Protein kinase C modulators

Claim 2

A protein kinase C modulator compound represented by the formula: ##STR5## in which: X and Y independently are, C 10-20 alkyl, C(O)E, C(O)C 10 -C 20 alkyl, C(O)C 10 -C 20 alkenyl or S(O 2 )C 10 -C 20 alkyl with the proviso that they are not the same; E is CH(NH 2 )FG or CH 2 FG; F is C 1-10 alkylene; G is NH 2 , cyclo C 3-8 alkyl, CO 2 H, phenyl, guanidino, C(O)NH 2 , OH, SH, SC 1-5 alkyl, or CO 2 M; M is C1-8 alkyl, phenyl, phenyl substituted by one or more C 1-4 alkyl, halogen, hydroxy, C 1-4 alkoxy, or amino, benzyl or benzyl substituted by one or more C 1-4 alkyl, halogen, hydroxy, C 1-4 alkoxy, or amino; and Z is hydrogen or C 1 -C 5 alkyl; or any pharmaceutically acceptable salt or hydrate thereof.

Claim 3

A compound of claim 1 wherein Y is C(O)E and E is CH(NH 2 )FG.

Claim 4

A compound of claim 3 wherein X is C 10-20 alkyl.

Claim 5

A compound of claim 3 that is 2,6-diamino-N-[(1-(1-oxotridecy)-2-piperidinyl)methyl]hexanamide, 2,5-diamino-N-[(1-(oxotridecyl)-2-piperidinyl)methyl]pentanamide, or pharmaceutically acceptable salts or hydrates thereof.

Claim 6

A compound of claim 1 that is: 3-amino-4-oxo-4-[([1-(1-oxotridecyl)-2-piperidinyl]methyl)amino]butanoic acid phenylmethyl ester, 2-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)ethanamide, 2-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)propanamide, 3-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)propanamide, 4-amino-5-oxo-5-[([1-(1-oxotridecyl)-2-piperidinyl]methyl)amino]pentanamide 2-amino-3-hydroxy-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)propanamide, N-[([1-oxotridecyl)-2-piperidinyl]methyl)amino]3-methyloxopiperidine, 2-amino-3-phenyl-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)propanamide, 2-amino-5-guanidyl-N-([1-(oxotridecyl]-2-piperidinyl]methyl)pentamide, 2,6-diamino-N-([1-(1-oxoundecyl)-2-piperidinyl]-methyl)hexanamide, 2,6-diamino-N-([1-(1-oxododecyl)-2-piperidinyl]-methyl)hexanamide, 2,6-diamino-N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxopentadecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxohexadecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxoheptadecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxooctadecyl)-2-piperidinyl]methyl)hexanamide, N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)amine, 2-amino-4-methyl-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)pentanamide 2-amino-4-methylthio-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)butanamide, 2-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)-2-phenylpropanamide, 6-amino-N-([1-(1-oxotetradecyl)-2-piperidinyl]-methyl)hexanamide, 2-amino-5-guanidyl-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)pentanamide, 2,6-diamino-N-([1-(dodecylsulfonyl)-2-piperidinyl]methyl)hexanamide, 2,3-diamino-N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)propanamide, 2,6-diamino-N-([E-1-oxoocta-9-decenyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([Z-1-oxoocta-9-decenyl)-2-piperidinyl]methyl)hexanamide, (2R)-2,6-diamino-N-{(2R)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2R)-2,6-diamino-N-{(2S)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2S)-2,6-diamino-N-{(2R)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2S)-2,6-diamino-N-{(2S)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide, or pharmaceutically acceptable salts or hydrates thereof.

Claim 7

A pharmaceutical composition useful for inhibiting PKC activity in mammals comprising a pharmaceutical carrier and a PKC inhibiting compound of claim 1.

Claim 8

A pharmaceutical composition of claim 6 wherein the compound is 2,6-diamino-N-[(1-(1-oxotridecyl)-2-piperidinyl)methyl]hexanamide, 2,5-diamino-N-[(1-(oxotridecyl)-2-piperidinyl)methyl]pentanamide, or pharmaceutically acceptable salts or hydrates thereof.

Claim 9

A pharmaceutical composition of claim 6 wherein the compound is 3-amino-4-oxo-4-[([1-(1-oxotridecyl)-2-piperidinyl]methyl)amino]butanoic acid phenylmethyl ester, 2-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)-ethanamide, 2-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)-propanamide, 3-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)-propanamide, 4-amino-5-oxo-5-[([1-(1-oxotridecyl)-2-piperidinyl]-methyl)amino]pentanamide, 2-amino-3-hydroxy-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)propanamide, N-[([1-oxotridecyl)-2-piperidinyl]methyl)amino]3-methyloxopiperidine, 2-amino-3-phenyl-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)propanamide, 2-amino-5-guanidyl-N-([1-(oxotridecyl]-2-piperidinyl]methyl)pentamide, 2,6-diamino-N-([1-(1-oxoundecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxododecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxopentadecyl)-2piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxohexadecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxoheptadecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxooctadecyl)-2-piperidinyl]methyl)hexanamide, N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)amine, 2-amino-4-methyl-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)pentanamide 2-amino-4-methylthio-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)butanamide, 2-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)-2-phenylpropanamide, 6-amino-N-([1-(1-oxotetradecyl)-2-piperidinyl]-methyl)hexanamide, 2-amino-5-guanidyl-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)pentanamide,

Claim 10

6-diamino-N-([1-(dodecylsulfonyl)-2-piperidinyl]methyl)hexanamide, 2,3-diamino-N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)propanamide, 2,6-diamino-N-([E-1-oxoocta-9-decenyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([Z-1-oxoocta-9-decenyl)-2-piperidinyl]methyl)hexanamide, (2R)-2,6-diamino-N-{(2R)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2R)-2,6-diamino-N-{(2S)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2S)-2,6-diamino-N-{(2R)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2S)-2,6-diamino-N-{(2S)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide, or pharmaceutically acceptable salts or hydrates thereof.

Claim 11

6-diamino-N-([1-(dodecylsulfonyl)-2-piperidinyl]methyl)hexanamide, 2,3-diamino-N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)propanamide, 2,6-diamino-N-([E-1-oxoocta-9-decenyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([Z-1-oxoocta-9-decenyl)-2-piperidinyl]methyl)hexanamide, (2R)-2,6-diamino-N-{(2R)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2R)-2,6-diamino-N-{(2S)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2S)-2,6-diamino-N-{(2R)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2S)-2,6-diamino-N-{(2S)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide, or pharmaceutically acceptable salts or hydrates thereof.

Claim 12

A method for inhibiting PCK activity in mammals that comprises administering to a subject an amount of a PKC inhibiting compound of claim 1 effective to produce anti-inflammatory, anti-convulsant, or cerebral protective activity.

Claim 13

A method of claim 9 wherein the compound is 2,6-diamino-N-[(1-(1-oxotridecyl)-2-piperidinyl)methyl]hexanamide, 2,5-diamino-N-[(1-(oxotridecyl)-2-piperidinyl)methyl)pentanamide, or pharmaceutically acceptable salts or hydrates thereof.

Claim 14

A method of claim 9 wherein the compound is 3-amino-4-oxo-4-[([1-(1-oxotridecyl)-2-piperidinyl]methyl)amino]butanoic acid phenylmethyl ester, 2-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)ethanamide, 2-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)propanamide, 3-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)propanamide, 4-amino-5-oxo-5-[([1-(1-oxotridecyl)-2-piperidinyl]methyl)amino]pentanamide 2-amino-3-hydroxy-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)propanamide, N-[([1-oxotridecyl)-2-piperidinyl]methyl)amino]3-methyloxopiperidine, 2-amino-3-phenyl-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)propanamide, 2-amino-5-guanidyl-N-([1-(oxotridecyl]-2-piperidinyl]methyl)pentamide, 2,6-diamino-N-([1-(1-oxoundecyl)-2-piperidinyl]-methyl)hexanamide, 2,6-diamino-N-([1-(1-oxododecyl)-2-piperidinyl]-methyl)hexanamide,

Claim 15

6-diamino-N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxopentadecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxohexadecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxoheptadecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxooctadecyl)-2-piperidinyl]methyl)hexanamide, N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)amine, 2-amino-4-methyl-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)pentanamide 2-amino-4-methylthio-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)butanamide, 2-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)-2-phenylpropanamide, 6-amino-N-([1-(1-oxotetradecyl)-2-piperidinyl]-methyl)hexanamide, 2-amino-5-guanidyl-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)pentanamide, 2,6-diamino-N-([1-(dodecylsulfonyl)-2-piperidinyl]methyl)hexanamide, 2,3-diamino-N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)propanamide, 2,6-diamino-N-([E-1-oxoocta-9-decenyl)-2-piperidinyl]methyl)hexanamide,

Claim 16

6-diamino-N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxopentadecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxohexadecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxoheptadecyl)-2-piperidinyl]methyl)hexanamide, 2,6-diamino-N-([1-(1-oxooctadecyl)-2-piperidinyl]methyl)hexanamide, N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)amine, 2-amino-4-methyl-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)pentanamide 2-amino-4-methylthio-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)butanamide, 2-amino-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)-2-phenylpropanamide, 6-amino-N-([1-(1-oxotetradecyl)-2-piperidinyl]-methyl)hexanamide, 2-amino-5-guanidyl-N-([1-(1-oxotridecyl)-2-piperidinyl]methyl)pentanamide, 2,6-diamino-N-([1-(dodecylsulfonyl)-2-piperidinyl]methyl)hexanamide, 2,3-diamino-N-([1-(1-oxotetradecyl)-2-piperidinyl]methyl)propanamide, 2,6-diamino-N-([E-1-oxoocta-9-decenyl)-2-piperidinyl]methyl)hexanamide,

Claim 17

6-diamino-N-([Z-1-oxoocta-9-decenyl)-2-piperidinyl]methyl)hexanamide, (2R)-2,6-diamino-N-{(2R)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2R)-2,6-diamino-N-{(2S)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2S)-2,6-diamino-N-{(2R)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2S)-2,6-diamino-N-{(2S)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide, or pharmaceutically acceptable salts or hydrates thereof.

Claim 18

6-diamino-N-([Z-1-oxoocta-9-decenyl)-2-piperidinyl]methyl)hexanamide, (2R)-2,6-diamino-N-{(2R)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2R)-2,6-diamino-N-{(2S)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2S)-2,6-diamino-N-{(2R)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide (2S)-2,6-diamino-N-{(2S)-[1-(1-oxotridecyl)-2-piperidinyl]methyl}hexanamide, or pharmaceutically acceptable salts or hydrates thereof.