US5382598A — Therapeutic amides

Claim 1

Independent Claim 268 words

An amide of the following formula I, wherein: E is CZ wherein C is a ring carbon and Z is a substituent defined below, wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of: phenyl substituted with 0-2 substituents selected from halo, hydroxy, cyano, (1-4C)alkyl, and (1-4C)alkoxy, provided that the 4-position of said phenyl may be substituted by fluoro only, and that the said phenyl may not be 3,5-disubstituted; provided that Ar is not 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl or 3-(1-4C)alkylphenyl when Y is carbonyl; and Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; (B) X is cyano and Z is selected from the group consisting of phenylthio, phenylsulfinyl, and phenylsulfonyl the phenyl rings of which are substituted with 0-2 substituents selected from halo, hydroxy, cyano, nitro (1-4C)alkyl, and (1-4)alkoxy; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring; and pharmaceutically acceptable in vivo hydrolyzable esters of said amide; and pharmaceutically acceptable salts of said amide and said esters.

Claim 2

Dependent Claim 268 words

An amide of the following formula I, wherein: E is CZ wherein C is a ring carbon and Z is a substituent defined below, wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of: phenyl substituted with 0-2 substituents selected from halo, hydroxy, cyano, (1-4C)alkyl, and (1-4C)alkoxy, provided that the 4-position of said phenyl may be substituted by fluoro only, and that the said phenyl may not be 3,5-disubstituted; provided that Ar is not 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl or 3-(1-4C)alkylphenyl when Y is carbonyl; and Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; (B) X is cyano and Z is selected from the group consisting of phenylthio, phenylsulfinyl, and phenylsulfonyl the phenyl rings of which are substituted with 0-2 substituents selected from halo, hydroxy, cyano, nitro (1-4C)alkyl, and (1-4)alkoxy; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring; and pharmaceutically acceptable in vivo hydrolyzable esters of said amide; and pharmaceutically acceptable salts of said amide and said esters.

Claim 3

Dependent Claim 178 words

An amide as claimed in claim 1 which is of the following formula Id, ##STR3## wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of phenyl, 2-, 3- and 4-fluorophenyl, 2- and 3-chlorophenyl, 2- and 3-cyanophenyl, 2- and 3-hydroxyphenyl, 2- and 3-methoxyphenyl, and 2- and 3-methylphenyl[, 2-, 3-, and 4-pyridyl, 2- and 4-pyrimidinyl, 3- and 4-isothiazolyl, 2- and 4-oxazolyl, 2- and 4-thiazolyl, 2- and 3-furyl, and 2- and 3-thienyl]; Z is selected from hydrogen, cyano, halo, hydroxy, (1-2C)alkyl, and (1-2C)alkoxy; (B) X is CN, Z is phenylsulfonyl; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 fluoro groups wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; and pharmaceutically acceptable in vivo hydrolyzable esters of said amide; and pharmaceutically acceptable salts of said amides and said esters.

Claim 4

Dependent Claim 164 words

An amide as claimed in claim 2, wherein X is ArY and wherein Ar, Y, and Z are selected from the group consisting of: (i) Y is sulfonyl, Z is hydrogen, and Ar is selected from the group consisting of: phenyl substituted with 0-1 substitutents, selected from phenyl, 2-, 3-, and 4-fluorophenyl, 2- and 3-chlorophenyl, 2- and 3-methoxyphenyl, 2- and 3-cyanophenyl, 2- and 3-hydroxyphenyl, and 2- and 3-methylphenyl; (ii) Y is sulfonyl, Ar is phenyl and Z is selected from the group consisting of cyano, fluoro, hydroxy, methoxy and methyl; and (iii) Y is carbonyl, Z is hydrogen, and Ar is phenyl; and R 2 and R 3 are independently selected from the group consisting of (i) R 2 is trifluoromethyl and R 3 is selected from methyl, ethyl, and trifluoromethyl; and (ii) R 2 is difluoromethyl and R 3 is difluoromethyl; and the pharmaceutically acceptable in vivo hydrolyzable esters of said amide, and pharmaceutically acceptable salts of said amide and said hydrolyzable esters.

Claim 5

Dependent Claim 35 words

An amide as claimed in claim 3, which is selected from: N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; S-(-)-N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; and N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethylmethylpropanamide; and pharmaceutically acceptable in vivo hydrolyzable esters of said amide; and pharmaceutically acceptable salts of said amide and said esters.

Claim 6

Dependent Claim 283 words

A pharmaceutical composition comprising an amide of the following formula I, or a pharmaceutically acceptable in vivo hydrolyzable ester of said amide, or a pharmaceutically acceptable salt of said amide or of said ester, ##STR4## wherein: E is CZ wherein C is a ring carbon and Z is a substituent defined below, wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of: phenyl substituted with 0-2 substituents selected from halo, hydroxy, cyano, (1-4C)alkyl, and (1-4C)alkoxy, provided that the 4-position of said phenyl may be substituted by fluoro only, and that the said phenyl may not be 3,5-disubstituted; provided that Ar is not 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl or 3-(1-4C) alkylphenyl when Y is carbonyl; and Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; (B) X is cyano and Z is selected from the group consisting of phenylthio, phenylsulfinyl, and phenylsulfonyl the phenyl rings of which are substituted with 0-2 substituents selected from halo, hydroxy, cyano, nitro (1-4C)alkyl, and (1-4)alkoxy; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring; and pharmaceutically acceptable diluent or carrier.

Claim 7

Dependent Claim 283 words

A pharmaceutical composition comprising an amide of the following formula I, or a pharmaceutically acceptable in vivo hydrolyzable ester of said amide, or a pharmaceutically acceptable salt of said amide or of said ester, ##STR4## wherein: E is CZ wherein C is a ring carbon and Z is a substituent defined below, wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of: phenyl substituted with 0-2 substituents selected from halo, hydroxy, cyano, (1-4C)alkyl, and (1-4C)alkoxy, provided that the 4-position of said phenyl may be substituted by fluoro only, and that the said phenyl may not be 3,5-disubstituted; provided that Ar is not 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl or 3-(1-4C) alkylphenyl when Y is carbonyl; and Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; (B) X is cyano and Z is selected from the group consisting of phenylthio, phenylsulfinyl, and phenylsulfonyl the phenyl rings of which are substituted with 0-2 substituents selected from halo, hydroxy, cyano, nitro (1-4C)alkyl, and (1-4)alkoxy; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring; and pharmaceutically acceptable diluent or carrier.

Claim 8

Dependent Claim 139 words

A composition as claimed in claim 5, wherein said amide is of the following formula Id, ##STR5## wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of phenyl, 2-, 3- and 4-fluorophenyl, 2- and 3-chlorophenyl, 2- and 3-¢cyanophenyl, 2- and 3-hydroxyphenyl, 2- and 3-methoxyphenyl, and 2- and 3-methylphenyl; Z is selected from hydrogen, cyano, halo, hydroxy, (1-2C) alkyl, and (1-2C) alkoxy; (B) X is CN, Z is phenylsulfonyl; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 fluoro groups wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl.

Claim 9

Dependent Claim 152 words

A composition as claimed in claim 6, wherein X is ArY and wherein Ar, Y, and Z are selected from the group consisting of: (i) Y is sulfonyl, Z is hydrogen, and Ar is selected from the group consisting of: phenyl substituted with 0-1 substitutents, selected from phenyl, 2-, 3-, and 4-fluorophenyl, 2- and 3-chlorophenyl, 2- and 3-methoxyphenyl, 2- and 3-cyanophenyl, 2- and 3-hydroxyphenyl, and 2- and 3-methylphenyl; (ii) Y is sulfonyl, Ar is phenyl and Z is selected from the group consisting of cyano, fluoro, hydroxy, methoxy and methyl; and (iii) Y is carbonyl, Z is hydrogen, and Ar is; and R 2 and R 3 are independently selected from the group consisting of (i) R 2 is trifluoromethyl and R 3 is selected from methyl, ethyl, and trifluoromethyl; and (ii) R 2 is difluoromethyl and R 3 is difluoromethyl; and the pharmaceutically acceptable in vivo hydrolyzable esters of said amide.

Claim 10

Dependent Claim 17 words

A composition as claimed in claim 7, wherein said amide is selected from: N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; S-(-)-N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; and N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethylmethylpropanamide.

Claim 11

Independent Claim 294 words

A method of treating urinary incontinence, comprising administering to a mammal in need of such treatment an effective amount of an amide of the following formula I, or a pharmaceutically acceptable in vivo hydrolyzable ester of said amide, or a pharmaceutically acceptable salt of said amide or of said ester, ##STR6## wherein: E is CZ wherein C is a ring carbon and Z is a substituent defined below, wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of: phenyl substituted with 0-2 substituents selected from halo, hydroxy, cyano, (1-4C)alkyl, and (1-4C)alkoxy, provided that the 4-position of said phenyl may be substituted by fluoro only, and that the said phenyl may not be 3,5-disubstituted; provided that Ar is not 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl or 3-(1-4C) alkylphenyl when Y is carbonyl; and Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C) alkyl, and (1-4C)alkoxy; (B) X is cyano and Z is selected from the group consisting of phenylthio, phenylsulfinyl, and phenylsulfonyl the phenyl rings of which are substituted with 0-2 substituents selected from halo, hydroxy, cyano, nitro (1-4C)alkyl, and (1-4)alkoxy; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring.

Claim 12

Independent Claim 294 words

A method of treating urinary incontinence, comprising administering to a mammal in need of such treatment an effective amount of an amide of the following formula I, or a pharmaceutically acceptable in vivo hydrolyzable ester of said amide, or a pharmaceutically acceptable salt of said amide or of said ester, ##STR6## wherein: E is CZ wherein C is a ring carbon and Z is a substituent defined below, wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of: phenyl substituted with 0-2 substituents selected from halo, hydroxy, cyano, (1-4C)alkyl, and (1-4C)alkoxy, provided that the 4-position of said phenyl may be substituted by fluoro only, and that the said phenyl may not be 3,5-disubstituted; provided that Ar is not 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl or 3-(1-4C) alkylphenyl when Y is carbonyl; and Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C) alkyl, and (1-4C)alkoxy; (B) X is cyano and Z is selected from the group consisting of phenylthio, phenylsulfinyl, and phenylsulfonyl the phenyl rings of which are substituted with 0-2 substituents selected from halo, hydroxy, cyano, nitro (1-4C)alkyl, and (1-4)alkoxy; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring.

Claim 13

Dependent Claim 137 words

A method as claimed in claim 9 wherein said amide is of the following formula Id, ##STR7## wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of phenyl, 2-, 3- and 4-fluorophenyl, 2- and 3-chlorophenyl, 2- and 3-cyanophenyl, 2- and 3-hydroxyphenyl, 2- and 3-methoxyphenyl, and 2- and 3-methylphenyl; Z is selected from hydrogen, cyano, halo, hydroxy, (1-2C)alkyl, and (1-2C)alkoxy; (B) X is CN, Z is phenylsulfonyl; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 fluoro groups wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl.

Claim 14

Dependent Claim 141 words

A method as claimed in claim 10, wherein X is ArY and wherein Ar, Y, and Z are selected from the group consisting of: (i) Y is sulfonyl, Z is hydrogen, and Ar is selected from the group consisting of: phenyl substituted with 0-1 substitutents, selected from phenyl, 2-, 3-, and 4-fluorophenyl, 2- and 3-chlorophenyl, 2- and 3-methoxyphenyl, 2- and 3-cyanophenyl, 2- and 3-hydroxyphenyl, and 2- and 3-methylphenyl; (ii) Y is sulfonyl, Ar is phenyl and Z is selected from the group consisting of cyano, fluoro, hydroxy, methoxy and methyl; and (iii) Y is carbonyl, Z is hydrogen, and Ar is; and R 2 and R 3 are independently selected from the group consisting of (i) R 2 is trifluoromethyl and R 3 is selected from methyl, ethyl, and trifluoromethyl; and (ii) R 2 is difluoromethyl and R 3 is difluoromethyl.

Claim 15

Dependent Claim 16 words

A method as claimed in claim 11, wherein said amide is selected from: N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; S-(-)-N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethylmethylpropanamide.

Claim 16

Dependent Claim 250 words

An amide of the following formula I, ##STR8## wherein: E is CZ wherein C is a ring carbon and Z is a substituent defined below, wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of: phenyl substituted with 0-2 substituents selected from halo, hydroxy, cyano, (1-4C)alkyl, and (1-4C)alkoxy, provided that the 4-position of said phenyl may be substituted by fluoro only, and that the said phenyl may not be 3,5-disubstituted; provided that Ar is not 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl or 3-(1-4C) alkylphenyl when Y is carbonyl; and Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; (B) X is cyano and Z is selected from the group consisting of phenylthio, phenylsulfinyl, and phenylsulfonyl the phenyl rings of which are substituted with 0-2 substituents selected from halo, hydroxy, cyano, nitro (1-4C)alkyl, and (1-4)alkoxy; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring.

Claim 17

Dependent Claim 250 words

An amide of the following formula I, ##STR8## wherein: E is CZ wherein C is a ring carbon and Z is a substituent defined below, wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of: phenyl substituted with 0-2 substituents selected from halo, hydroxy, cyano, (1-4C)alkyl, and (1-4C)alkoxy, provided that the 4-position of said phenyl may be substituted by fluoro only, and that the said phenyl may not be 3,5-disubstituted; provided that Ar is not 3-chlorophenyl, 3-bromophenyl, 3-iodophenyl or 3-(1-4C) alkylphenyl when Y is carbonyl; and Z is selected from hydrogen, cyano, halo, hydroxy, (1-4C)alkyl, and (1-4C)alkoxy; (B) X is cyano and Z is selected from the group consisting of phenylthio, phenylsulfinyl, and phenylsulfonyl the phenyl rings of which are substituted with 0-2 substituents selected from halo, hydroxy, cyano, nitro (1-4C)alkyl, and (1-4)alkoxy; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 groups selected from fluoro and chloro wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl; or together, with the carbon atom to which both R 2 and R 3 are attached, form a 3-5 membered cycloalkyl ring optionally substituted by from 0 to 2m-2 fluoro groups wherein m is the number of carbon atoms in said ring.

Claim 18

Dependent Claim 135 words

An amide as claimed in claim 13 which is of the following formula Id, ##STR9## wherein: X and Z are selected from the group consisting of: (A) X is ArY wherein Y is a linking group selected from carbonyl, sulfinyl, and sulfonyl and Ar is selected from the group consisting of phenyl, 2-, 3- and 4-fluorophenyl, 2- and 3-chlorophenyl, 2- and 3-cyanophenyl, 2- and 3-hydroxyphenyl, 2- and 3-methoxyphenyl, and 2- and 3-methylphenyl; Z is selected from hydrogen, cyano, halo, hydroxy, (1-2C)alkyl, and (1-2C)alkoxy; (B) X is CN, Z is phenylsulfonyl; R 2 and R 3 are independently selected from the group consisting of (1-3C)alkyl substituted by from 0 to 2k+1 fluoro groups wherein k is the number of carbon atoms in the said (1-3C)alkyl, provided that R 2 and R 3 are not both methyl.

Claim 19

Dependent Claim 143 words

An amide as claimed in claim 14, wherein X is ArY and wherein Ar, Y, and Z are selected from the group consisting of: (i) Y is sulfonyl, Z is hydrogen, and Ar is selected from the group consisting of: phenyl substituted with 0-1 substitutent, selected from phenyl, 2-, 3-, and 4-fluorophenyl, 2- and 3-chlorophenyl, 2- and 3-methoxyphenyl, 2- and 3-cyanophenyl, 2- and 3-hydroxyphenyl, and 2- and 3-methylphenyl; (ii) Y is sulfonyl, Ar is phenyl, and Z is selected from the group consisting of cyano, fluoro, hydroxy, methoxy and methyl; and (iii) Y is carbonyl, Z is hydrogen, and Ar is phenyl and; and R 2 and R 3 are independently selected from the group consisting of (i) R 2 is trifluoromethyl and R 3 is selected from methyl, ethyl, and trifluoromethyl; and (ii) R 2 is difluoromethyl and R 3 is difluoromethyl.

Claim 20

Dependent Claim 15 words

An amide as claimed in claim 15, which is selected from: N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; S-(-)-N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide; and N-[4-(Phenylcarbonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-trifluoromethylmethylpropanamide.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1998-01-16	1998-07-18	1999-01-17	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	2002-01-16	2002-07-18	2003-01-17	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2006-01-16	2006-07-18	2007-01-17	$7700.00	Window Closed / Lapsed

Therapeutic amides

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