US5045565A — Novel compounds, pharmaceutical compositions, and…

Claim 1

Independent Claim 303 words

Beta-aminoethyl-substituted phenyl compounds which are effective as anti-inflammatory or analgesic agents, and the pharmaceutically-acceptable salts and amides thereof, having the general structure: ##STR45## wherein: (a) the --W--X-- moiety is selected from the group consisting of --C(O)NH--, --C(S)NH--, --S(O) 2 NH--, --NHC(O)O--, --NHC(S)O--, --NHC(O)NH-- and --NHC(S)NH-- wherein either available bond of the --W--X-- moiety is bonded to the --R moiety and the remaining bond is attached to the benzyl carbon atom; (b) --Y-- is a moiety selected from the group consisting of --O--, --S-- and --NR 4 --, where --R 4 is selected from hydrogen and C 1 -C 4 alkanyl; (c) --Z is selected from the group consisting of hydrogen, hydroxy, and methoxy; (d) --R is an alkyl group having from about 1 to about 24 carbon atoms; (e) --R 1 is selected from the group consisting of hydrogen, hydroxy, alkyl esters of hydroxy having from about 1 to about 5 carbon atoms, alkyl having from about 1 to about 5 carbon atoms, and alkoxy having from about 1 to about 5 carbon atoms; and (f) each --R 2 is independently selected from hydrogen, halogen, unsubstituted or substituted alkyl having from about 1 to about 6 carbon atoms, substituted or unsubstituted aryl, and carboxylate, or two --R 2 moieties are covalently bonded to form a substituted or unsubstituted alkyl or aryl ring having from about 3 to about 8 carbon atoms in the ring; wherein any alkyl ring substituent is selected from the group consisting of halogen, hydroxy, amino, aryl, carboxylate, and --OR 3 wherein --R 3 is unsubstituted alkyl having from about 1 to about 3 carbon atoms; and wherein any aryl substituent is selected from the group consisting of halogen, hydroxy, C 1 -C 16 alkoxy, amino, nitro, cyano, phenyl, benzyl, benzyloxy, trifluoromethyl, formylamino, carboxylate and C 1 -C 6 alkyl.

Claim 2

Dependent Claim 303 words

Beta-aminoethyl-substituted phenyl compounds which are effective as anti-inflammatory or analgesic agents, and the pharmaceutically-acceptable salts and amides thereof, having the general structure: ##STR45## wherein: (a) the --W--X-- moiety is selected from the group consisting of --C(O)NH--, --C(S)NH--, --S(O) 2 NH--, --NHC(O)O--, --NHC(S)O--, --NHC(O)NH-- and --NHC(S)NH-- wherein either available bond of the --W--X-- moiety is bonded to the --R moiety and the remaining bond is attached to the benzyl carbon atom; (b) --Y-- is a moiety selected from the group consisting of --O--, --S-- and --NR 4 --, where --R 4 is selected from hydrogen and C 1 -C 4 alkanyl; (c) --Z is selected from the group consisting of hydrogen, hydroxy, and methoxy; (d) --R is an alkyl group having from about 1 to about 24 carbon atoms; (e) --R 1 is selected from the group consisting of hydrogen, hydroxy, alkyl esters of hydroxy having from about 1 to about 5 carbon atoms, alkyl having from about 1 to about 5 carbon atoms, and alkoxy having from about 1 to about 5 carbon atoms; and (f) each --R 2 is independently selected from hydrogen, halogen, unsubstituted or substituted alkyl having from about 1 to about 6 carbon atoms, substituted or unsubstituted aryl, and carboxylate, or two --R 2 moieties are covalently bonded to form a substituted or unsubstituted alkyl or aryl ring having from about 3 to about 8 carbon atoms in the ring; wherein any alkyl ring substituent is selected from the group consisting of halogen, hydroxy, amino, aryl, carboxylate, and --OR 3 wherein --R 3 is unsubstituted alkyl having from about 1 to about 3 carbon atoms; and wherein any aryl substituent is selected from the group consisting of halogen, hydroxy, C 1 -C 16 alkoxy, amino, nitro, cyano, phenyl, benzyl, benzyloxy, trifluoromethyl, formylamino, carboxylate and C 1 -C 6 alkyl.

Claim 3

Dependent Claim 32 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 1, wherein --Y-- is --O--, and --R 1 is selected from the group consisting of hydrogen, hydroxy, and methyl.

Claim 4

Dependent Claim 87 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceuticlly-acceptable salts and amides thereof, according to claim 2, wherein --R 1 is hydrogen; both --R 2 on the alpha carbon atom are hydrogen; both --R 2 on the beta carbon atom are selected from hydrogen and alkyl having from 1 to about 5 carbon atoms or the --R 2 are covalently bonded to form an alkyl ring having from about 3 to about 6 carbon atoms, the alkyl or alkyl ring being unsubstituted or substituted with phenyl; and --Z is methoxy.

Claim 5

Dependent Claim 269 words

Beta-aminoethyl-substituted phenyl compounds which are effective as anti-inflammatory or analgesic agents, and the pharmaceutically-acceptable salts and amides thereof, having the general structure: ##STR46## wherein: (a) ═Q is selected from the group consisting of oxygen or sulfur; (b) --Y-- is a moiety selected from the group consisting of --O--, --S-- and --NR 4 --, where --R 4 is selected from hydrogen and C 1 -C 4 alkanyl; (c) --Z is selected from the group consisting of hydrogen, hydroxy, and methoxy; (d) --R is an alkyl group having from about 1 to about 24 carbon atoms; (e) --R 1 is selected from the group consisting of hydrogen, hydroxy, alkyl esters of hydroxy having from about 1 to about 5 carbon atoms, alkyl having from about 1 to about 5 carbon atoms, and alkoxy having from about 1 to about 5 carbon atoms; and (f) each --R 2 is independently selected from hydrogen, halogen, unsubstituted or substituted alkyl having from about 1 to about 6 carbon atoms, substituted or unsubstituted aryl, and carboxylate, or two --R 2 moieties are covalently bonded to form a substituted or unsubstituted alkyl or aryl ring having from about 3 to about 8 carbon atoms in the ring; wherein any alkyl ring substituent is selected from the group consisting of halogen, hydroxy, amino, aryl, carboxylate, and --OR 3 wherein --R 3 is unsubstituted alkyl having from about 1 to about 3 carbon atoms; and wherein any aryl substituent is selected from the group consisting of halogen, hydroxy, C 1 -C 16 alkoxy, amino, nitro, cyano, phenyl, benzyl, benzyloxy, trifluoromethyl, formylamino, carboxylate and C 1 -C 6 alkyl.

Claim 6

Dependent Claim 269 words

Beta-aminoethyl-substituted phenyl compounds which are effective as anti-inflammatory or analgesic agents, and the pharmaceutically-acceptable salts and amides thereof, having the general structure: ##STR46## wherein: (a) ═Q is selected from the group consisting of oxygen or sulfur; (b) --Y-- is a moiety selected from the group consisting of --O--, --S-- and --NR 4 --, where --R 4 is selected from hydrogen and C 1 -C 4 alkanyl; (c) --Z is selected from the group consisting of hydrogen, hydroxy, and methoxy; (d) --R is an alkyl group having from about 1 to about 24 carbon atoms; (e) --R 1 is selected from the group consisting of hydrogen, hydroxy, alkyl esters of hydroxy having from about 1 to about 5 carbon atoms, alkyl having from about 1 to about 5 carbon atoms, and alkoxy having from about 1 to about 5 carbon atoms; and (f) each --R 2 is independently selected from hydrogen, halogen, unsubstituted or substituted alkyl having from about 1 to about 6 carbon atoms, substituted or unsubstituted aryl, and carboxylate, or two --R 2 moieties are covalently bonded to form a substituted or unsubstituted alkyl or aryl ring having from about 3 to about 8 carbon atoms in the ring; wherein any alkyl ring substituent is selected from the group consisting of halogen, hydroxy, amino, aryl, carboxylate, and --OR 3 wherein --R 3 is unsubstituted alkyl having from about 1 to about 3 carbon atoms; and wherein any aryl substituent is selected from the group consisting of halogen, hydroxy, C 1 -C 16 alkoxy, amino, nitro, cyano, phenyl, benzyl, benzyloxy, trifluoromethyl, formylamino, carboxylate and C 1 -C 6 alkyl.

Claim 7

Dependent Claim 32 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 4, wherein --Y-- is --O--, and --R 1 is selected from the group consisting of hydrogen, hydroxy and methyl.

Claim 8

Dependent Claim 18 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 5, wherein ═Q is oxygen.

Claim 9

Dependent Claim 126 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 6, wherein --R 1 is hydrogen; both --R 2 on the alpha carbon atom are hydrogen; both --R 2 on the beta carbon atom are selected from hydrogen and alkyl having from 1 to about 5 carbon atoms or the --R 2 are covalently bonded to form an alkyl ring having from about 3 to about 6 carbon atoms, the alkyl or alkyl ring being unsubstituted or substituted with phenyl; and --R is selected from the group consisting of alkanyl groups having from about 6 to about 14 carbon atoms, alkenyl groups having from about 14 to about 22 carbon atoms, and alkynyl groups having from about 14 to about 22 carbon atoms.

Claim 10

Dependent Claim 55 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 7, wherein --Z is methoxy; and --R is selected from the group consisting of n-hexanyl, n-heptanyl, n-octanyl, n-nonanyl, n-decanyl, n-undecanyl, n-dodecanyl, n-tridecanyl, n-tetradecanyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, eicosenyl, docosenyl, octadecadienyl, nonadecadienyl, eicosadienyl, octadecatrienyl, eicosatrienyl, eicosatetraenyl, octadecynyl, nonadecynyl, eicosynyl, and docosynyl.

Claim 11

Dependent Claim 110 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 8, wherein both --R 2 on the beta carbon atom are selected from the group consisting of hydrogen, methyl, ethyl, and both --R 2 being covalently bonded to form a C 3 -C 5 saturated alkyl ring; and --R is selected from the group consisting of n-octanyl; n-nonanyl; n-decanyl; 9E- or 9Z-tetradecenyl; 9E- or 9Z-hexadecenyl; 9E- or 9Z-octadecenyl; 6E- or 6Z-octadecenyl; 11E- or 11Z-octadecenyl; 10E- or 10Z-nonadecenyl; 13E- or 13Z- docosenyl; 9-methylene-1-octadecanyl; 9Z,12Z-octadecadienyl; 9E, 12E-octadecadienyl; 9Z, 12E-octadecadienyl; 9Z, 11E-octadecadienyl; 10E, 13E-nonadecadienyl; 11E,14E-eicosadienyl; 9Z, 12Z, 15Z-octadecatrienyl; 6Z, 9Z, 12Z-octadecatrienyl; 11Z, 14Z, 17Z-eicosatrienyl; 5Z, 8Z, 11Z, 14Z-eicosatetraenyl; and 9-octadecynyl.

Claim 12

Dependent Claim 25 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 9, selected from the group consisting of N-(9Z-octadecenyl)-4-(2-aminoethoxy)-3-methoxyphenylacetamide, N-octanyl-4(2-aminoethoxy)-3-methoxyphenylacetamide, N-(9Z-octadecenyl)-4-(2-amino-2-methylpropoxy)-3-methoxyphenylacetamide, and N-octanyl-4-(2-amino-2-methylpropoxy)-3-methoxyphenylacetamide.

Claim 13

Dependent Claim 36 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 7, where both --R 2 on the alpha carbon atoms are hydrogen and both --R 2 on the beta carbon atom are methyl.

Claim 14

Dependent Claim 20 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 7, where all --R 2 are hydrogen.

Claim 15

Dependent Claim 269 words

Beta-aminoethyl-substituted phenyl compounds which are effective as anti-inflammatory or analgesic agents, and the pharmaceutically-acceptable salts and amides thereof, having the general structure: ##STR47## wherein: (a) ═Q is selected from the group consisting of oxygen or sulfur; (b) --Y-- is a moiety selected from the group consisting of --O--, --S-- and --NR 4 --, where --R 4 is selected from hydrogen and C 1 -C 4 alkanyl; (c) --Z is selected from the group consisting of hydrogen, hydroxy, and methoxy; (d) --R is an alkyl group having from about 1 to about 24 carbon atoms; (e) --R 1 is selected from the group consisting of hydrogen, hydroxy, alkyl esters of hydroxy having from about 1 to about 5 carbon atoms, alkyl having from about 1 to about 5 carbon atoms, and alkoxy having from about 1 to about 5 carbon atoms; and (f) each --R 2 is independently selected from hydrogen, halogen, unsubstituted or substituted alkyl having from about 1 to about 6 carbon atoms, substituted or unsubstituted aryl, and carboxylate, or two --R 2 moieties are covalently bonded to form a substituted or unsubstituted alkyl or aryl ring having from about 3 to about 8 carbon atoms in the ring; wherein any alkyl ring substituent is selected from the group consisting of halogen, hydroxy, amino, aryl, carboxylate, and --OR 3 wherein --R 3 is unsubstituted alkyl having from about 1 to about 3 carbon atoms; and wherein any aryl substituent is selected from the group consisting of halogen, hydroxy, C 1 -C 16 alkoxy, amino, nitro, cyano, phenyl, benzyl, benzyloxy, trifluoromethyl, formylamino, carboxylate and C 1 -C 6 alkyl.

Claim 16

Dependent Claim 269 words

Beta-aminoethyl-substituted phenyl compounds which are effective as anti-inflammatory or analgesic agents, and the pharmaceutically-acceptable salts and amides thereof, having the general structure: ##STR47## wherein: (a) ═Q is selected from the group consisting of oxygen or sulfur; (b) --Y-- is a moiety selected from the group consisting of --O--, --S-- and --NR 4 --, where --R 4 is selected from hydrogen and C 1 -C 4 alkanyl; (c) --Z is selected from the group consisting of hydrogen, hydroxy, and methoxy; (d) --R is an alkyl group having from about 1 to about 24 carbon atoms; (e) --R 1 is selected from the group consisting of hydrogen, hydroxy, alkyl esters of hydroxy having from about 1 to about 5 carbon atoms, alkyl having from about 1 to about 5 carbon atoms, and alkoxy having from about 1 to about 5 carbon atoms; and (f) each --R 2 is independently selected from hydrogen, halogen, unsubstituted or substituted alkyl having from about 1 to about 6 carbon atoms, substituted or unsubstituted aryl, and carboxylate, or two --R 2 moieties are covalently bonded to form a substituted or unsubstituted alkyl or aryl ring having from about 3 to about 8 carbon atoms in the ring; wherein any alkyl ring substituent is selected from the group consisting of halogen, hydroxy, amino, aryl, carboxylate, and --OR 3 wherein --R 3 is unsubstituted alkyl having from about 1 to about 3 carbon atoms; and wherein any aryl substituent is selected from the group consisting of halogen, hydroxy, C 1 -C 16 alkoxy, amino, nitro, cyano, phenyl, benzyl, benzyloxy, trifluoromethyl, formylamino, carboxylate and C 1 -C 6 alkyl.

Claim 17

Dependent Claim 32 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 13, wherein --Y-- is --O--, and --R 1 is selected from the group consisting of hydrogen, hydroxy and methyl.

Claim 18

Dependent Claim 18 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 14, wherein ═Q is oxygen.

Claim 19

Dependent Claim 126 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 15, wherein --R 1 is hydrogen; both --R 2 on the alpha carbon atom are hydrogen; both --R 2 on the beta carbon atom are selected from hydrogen and alkyl having from 1 to about 5 carbon atoms or the --R 2 are covalently bonded to form an alkyl ring having from about 3 to about 6 carbon atoms, the alkyl or alkyl ring being unsubstituted or substituted with phenyl; and --R is selected from the group consisting of alkanyl groups having from about 6 to about 14 carbon atoms, alkenyl groups having from about 14 to about 22 carbon atoms, and alkynyl groups having from about 14 to about 22 carbon atoms.

Claim 20

Dependent Claim 58 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 16, wherein --Z is methoxy; and --R is selected from the group consisting of n-hexanyl, n-heptanyl, n-octanyl, n-nonanyl, n-decanyl, n-undecanyl, n-dodecanyl, n-tridecanyl, tridecenyl, tetradecenyl, pentadecenyl, hexadecenyl, heptadecenyl, octadecenyl, nonadecenyl, eicosenyl, docosenyl, heptadecadienyl, octadecadienyl, nonadecadienyl, eicosadienyl, heptadecatrienyl, octadecatrienyl, nonadecatrienyl, eicosatrienyl, nonadecatetraenyl, heptadecynyl, octadecynyl, nonadecynyl, and eicosynyl.

Claim 21

Dependent Claim 27 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 17, selected from the group consisting of N-((4-(2-aminoethoxy)-3-methoxyphenyl)-methyl)-9Z-octadecenamide; N-((4-(2-aminoethoxy)-3-methoxyphenyl)-methyl)-nonanamide; N-((4-(2-methyl-2-aminopropoxy)-3-methoxyphenyl)-methyl)-9Z-octadecenamide; N-((4-(2(S)-amino-3-methylbutoxy)-3-methoxyphenyl)-methyl)-9Z-octadecenamide; N-((4-(2-amino-3-hydroxypropoxy)-3-methoxyphenyl)-methyl)-9Z-octadecenamide; and N-((4-(2-amino-2-carboxyethoxy)-3-methoxyphenyl)-methyl)-9Z-octadecenamide

Claim 22

Dependent Claim 110 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 17, wherein both --R 2 on the beta carbon atom are selected from the group consisting of hydrogen, methyl, ethyl, and both --R 2 being covalently bonded to form a C 3 -C 5 saturated alkyl ring; and --R is selected from the group consisting of n-heptanyl; n-octanyl; n-nonanyl; 8E- or 8Z-tridecenyl; BE- or 8Z-pentadecenyl; 8E- or 8Z-heptadecenyl; 5E- or 5Z-heptadecenyl; 10E- or 10Z-heptadecenyl; 9E- or 9Z-octadecenyl; 12E- or 12Z-nonadecenyl; 8-methylene-1-heptadecanyl; 8Z, 11Z-heptadecadienyl; 8E, 11E-heptadecadienyl; 8Z, 11E-heptadecadienyl; 8Z, 10E-heptadecadienyl; 9E, 12E-octadecadienyl; 10E,13E-nonadecadienyl; 8Z, 11Z, 14Z-heptadecatrienyl; 5Z, 8Z, 11Z-heptadecatrienyl; 10Z, 13Z, 16Z-nonadecatrienyl; 4Z, 7Z, 10Z, 13Z-nonadecatetraenyl; and 8-heptadecynyl.

Claim 23

Dependent Claim 25 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 19, selected from the group consisting of N-((4-(2-aminoethoxy)-3-methoxyphenyl)-methyl)-9Z-octadecenamide, N-((4(2-aminoethoxy)-3-methoxyphenyl)-methyl)-nonanamide, N-((4-(2-methyl-2-aminopropoxy)-3-methoxyphenyl)-methyl)-9Z-octadecenamide, and N-((4-(2-methyl-2-aminopropoxy)-3-methoxyphenyl)-methyl)nonanamide.

Claim 24

Dependent Claim 36 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 16, wherein both --R 2 on the alpha carbon atoms are hydrogen and both --R 2 on the beta carbon atom are methyl.

Claim 25

Dependent Claim 20 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 16, where all --R 2 are hydrogen.

Claim 26

Dependent Claim 19 words

Beta-aminoethyl-substituted phenyl compounds, and the pharmaceutically-acceptable salts and amides thereof, according to claim 19, wherein the compound is N-((4-(2-aminoethoxy)-3-methoxyphenyl)-methyl)-9Z-octadecenamide.

Claim 27

Dependent Claim 31 words

Pharmaceutical compositions comprising: (a) a safe and effective amount of a compound according to any of claim 1, 3, 4, 7, 9, 13, 16, or 19; and (b) a pharmaceutically-acceptable carrier.

Annuity Stage	Window Opens	Payment Deadline	Surcharge Period Until	Estimated Fee	Status
3.5 Years (Year 4)	1994-09-02	1995-03-04	1995-09-03	$2000.00	Window Closed / Lapsed
7.5 Years (Year 8)	1998-09-02	1999-03-04	1999-09-03	$3760.00	Window Closed / Lapsed
11.5 Years (Year 12)	2002-09-02	2003-03-04	2003-09-03	$7700.00	Window Closed / Lapsed

Novel compounds, pharmaceutical compositions, and methods for treating inflammation and pain

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