H, -SCF 3 or -CN
Z is selected from
wherein the carbonyl carbon is bonded to the N of the indole,
(e) C 1 to C 4 alkyl
wherein the the carbonyl carbon is bonded to the N of the indole and q is 1, 2, 3, or 4,
wherein the carbonyl carbon is bonded to the N of the indole,
wherein the carbonyl carbon is bonded to the N of the indole,
wherein the carbonyl carbon is bonded to the N of the indole, or
a bond
A is selected from:
(a) -X 1 R 4 ,
(b) -X 2 ,
(d) a C 1 to C 6 alkyl or alkenyl, independently substituted with one or more halogen,
(e) -C(O)PX 5 wherein X 5 is a C 1 to C 6 alkyl or alkenyl, independently substituted with one or more halogen; and
(f) -C(O)NH 2 ;
wherein:
X 1 is -O-, -S-, -N(H)- or -N(H)S(O 2 )-;
R 4 is H; -OH, a C 1 to C 10 alkoxy, a C 1 to C 10 alkyl; a C 2 to C 10 alkenyl; a C 2 to C 10 alkynyl; a C 3 to C 8 cycloalkyl; a C 1 to C 6 hydroxyalkyl; a hydroxyl substituted C 6 to C 8 aryl; a primary, secondary or tertiary C 1 to C 6 alkylamino; primary secondary or tertiary C 6 to C 8 arylamino; C 2 to C 6 alkylcarboxylic acid; a C 1 to C 6 alkylester; a C 6 to C 10 aryl; a C 6 to C 10 arylcarboxylic acid; a C 6 to C 10 arylester; a C 6 to C 10 aryl substituted C 1 to C 6 alkyl; a 4 to 8 membered unsaturated or saturated heterocycle or a 4 to 8 membered heteroaryl wherein the heteroatoms are selected from O, S, S(O) 2 , N, and S(O); an alkyl-substituted or aryl substituted 4 to 8 membered or saturated heterocycle pr 4 to 8 membered heteroaryl wherein the heteroatoms are selected from O, S, S(O) 2 , N, and S(O), wherein one or more H within R 4 can be replaced by a halogen, -OH, or -C(O)OH, or -NH 2 ;
(a) a benzyl group
(b) a 6-membered unsaturated heterocycle having 1, 2, 3 or 4 heteroatoms independently selected from N, O, and S;
(c) a 5-membered unsaturated heterocycle having 1, 2, 3 or 4 heteroatoms independently selected from N, O and S;
(d) a 5, 5 or 6, 5 unsaturated or aromatic fused ring having 1, 2, 3, or 4 heteroatoms independently selected from N, O, and S;
(e) -C(O)OH,
(f) a C 1 -C 4 alkyl, and
(g) a C 1 -C 4 alkoxyl, and
(h) a C 1 -C 4 thioalkoxy that;
wherein X 2 can be independently singly or multiply substituted at any substitutable position with OH, -CN, lower alkyl, lower alkoxy, halogen, and -CH 3 , -SCH 3 , -OCH 3 , -CH 2 CH 3 , -OCH 2 CH 3 , or -SCH 2 CH 3 , wherein one or more H can be replaced by a halogen.
Y is C or N;
Q is O or S;
X 3 and X 4 are independently selected from H, -C(O)H, -C(O)OH, a C 1 to 6 6 alkyl, a benzyl, a 6-membered unsaturated or aromatic heterocycle having 1, 2, or 3 heteroatoms independently selected from N, O, and S, and a 5-membered unsaturated or aromatic heterocycle having 1, 2, or 3 heteroatoms independently selected from N, O and S;
provided that when Y is N, X 3 is absent;
n is 1, 2, 3, 4 or 5
each R 5 is independently: H, -OH, halogen, or an optionally substituted C 1 to C 4 alkyl, wherein the substituents are independently selected from a halogen and -OH;
represents: a C 3 to C 6 saturated carbocycle; a C 6 aryl, C 3 to C 6 non-saturated, non-aromatic carbocycle; a 6- membered heteroaryl having 1, 2, 3, 4 or 5 heteroatoms independently selected from O, S, S(O) 2 , N, S(O) and N(R 7 ); a 3- to 7-membered saturated or non-saturated heterocycle having 1, 2, 3, 4 or 5 heteroatoms independently selected from O, S, S(O) 2 , N, S(O) and N(R 7 ); a 6, 5-fused heteroaromatic ring system having 1, 2, 3 or 4 heteroatoms independently selected from N, O and S; a 6, 6-fused heteroaromatic ring system having 1, 2, 3 or 4 heteroatoms independently selected from N, O and S; a napthyl group;
each R 6 is independently; H, -OH, a halogen, a C 1 -C 6 alkyl, -CN, -OCH 3 , -SCH 3 , -OCH 2 CH 3 , -SCH 2 CH 3 , -CH 2 CH 3 , -SO 2 CH 3 , -C(O)OCH 3 , -C(O)OH, a C 3 -C 6 alkoxy, a C 3 to C 6 saturated carbocycle, a C 6 aryl, C 3 -C 6 non-saturated, non-aromatic carbocycle, a 6-membered heteroaryl having 1, 2, 3, 4 or 5 heteroatoms independently selected from O, S, S(O) 2 , N, S(O) and N(R 7 ), a 3- to 7-membered saturated or non-saturated heterocycle having 1, 2, 3, 4 or 5 heteroatoms independently selected from O, S, S(O) 2 , N, S(O) and N(R 7 ) wherein one or more H can be replaced by a halogen;
m=1, 2, 3, 4, or 5;
R 7 is: H, a halogen, -CH 3 , -CN, -OCH 3 , -SCH 3 , -SCH 2 CH 3 , -OCH 2 CH 3 , -CH 2 CH 3 or or a C 3 - C 6 alkoxy wherein one or more H can be replaced by a halogen;
R 8 is: H, a halogen or -CH 3 , wherein one or more H can be replaced by a halogen; and
R 9 is Cl or a C 1 to C 6 alkyl, wherein one or more H can be replaced by a halogen.
225 - 245 . (canceled)
246 . A compound having Formula I
wherein
R 1 is H or a halogen;
R 2 is H, -OH, a halogen, CH 3 , wherein any carbon can be optionally, independently substituted with one or more halogen; or -OCH 3 , wherein any carbon can be optionally, independently substituted with one or more halogen;
R 3 is H, a halogen or CH 3 ;
Z is
-CH(CH 2 )- or CH 2 ;
R 8 is H or Cl;
R 6 is F, Cl, Br, -CH 3 , -CF 3 , -OCH 3 , -OCF 2 H, -OCF 3 , -CN, -SCF 3 , -SCH 3 , -CF 2 H, or -SCF 2 H;
m is 0, 1 2 or 3.
R 9 is H, a halogen, -CH 2 CH 3 or -CH 3 ;
n=1, 2, or 3
R 5 is -CH 3 or H, wherein when n=2 or 3, R 5 is independently -CH 3 or H; and A is selected from -OH, -OCH 3 , -OCH 2 CH 3 , -OCH 2 CH 2 CH 3 , -OCH 2 CH 2 CH 2 CH 3 ;;
provided that when
is -CH 2 C(O)OCH 3 ,
Z is CH 2 , R 1 is H, R 2 is -OCH 3 , R 3 is Cl, and R 9 is not Br or H;
further provided that when
Z is CH 2 , R 1 is H, R 2 is H, R 3 is -CH 3 , R 8 is H, and R 9 is -CH 3 ,
is not -CH 2 C(O)OCH 3 or -CH 2 C(O)OH;
further provided that when
Z is CH 2 , R 1 is H, R 2 is H, R 3 Cl, and R 8 is H, and R 9 is -CH 3 ,
is not -CH 2 C(O)OCH 3 ; and
further provided that when
R 1 is H, R 2 is H,R 3 -CH 3 , R 8 is H, and R 9 is -CH 3 ,
is not -CH 2 C(O)OH; and
further provided that when
R 1 is -CH 3 , R 2 is -OCH 3 , R 3 -CH 3 , R 8 is H, and R 9 is -CH 3 ,
is not -CH 2 C(O)OH; and
further provided that when
Z is CH 2 , R 1 is H, R 2 is F, R 3 H, R 8 is H, and R 9 is -CH 3 ,
is not -CH 2 C(O)OH.
247 - 288 . (canceled)
289 . A compound having the formula:
wherein
R 16 is H or Cl;
R 17 is H, F, Cl, -CH 3 , -OH, -OCH 3 or -OCF 3 ;
R 18 is H, F, Cl, or CH 3 ;
Z is
or CH 2 ;
R 19 is H or Cl;
R 21 is H, F, Cl, Br, -CH 3 , -CF 3 , -OCH 3 , -OCF 2 H, -OCG 3 or -CN;
m is 0, 1 or 2 and
R 20 is H, Cl, or CH 3 ,
provided that when Z is CH 2, R 20 is CH 3 , and
R 16 , R 17 , R 18 and R 19 are not all H;
further provided that when Z is CH 2 , R 20 is CH 3 ,
and R 17 is -OCH 3 , R 16 , R 18 and R 19 are not all H;
further provided that when Z is CH 2 , R 20 is Cl,
and R 17 is -CH 3 , R 16 , R 18 and R 19 are not all H;
further provided that when Z is CH 2 , R 20 is Cl,
and R 16 , R 17 , R 18 and R 19 are not all H;
further provided that when Z is CH 2 , and
R 16 , R 17 , R 18 and R 19 are not all H.
290 - 305 . (canceled)
306 . A compound A having the formula
wherein
Z is
or CH 2 ;
R 22 is -CH 3 , Cl or H;
R 23 is -OCH 3 , -CH 3 , -NH 2 , -C(O)OH, - C(O)OCH 3 , -C(O)NH 2 , CF 3 ,
R 23A is H, halogen, C 1 -C 6 alkoxy, -NO 2 , -CH 3 , CF 3 , -OCF 2 H, -OCF 3 , -CH 3 , -SCF 3 ,
wherein any substitutable position within a ring can be singly or multiply, independently substituted by halogen, C 1 -C 6 alkoxy, -CN, -CF 3 or NO 2 ,
R 24 is H or Cl;
R 25 is H, F, Cl, -OCH 3 , -CH 3 , OH, -OCF 3 ;
R 26 is H, F, Cl, or -CH 3 ;
R 27 is H;
R 28 is H, halogen, C 1 -C 6 alkoxy, -NO 2 , -CH 3 , -OCF 2 H, -OCF 3 , -CN, -SCH 3 , or -SCF 3
307 . The compound of claim 306 wherein R 23 is -OCH 3 , -CH 3 , -NH 2 , -C(O)NH 2 , -CF 3 ,
308 - 314 . (canceled)
315 . A compound having the formula
wherein
Z is
or CH 2 ;
R 22 is -CH 3 , Cl or H;
R 23 is -OCH 3 , CH 3 , -NH 2 , -C(O)OH, -C(O)OCH 3 , C(O)NH 2 , -CF 3 ,
R 23A is H, halogen, C 1 -C 6 alkoxy, -NO 2 , -CH 3 , CF 3 , -OCF 2 H, -OCF 3 , -CH 3 , -SCF 3 ,
wherein any substitutable position within a ring can be singly or multiply, independently substituted by halogen, C 1 -C 6 alkoxy, -CN, -CF 3 or NO 2 .
R 24 is H or Cl;
R 25 is H, F, Cl, -OCH 3 , -CH 3 , OH, -OCF 3 ;
R 26 is H, F, Cl or -CH 3 ;
R 27 is H;
R 28 is H, halogen, C 1 -C 6 alkoxy, -NO 2 , -CH 3 , -OCF 2 H, -OCF 3 , -CN, -SCH 3 , or -SCF 3 .
316 - 322 . (canceled)
323 . A compound having the formula
wherein
R 30 is H;
R 31 is O, H, -C(O)OH, halogen, -CH 2 C(O)OH, a C 1 -C 4 alkyl or alkenyl that is optionally substituted with a phenyl group, -OCH 2 C(O)OH, -SCH 2 C(O)OH, -OH, -N(H)CH 2 C(O)OH, -B(OH) 2 , -SO 3 H, -PO 3 H 2 , -CH 2 OH,
R 32 is H, a C 1 -C 4 alkyl or alkenyl that is optionally substituted with a phenyl group, halogen, -OH, -OCH 3 , -NH 2 , -SH, and -SCH 3 ;
R 33 and R 36 are independently selected from: H, a C 1 -C 4 alkyl or alkenyl that is optionally substituted with a phenyl group, -(CH 2 ) n C(O)C 6 H 5 wherein n is 1, 2, 3, or 4; -O(CH 2 ) n C 6 H 5 wherein n is 1, 2, 3, or 4, -S(CH 2 ) n C 6 H 5 wherein n is 1, 2, 3 or 4, -NH(CH 2 ) n C 6 H 5 wherein n is 1, 2, 3 or 4, -C(O)C 6 H 5 , -N(CH 3 )C(O)(CH 2 ) n C 6 H 5 wherein n is 1, 2, 3 or 4, -(CH 2 ) n OC 6 H 5 wherein n is 1, 2, 3 or 4, -(CH 2 ) n SC 6 H 5 wherein n is 1, 2, 3 or 4, -(CH 2 ) n S(O) m C 6 H 5 wherein m is 1 or 2, -(CH 2 ) n N(H)C 6 5 , -(CH 2 ) n N(CH 3 )C(O)C 6 H 5 , C 6 H 5 , halogen, -OH, -OCH 3 , -CH 2 OH; and
R 34 and R 35 are independently selected from H, C 1 -C 3 alkyl or alkenyl, halogen, -OH, -OCH 3 , -NH 2 ;-SH;
wherein any phenyl group can be optionally independently substituted with 1, 2, 3, of 4 substituents selected from -OCH 3 , OCF 2 H, -OCF 3 , a C 1 -C 4 alkyl, -CN, SCH 3 , -SCF 2 H, -SCF 3 , -CF 3 , and -CF 2 H, and wherein R 32 is O, represents a single bond and when R 32 is other than O, represents a double bond.
324 . A compound having the formula
wherein
R 37 is H, -C 1 -C 4 alkyl, -(CH 2 ) n OC 6 H 5 , -(CH 2 ) n N(H)C 6 H 5 , -(CH 2 ) n C 5 H 5 , wherein n is 1, 2, 3 or 4;
R 38 is O, H, -C(O)OH, halogen, -CH 2 C(O)OH, a C 1 -C 4 alkyl or alkenyl, -OCH 2 C(O)OH, -SCH 2 C(O)OH, -OH, -N(H)CH 2 C(O)OH, -B(OH) 2 , -SO 3 H, -PO 3 H 2 , -CH 2 OH,
R 39 is H, -C(O)OH, halogen, -CH 2 C(O)OH, a C 1 -C 4 alkyl or alkenyl, -OCH 2 C(O)OH, -SCH 2 C(O)OH, -OH, -OH, -N(H)CH 2 C(O)OH, -B(OH) 2 , -SO 3 H, -PO 3 H 2 , -CH 2 OH, -C(O)OCH 3 , -C(O)OCH 2 CH 3 ,
R 40 and R 43 are independently selected from: H, a C 1 -C 4 alkyl or alkenyl, -(CH 2 ) n C(O)C 6 H 5 wherein n is 1, 2, 3, or 4; -O(CH 2 ) n C 6 H 5 wherein n is 1 , 2 , 3 , or 4, -S(CH 2 ) n C 6 H 5 wherein n is 1, 2, 3 or 4, -NH(CH 2 ) n C 6 H 5 wherein n is 1 , 2 , 3 or 4, -C(O)C 6 H 5 , -N(CH 3 )C(O)(CH 2 ) n C 6 H 5 wherein n is 1, 2, 3 or 4, -(CH 2 ) n OC 6 H 5 wherein n is 1, 2, 3 or 4, -(CH 2 ) n N(H)C 6 H 5 , -(CH 2 ) n N(CH 3 )C(O)C 6 H 5 , C 6 H 5 , halogen, -OH, -OCH 3 , -CH 2 OH; and
R 41 and R 42 are independently selected from: H, C 1 -C 4 alkyl or alkenyl, halogen, -OH, -OCH 3 , -NH 2 , -SH;
wherein any phenyl group can be optionally independently substituted with 1, 2, 3 of 4 substituents selected from -OCH 3 , -OCF 2 H, -OCF 3 , a C 1 -C 4 alkyl, -CN, -SCH 3 , SCF 2 H, -SCF 3 , -CF 3 , and CF 2 H,
wherein where R 38 is O, represents a single bond and when R 38 is other than O, represents a double bond.
325 . A compound having the formula
wherein
represents a single or a double bond
R 45 is H, -C(O)OH, a halogen, -CH 2 C(O)OH, a C 1 -C 4 alkyl or alkenyl optional substituted with a phenyl group, -OCH 2 C(O)OH, O,-OH
-NHCH 2 C(O)H, B(OH) 2 , -SO 3 H, -PO 3 2 , -CH 2 OH,
R 46 is H, a C 1 -C 3 , alkyl or alkenyl, a C 1 -C 4 alkyl or alkenyl optional substituted with a
R 47 , R 48 are independently selected from: H, a C 1 -C 4 alkyl or alkenyl optional substituted with a phenyl group, -O(CH 2 ) n C 6 H 5 wherein n is 1 , 2 , 3 , or 4, -S(CH 2 ) n C 6 H 5 wherein n is 1, 2, 3 or 4, -NH(CH 2 ) n C 6 H 5 wherein n is 1 , 2 , 3 or 4, -C(O)C 6 H 5 , -N(CH 3 )C(O)(CH 2 ) n C 6 H 5 wherein n is 1, 2, 3 or 4, -(CH 2 ) n OC 6 H 5 wherein n is 1, 2, 3 or 4, -(CH 2 ) n SC 6 H 5 wherein n is 1, 2, 3 or 4, -(CH 2 ) n S(O) m C 6 H 5 wherein m is 1 or 2 and l is 1, 2, 3 or 4, -(CH 2 ) n N(H)C 6 H 5 , -(CH 2 ) n N(CH 3 )C(O)C 6 H 5 , a phenyl group, halogen, -OH, -OCH 3 , -CH 2 OH;
R 49 , R 50 and R 51 are independently selected from H, C 1 -C 3 alkyl or alkenyl, a halogen, OH, -OCH 3 , -NH 2 , -SH; wherein when R 45 is O, R 44 is H and
represents a single bond and when R 45 is other than O represents a double bond, and wherein wherein any phenyl group can be optionally independently substituted with 1, 2, 3 of 4 substituents selected from -OCH 3 , -OCF 2 H, -OCF 3 , a C 1 -C 4 alkyl, -CN, -SCH 3 , SCF 2 H, -SCF 3 , -CF 3 , and -CF 2 H.
326 . The compound of claim 1 wherein m is 2.