US2002111369A1PendingUtilityA1
Aryl sulfonic acids and derivatives as FSH antagonists
Est. expiryMar 31, 2019(expired)· nominal 20-yr term from priority
C07C 311/29A61P 15/18C07C 309/51C07C 317/44C07C 309/76C07C 317/48C07D 295/13A61P 15/16C07D 295/26
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Claims
Abstract
This invention provides compounds of formula I having the structure wherein Q is hydrogen or —SO 2 R 1 ; X is a bond, O, S(O) n , —CH═CH—, —CH 2 CH 2 —, —C≡C—, or —CH 2 S(O) n CH 2 —; R 1 is OH, NH 2 , C 1 to C 6 alkoxy, C 1 to C 3 perfluoroalkoxy; R 2 and R 4 are each, independently, hydrogen, OR 6 , —S(O) m R 6 , —NHR 6 , —N(R 6 ) 2 , or —CH 2 SO 2 CH 3 ; R 3 and R 5 are each, independently, hydrogen, —NO 2 , —NH 2 , —SO 2 R 9 , or —CH 2 R 9 ; R 6 is hydrogen, C 1 to C 6 alkyl, C 3 to C 6 alkenyl, —CH 2 CH 2 Z, —CH 2 COR 7 , —CH 2 CH═CHCOR 7 Y 1 and Y 3 are each, independently, N, or CH; Y 2 and Y 4 are each independently, O, S, or NR 13 ; R 7 is —OR 8 , —NHR 8 , —N(R 8 ) 2 , or —NHCH 2 CH 2 OR 8 ; Z is —OR 8 , —OCH 2 CH 2 OR 8 , —N(R 8 ) 2 , or R 8 is hydrogen, or C 1 to C 3 alkyl; R 9 is C 1 to C 6 alkyl, C 3 to C 6 alkenyl, OH, NHR 10 , N(R 10 ) 2 , CH 2 COR 11 , —CH 2 CH═CHCOR 11 , or R 10 is C 1 to C 3 alkyl, C 3 to C 4 alkenyl, phenyl, —CH 2 CH 2 OCH 3 , or R 11 is —OR 12 , NHR 12 , —N(R 12 ) 2 , or —NHCH 2 CH 2 OR 12 ; R 12 is hydrogen, or C 1 to C 3 alkyl; R 13 is hydrogen, or C 1 to C 3 alkyl; W is a bond, CH 2 , CH 2 CH 2 , O, S(O) q , NCHO, NCOCH 3 , or NR 12 ; m is 0-2; n is 0-2; q is 0-2, with the proviso that R 2 and R 3 are not both hydrogen; or pharmaceutically acceptable salt thereof, which are useful as contraceptive agents.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A compound of formula I having the structure
wherein
Q is hydrogen or —SO 2 R 1 ;
X is a bond, O, S(O) n , —CH═CH—, —CH 2 CH 2 —, —C≡C—, or —CH 2 S(O) n CH 2 —;
R 1 is OH, NH 2 , C 1 to C 6 alkoxy, C 1 to C 3 perfluoroalkoxy;
R 2 and R 4 are each, independently, hydrogen, OR 6 , —S(O) m R 6 , —NHR 6 , —N(R 6 ) 2 , or —CH 2 SO 2 CH 3 ;
R 3 and R 5 are each, independently, hydrogen, —NO 2 , —NH 2 , —SO 2 R 9 , or —CH 2 R 9 ;
R 6 is hydrogen, C 1 to C 6 alkyl, C 3 to C 6 alkenyl, —CH 2 CH 2 Z, —CH 2 COR 7 , —CH 2 CH═CHCOR 7
Y 1 and Y 3 are each, independently, N, or CH;
Y 2 and Y 4 are each independently, O, S, or NR 13 ;
R 7 is —OR 8 , —NHR 8 , —N(R 8 ) 2 , or —NHCH 2 CH 2 OR 8 ;
Z is —OR 8 , —OCH 2 CH 2 OR 8 , —N(R 8 ) 2 , or
R 8 is hydrogen, or C 1 to C 3 alkyl;
R 9 is C 1 to C 6 alkyl, C 3 to C 6 alkenyl, OH, NHR 10 , N(R 10 ) 2 , CH 2 COR 11 , —CH 2 CH═CHCOR 11 , or
R 10 is C 1 to C 3 alkyl, C 3 to C 4 alkenyl, phenyl, —CH 2 CH 2 OCH 3 , or
R 11 is —OR 12 , NHR 12 , —N(R 12 ) 2 , or —NHCH 2 CH 2 OR 12 ;
R 12 is hydrogen, or C 1 to C 3 alkyl;
R 13 is hydrogen, or C 1 to C 3 alkyl;
W is a bond, CH 2 , CH 2 CH 2 , O, S(O) q , NCHO, NCOCH 3 , or NR 12 ;
m is 0-2;
n is 0-2;
q is 0-2,
with the proviso that R 2 and R 3 are not both hydrogen;
or pharmaceutically acceptable salt thereof.
2 . The compound according to claim 1 , wherein
X is a bond, S(O) n , —CH═CH—, —CH 2 CH 2 —, or —CH 2 S(O) n CH 2 —; R 1 is OH, or C 1 to C 6 alkoxy; R 2 and R 4 are each, independently, hydrogen, OR 6 , —S(O) m R 6 , —NHR 6 , or —N(R 6 ) 2 ; Y 1 and Y 3 are CH; Z is —OR 8 or —OCH 2 CH 2 OR 8 ; R 9 is NHR 10 , N(R 10 ) 2 , CH 2 COR 11 , —CH 2 CH═CHCOR 11 , or R 10 is C 1 to C 3 alkyl, C 3 to C 4 alkenyl, —CH 2 CH 2 OCH 3 , or W is a bond, CH 2 , CH 2 CH 2 , O, S(O) q , NCHO, or NCOCH 3 ; or a pharmaceutically acceptable salt thereof.
3 . A compound of claim 1 , which is 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(methylthio)-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid] or a pharmaceutically acceptable salt thereof.
4 . A compound of claim 1 , which is 2,2′-[(E)-1,2-ethenediyl]bis[5-[[3-(4-morpholinylsulfonyl)-4-[(tetrahydro-2H-pyran-4-yl)oxy]benzoyl]amino]benzenesulfonic acid] or a pharmaceutically acceptable salt thereof.
5 . A compound of claim 1 , which is 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(methylsulfonyl)-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid] or a pharmaceutically acceptable salt thereof.
6 . A compound of claim 1 , which is 2,2′-[(E)-1,2-ethenediyl]bis[5-[[3-[(4-formyl-1-piperazinyl)sulfonyl)-4-methoxybenzoyl]amino]benzenesulfonic acid] or a pharmaceutically acceptable salt thereof.
7 . A compound of claim 1 , which is 2,2′-[(E)-1,2-ethenediyl]bis[5-[[3-[(1,1-dioxido-4-thiomorpholinyl)sulfonyl]-4-methoxybenzoyl]amino]benzenesulfonic acid] or a pharmaceutically acceptable salt thereof.
8 . A compound of claim 1 , which is 4,4′-bis[4-methoxy-3-(morpholine-4-sulfonyl)benzoylamino]biphenyl-2,2′-(bis)sulfonic acid or a pharmaceutically acceptable salt thereof.
9 . A compound of claim 1 , which is 2,2′-thiobis[5-[[4-methoxy-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid] or a pharmaceutically acceptable salt thereof.
10 . A compound of claim 1 , which is 2,2′-[thiobis(methylene)]bis[5-[[4-methoxy-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid] or a pharmaceutically acceptable salt thereof.
11 . A compound of claim 1 , which is 2,2′-[(E)-1,2-ethenediyl]bis[5-[[[5-(methylsulfonyl)2-thienyl]carbonyl]amino]benzenesulfonic acid] or a pharmaceutically acceptable salt thereof.
12 . A compound of claim 1 , which is 5-[[4-[[2-[(2-hydroxyethyl)amino]-2-oxoethyl]sulfonyl]benzoyl]amino]-2-[(E)-2-[4-[[4-[[2-[(2-hydroxyethyl)amino]-2-oxoethyl]sulfonyl]benzoyl]amino]-2-sulfo-phenyl]ethenyl]benzenesulfonic acid or a pharmaceutically acceptable salt thereof.
13 . A compound of claim 1 , which is 5-[4-methylsulfanyl-3-(morpholine-4-sulfonyl)-benzoylamino]-2-(2-{[4-methylsulfanyl-3-(morpholine-4-sulfonyl)-benzoylamino]-phenyl}-vinyl)-benzenesulfonic acid or a pharmaceutically acceptable salt thereof.
14 . A compound of claim 1 , which is
a) 2,2-[(E)-1,2-ethenediyl]bis[5-[[4-(methylthio)-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid], bis(1-methylethyl) ester; b) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(2-methoxyethoxy)-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid; c) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-[2-(2-methoxyethoxy)ethylthio]-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; d) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(methylsulfonyl)-3-nitrobenzoyl]amino]benzenesulfonic acid]; e) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(methylsulfonyl)-3-nitrobenzoyl]amino]benzenesulfonic acid], bis(1-methylethyl) ester; f) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-[2-(2-methoxyethoxy)ethoxy]-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; g) 2,2′-[(E)-1,2-ethenediyl]bis [5-[[4-methoxy-3-[[[2-(4-morpholinyl)ethyl]amino]sulfonyl]benzoyl]amino]benzenesulfonic acid]; h) 5-[[4-methoxy-3-(4-morpholinylsulfonyl)benzoyl]amino]-2-[(E)-2-[4-[[4-(methylsulfonyl)benzoyl]amino]-2-sulfophenyl]ethenyl]benzenesulfonic acid]; i) 5-[[4-methoxy-3-[[(2-methoxyethyl)amino]sulfonyl]benzoyl]amino]-2-[(E)-2-[4-[[4-(methylsulfonyl)-3-nitrobenzoyl]amino]-2-sulfophenyl]ethenyl]benzenesulfonic acid]; j) 5-[[4-methoxy-3-(4-morpholinylsulfonyl)benzoyl]amino]-2-[2-[4-[[4-(methylsulfonyl)benzoyl]amino]-2-sulfophenyl]ethyl]benzenesulfonic acid]; k) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-methoxy-3-[[(2-methoxyethyl)amino]sulfonyl]benzoyl]amino]benzenesulfonic acid]; l) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[3-[[bis(2-methoxyethyl)amino]sulfonyl]-4-methoxybenzoyl]amino]benzenesulfonic acid]; m) 2,2′-[(E)-1,2-ethanediyl]bis[5-[[4-methoxy-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; n) 5-[[4-(methylsulfonyl)-3-nitrobenzoyl]amino]-2-[(E)-2-[4-[[4-(methylthio)-3-(4-morpholinylsulfonyl)benzoyl]amino]-2-sulfophenyl]ethenyl]benzenesulfonic acid]; o) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(ethylsulfonyl)benzoyl]amino]benzenesulfonic acid]; p) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(ethylsulfonyl)benzoyl]amino]benzenesulfonic acid], bis(1-methylethyl) ester; q) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(methoxy)-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; r) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(2-propenylsulfonyl)benzoyl]amino]benzenesulfonic acid]; s) 2,2′-[(E)-1,2-ethenediyl]bis [5-[[4-(ethylthio)-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; t) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[3-[(4-acetyl-1-piperazinyl)sulfonyl]-4-methoxybenzoyl]amino]benzenesulfonic acid; u) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-[(2-ethoxyethyl)amino]-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; v) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(methylsulfonyl)benzoyl]amino]benzenesulfonic acid]; w) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[3-amino-4-(methylsulfonyl)benzoyl]amino]benzenesulfonic acid]; x) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-[(2-methoxyethyl)thio]-3-(4-morpholiylsulfonyl)benzoyl]amino]benzenesulfonic acid]; y) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-methoxy-3-(1-pyrrolidinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; z) 2,2′-[(E)-1,2-ethanediyl]bis[5-[[4-(methylsulfonyl)benzoyl]amino]benzenesulfonic acid]; aa) 2,2 ′-[(E)-1,2-ethanediyl]bis[5-[[3-[(1,1-dioxido-4-thiomorpholinyl)sulfonyl]-4-methoxybenzoyl]amino]benzenesulfonic acid]; bb) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[3-(4-morpholinylmethyl)benzoyl]amino]benzenesulfonic acid]; cc) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(dimethylamino)-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; dd) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-[bis(2-methoxyethyl)amino]-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; ee) 2,2′-(1,2-ethanediyl)bis[5-[[4-(2-methoxyethoxy)-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; ff) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-methoxy-3-(4-thiomorpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; gg) 5-[[4-(methylsulfonyl)benzoyl]amino]-2-[(E)-2-[4-[[4-[(methylsulfonyl)methyl]benzoyl]amino]-2-sulfophenyl]ethenyl]benzenesulfonic acid; hh) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-[(methylsulfonyl)methyl]benzoyl]amino]benzenesulfonic acid]; ii) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[3-[(diethylamino)sulfonyl]-4-methoxybenzoyl]amino]benzenesulfonic acid]; jj) 5-[[4-(2-methoxyethoxy)benzoyl]amino]-2-[(E)-2-[4-[[4-(methylsulfonyl)benzoyl]amino]-2-sulfophenyl]ethenyl]benzenesulfonic acid; kk) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid; ii) 5-[[4-(2-methoxyethoxy)benzoyl]amino]-2-[(E)-2-[4-[[4-methoxy-3-(4-morpholinylsulfonyl)benzoyl]amino]-2-sulfo-phenyl]ethenyl]benzenesulfonic acid; mm) 2,2′-[1,2-ethanediyl]bis[5-[[4-methoxy-3-(1-pyrrolidinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; nn) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(4-morpholinyl)-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; oo) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-methoxy-3-(1-piperidinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; pp) 5-[[4-(2-methoxyethoxy)benzoyl]amino]-2-[2-[4-[[4-methoxy-3-(4-morpholinylsulfonyl)benzoyl]amino]-2-sulfophenyl]ethyl]benzenesulfonic acid; qq) 2,2′-(-1,2-ethanediyl)bis[5-[[3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; rr) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[3-[(hexahydro-1H-azepin-1-yl)sulfonyl]-4-methoxybenzoyl]amino]benzenesulfonic acid]; ss) 2,2′-(1,2-ethanediyl)bis[5-[[4-methoxy-3-(1-piperidinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; tt) 2,2′-[sulfonylbis(methylene)]bis [5-[[4-methoxy-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; uu) [4-(4-{2-[4-(4-methoxycarbonylmethanesulfonyl-benzoylamino)-2-sulfo-phenyl]-vinyl}-3-sulfo-phenylcarbomoyl)-benzenesulfonyl]-acetic acid, methyl ester; vv) [4-(4-{2-[4-(4-carboxymethanesufonyl-benzoylamino)-2-sulfo-phenyl]-vinyl-)-3-sulfo-phenylcarbamoyl)-benzenesulfonyl]-acetic acid; ww) 5-[[4-[(2-amino-2-oxoethyl)sulfonyl]benzoyl]amino]-2-[(E)-2-[4-[[4-[(2-amino-2-oxoethyl)sulfonyl]benzoyl]amino]-2-sulfophenyl]ethenyl]-benzenesulfonic acid; xx) [3-(4-{2-[4-(3-methoxycarbonylmethanesulfonyl-benzoylamino)-2-sulfo-phenyl]-vinyl}-3-sulfo-phenylcarbomoyl)-benzenesulfonyl]-acetic acid, methyl ester; yy) 4-{3-[4-(2-{4-{3-(3-methoxycarbonyl-prop-2-ene-1-sulfonyl)-benzoylamino]-2-sulfo-phenyl}-vinyl)-3-sulfo-phenylcarbomoyl]-benzenesulfonyl}-but-2-enoic acid, methyl ester; zz) [3-(4-{2-[4-(3-carboxymethanesulfonyl-benzoylamino)-2-sulfo-phenyl]-vinyl}-3-sulfo-phenylcarbamoyl)-benzenesulfonyl]-acetic acid (WAY-163437); aaa) [4-[4-(2-{4-[4-methoxycarbonylmethylsulfanyl-3-(morpholine-4-sulfonyl)-benzoylamino]-2-sulfo-phenyl}-(E)-vinyl)-3-sulfo-phenylcarbamoyl]-2-(morpholine-4-sulfonyl)-phenylsulfanyl]-acetic acid, methyl ester; bbb) 4-{3-[4-(2-{4-[3-(3-carboxy-prop-2-ene-1-sulfonyl)-benzoylamino]-2-sulfo-phenyl}-vinyl)-3-sulfo-phenylcarbomoyl]-benzenesulfonyl}-but-2-enoic acid; ccc) 5-[[3-[(2-amino-2-oxoethyl)sulfonyl]benzoyl]amino]-2-[(E)-2-[4-[[3-[(2-amino-2-oxoethyl)sulfonyl]benzoyl]amino]-2-sulfophenyl]ethenyl]-benzenesulfonic acid; ddd) 5-[[3-[[2-[(2-hydroxyethyl)amino]-2-oxoethyl]sulfonyl]benzoyl]amino]-2-[(E)-2-[4-[[3-[[2-[(2-hydroxyethyl)amino]-2-oxoethyl]sulfonyl]benzoyl]amino]-2-sulfo-phenyl]ethenyl]benzenesulfonic acid eee) 2,2′-(1,2-ethanediyl)bis[5-[[4-(tetrahydro-2-furanmethyl)-3-(4-morpholinylsulfonyl)benzoyl]amino]benzenesulfonic acid]; fff) 2,2′-[(E)-1,2-ethenediyl]bis[5-[[4-(2-furanylmethoxy)-3-(4-morpholinylsulfony)benzoyl]amino]benzenesulfonic acid]; or ggg) N-[3-(aminosulfonyl)-4-[(E)-2-[2-(aminosulfonyl-4-[[4-(methylsulfanyl)-3-(4-morpholinyl-sulfonyl)benzoyl]amino]phenyl]ethenyl]phenyl]-4-(methylsulfanyl)-3-(4-morpholinylsulfonyl)benzamide; or a pharmaceutically acceptable salt thereof.
15 . A method of providing contraception in a female mammal in need thereof which comprises administering to said mammal a contraceptive effective amount of a compound of formula I having the structure
wherein
Q is hydrogen or —SO 2 R 1 ;
X is a bond, O, S(O) n , —CH═CH—, —CH 2 CH 2 —, —C≡C—, or —CH 2 S(O) n CH 2 —;
R 1 is OH, NH 2 , C 1 to C 6 alkoxy, C 1 to C 3 perfluoroalkoxy;
R 2 and R 4 are each, independently, hydrogen, OR 6 , —S(O) m R 6 , —NHR 6 , —N(R 6 ) 2 , or —CH 2 SO 2 CH 3 ;
R 3 and R 5 are each, independently, hydrogen, —NO 2 , —NH 2 , —SO 2 R 9 , or —CH 2 R 9 ;
R 6 is hydrogen, C 1 to C 6 alkyl, C 3 to C 6 alkenyl, —CH 2 CH 2 Z, —CH 2 COR 7 , —CH 2 CH═CHCOR 7
Y 1 and Y 3 are each, independently, N, or CH;
Y 2 and Y 4 are each independently, O, S, or NR 13 ;
R 7 is —OR 8 , —NHR 8 , —N(R 8 ) 2 , or —NHCH 2 CH 2 OR 8 ;
Z is —OR 8 , —OCH 2 CH 2 OR 8 , —N(R 8 ) 2 , or
R 8 is hydrogen, or C 1 to C 3 alkyl;
R 9 is C 1 to C 6 alkyl, C 3 to C 6 alkenyl, OH, NHR 10 , N(R 10 ) 2 , CH 2 COR 11 , —CH 2 CH═CHCOR 11 , or
R 10 is C 1 to C 3 alkyl, C 3 to C 4 alkenyl, phenyl, —CH 2 CH 2 OCH 3 , or
R 11 is —OR 12 , NHR 12 , —N(R 12 ) 2 , or —NHCH 2 CH 2 OR 12 ;
R 12 is hydrogen, or C 1 to C 3 alkyl;
R 13 is hydrogen, or C 1 to C 3 alkyl;
W is a bond, CH 2 , CH 2 CH 2 , O, S(O) q , NCHO, NCOCH 3 , or NR 12 ;
m is 0-2;
n is 0-2;
q is 0-2,
with the proviso that R 2 and R 3 are not both hydrogen;
or pharmaceutically acceptable salt thereof.
16 . A method of providing contraception in a male mammal in need thereof which comprises administering to said mammal a contraceptive effective amount of a compound of formula I having, the structure
wherein
Q is hydrogen or —SO 2 R 1 ;
X is a bond, O, S(O) n , —CH═CH—, —CH 2 CH 2 —, —C≡C—, or —CH 2 S(O) n CH 2 —;
R 1 is OH, NH 2 , C 1 to C 6 alkoxy, C 1 to C 3 perfluoroalkoxy;
Ar is
Ar′ is
R 2 and R 4 are each, independently, hydrogen, OR 6 , —S(O) m R 6 , —NHR 6 , —N(R 6 ) 2 , or —CH 2 SO 2 CH 3 ;
R 3 and R 5 are each, independently, hydrogen, —NO 2 , —NH 2 , —SO 2 R 9 , or —CH 2 R 9 ;
R 6 is hydrogen, C 1 to C 6 alkyl, C 3 to C 6 alkenyl, —CH 2 CH 2 Z, —CH 2 COR 7 , —CH 2 CH═CHCOR 7
Y 1 and Y 3 are each, independently, N, or CH;
Y 2 and Y 4 are each independently, O, S, or NR 13 ;
R 7 is —OR 8 , —NHR 8 , —N(R 8 ) 2 , or —NHCH 2 CH 2 OR 8 ;
Z is —OR 8 , —OCH 2 CH 2 OR 8 , —N(R 8 ) 2 , or
R 8 is hydrogen, or C 1 to C 3 alkyl;
R 9 is C 1 to C 6 alkyl, C 3 to C 6 alkenyl, OH, NHR 10 , N(R 10 ) 2 , CH 2 COR 11 , —CH 2 CH═CHCOR 11 , or
R 10 is C 1 to C 3 alkyl, C 3 to C 4 alkenyl, phenyl, —CH 2 CH 2 OCH 3 , or
R 11 is —OR 12 , NHR 12 , —N(R 12 ) 2 , or —NHCH 2 CH 2 OR 12 ;
R 12 is hydrogen, or C 1 to C 3 alkyl;
R 13 is hydrogen, or C 1 to C 3 alkyl;
W is a bond, CH 2 , CH 2 CH 2 , O, S(O) q , NCHO, NCOCH 3 , or NR 12 ;
m is 0-2;
n is 0-2;
q is 0-2,
with the proviso that R 2 and R 3 are not both hydrogen;
or pharmaceutically acceptable salt thereof.
17 . A pharmaceutical composition which comprises, a compound of formula I having the structure
wherein
Q is hydrogen or —SO 2 R 1 ;
X is a bond, O, S(O) n , —CH═CH—, —CH 2 CH 2 —, —C≡C—, or —CH 2 S(O) n CH 2 —;
R 1 is OH, NH 2 , C 1 to C 6 alkoxy, C 1 to C 3 perfluoroalkoxy;
R 2 and R 4 are each, independently, hydrogen, OR 6 , —S(O) m R 6 , —NHR 6 , —N(R 6 ) 2 , or —CH 2 SO 2 CH 3 ;
R 3 and R 5 are each, independently, hydrogen, —NO 2 , —NH 2 , —SO 2 R 9 , or —CH 2 R 9 ;
R 6 is hydrogen, C 1 to C 6 alkyl, C 3 to C 6 alkenyl, —CH 2 CH 2 Z, —CH 2 COR 7 , —CH 2 CH═CHCOR 7
Y 1 and Y 3 are each, independently, N, or CH;
Y 2 and Y 4 are each independently, O, S, or NR 13 ;
R 7 is —OR 8 , —NHR 8 , —N(R 8 ) 2 , or —NHCH 2 CH 2 OR 8 ;
Z is —OR 8 , —OCH 2 CH 2 OR 8 , —N(R 8 ) 2 , or
R 8 is hydrogen, or C 1 to C 3 alkyl;
R 9 is C 1 to C 6 alkyl, C 3 to C 6 alkenyl, OH, NHR 10 , N(R 10 ) 2 , CH 2 COR 11 , —CH 2 CH═CHCOR 11 , or
R 10 is C 1 to C 3 alkyl, C 3 to C 4 alkenyl, phenyl, —CH 2 CH 2 OCH 3 , or
R 11 is —OR 12 , —NHR 12 , —N(R 12 ) 2 , or —NHCH 2 CH 2 OR 12 ;
R 12 is hydrogen, or C 1 to C 3 alkyl;
R 13 is hydrogen, or C 1 to C 3 alkyl;
W is a bond, CH 2 , CH 2 CH 2 , O, S(O) q , NCHO, NCOCH 3 , or NR 12 ;
m is 0-2;
n is 0-2;
q is 0-2,
with the proviso that R 2 and R 3 are not both hydrogen;
or pharmaceutically acceptable salt thereof, and a pharmaceutical carrier.Cited by (0)
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