Granted Patent B2

US 7,323,496 · App. 10/430,677 · Granted Jan 29, 2008

Assignee: Theracos, Inc.

Abstract

Claims (32)

1. A compound, or salt, hydrate or solvate thereof, represented by at least one of the following Formulas I, III, VI, VII, IX and XIII:

wherein the stereocenters marked with an asterisk (*) are R— or S—; the bond represented by a dashed line plus a solid line is a double bond or a single bond; and wherein

R 1 , R 2 , R 3 , R 4 , R 5 , R 6 and R 7 independently represent a hydrogen atom, or an optionally substituted C 1 -C 20 linear or branched alkyl, chloroalkyl or fluoroalkyl; optionally substituted C 2 -C 20 linear or branched alkenyl; optionally substituted C 6 -C 20 aryl, linear or branched alkylaryl, linear or branched alkenylaryl; COOR where R independently represents a hydrogen atom, or an optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl, or a pharmaceutically acceptable counter-ion; CONR′R″, where R′ and R″ independently represent a hydrogen atom, or an optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl; optionally substituted C 1 -C 6 amidoalkyl; NH 2 ; C 1 -C 20 alkylamino, bis(alkylamino) or cycloalkylamino; OH; optionally substituted C 1 -C 20 alkoxy, optionally substituted C 1 -C 20 alkanoyl; optionally substituted C 1 -C 20 acyloxy; halo; optionally substituted C 1 -C 20 alkylcarboxylamino; cyano; nitro; SO 2 NR′″R″″ where R′″ and R″″ are independently H, C 1 -C 20 alkyl or aryl; SO 2 R′″ where R″″ is H, C 1 -C 20 alkyl or aryl; or SO 3 R′″ where R′″ is H, C 1 -C 20 alkyl or aryl;

R 8 and R 9 independently represent a hydrogen atom, or an optionally substituted C 1 -C 20 linear or branched alkyl; optionally substituted C 2 -C 20 linear or branched alkenyl; optionally substituted C 6 -C 10 aryl; COOR where R is H, optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl, or a pharmaceutically acceptable counter-ion; CONR′R″, where R′ and R″ are independently H, alkoxy, optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl, optionally substituted C 3 -C 10 cycloalkyl or cycloalkenyl or optionally substituted C 6 -C 10 aryl; NH 2 ; C 1 -C 20 alkylamino, bis(alkylamino) or cycloalkylamino; OH; C 1 -C 20 alkoxy; C 1 -C 20 alkanoyl; C 1 -C 20 acyloxy; halo; C 1 -C 20 alkylcarboxylamino; cyano; nitro; SO 2 NR′″R″″ where R′″ and R″″ are independently H, C 1 -C 20 alkyl or aryl; SO 2 R′″ where R′″ is H, C 1 -C 20 alkyl or aryl; or SO 3 R′″ where R′″ is H, C 1 -C 20 alkyl or aryl;

R 10 and R 11 independently represent a hydrogen atom or an optionally substituted C 1 -C 20 linear or branched alkyl; optionally substituted C 2 -C 20 linear or branched alkenyl; optionally substituted C 6 -C 10 aryl; COOR where R represents a hydrogen atom or an optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl, or a pharmaceutically acceptable counter-ion; CONR′R″, where R′ and R′ independently represent a hydrogen atom, optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl; NH 2 ; C 1 -C 20 alkylamino, bis(alkylamino) or cycloalkylamino; OH; C 1 -C 20 alkoxy; C 1 -C 20 alkanoyl; C 1 -C 20 acyloxy; halo; C 1 -C 20 alkylcarboxylamino; cyano; nitro; SO 2 NR′″R″″ where R″″ and R″″ independently represent a hydrogen atom, C 1 -C 20 alkyl or aryl; SO 2 R′″ where R′″ represents a hydrogen atom, C 1 -C 20 alkyl or aryl; or SO 3 R′″ where R′″ represents a hydrogen atom, C 1 -C 20 alkyl or aryl;

R 12 , R 13 , R 18 , R 19 and R 20 independently represent a hydrogen atom; or an optionally substituted C 1 -C 20 linear or branched alkyl; optionally substituted C 2 -C 20 linear or branched alkenyl; optionally substituted C 6 -C 10 aryl; COOR where R represents an optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl, or a pharmaceutically acceptable counter-ion; CONR′R″, where R″ and R″ independently represent a hydrogen atom, optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl; C 1 -C 20 alkanoyl; C 1 -C 20 alkylamido; C 6 -C 20 aroyl; or SO 2 R′″ where R′″ represents a hydrogen atom, C 1 -C 20 alkyl or aryl;

R 12 and R 13 may be absent;

R 14 represents a hydrogen atom, or an optionally substituted C 1 -C 20 linear or branched alkyl including chloroalkyl and fluoroalkyl; optionally substituted C 2 -C 20 linear or branched alkenyl; optionally substituted C 6 -C 10 aryl; COOR where R represents a hydrogen atom, optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl, or a pharmaceutically acceptable counter-ion; CONR′R″, where R′ and R″ independently represent a hydrogen atom, or an optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl; or cyano;

R 15 , R 16 and R 17 independently represent a hydrogen atom, or an optionally substituted C 1 -C 20 linear or branched alkyl including chloroalkyl and fluoroalkyl; optionally substituted C 2 -C 20 linear or branched alkenyl; optionally substituted C 6 -C 10 aryl; COOR where R represents a hydrogen atom, or an optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl, or a pharmaceutically acceptable counter-ion; CONR′R″, where R′ and R″ independently represent a hydrogen atom, an optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl; NH 2 , C 1 -C 20 alkylamino, bis(alkylamino), or cycloalkylamino; OH; C 1 -C 20 alkoxy; C 1 -C 20 alkanoyl; C 1 -C 20 acyloxy; halo; C 1 -C 20 alkylcarboxylamino; cyano; nitro; SO 2 NR′″R″″ where R′″ and R″″ independently represent a hydrogen atom, C 1 -C 20 alkyl or aryl; SO 2 R′″ where R′″ independently represents a hydrogen atom, C 1 -C 20 alkyl or aryl; or SO 3 R′″ where R′″ independently represents a hydrogen atom, C 1 -C 20 alkyl or aryl;

X represents O;

Y independently represents an oxygen atom or sulfur atom;

Z independently represents

OR a , wherein R a represents a hydrogen atom, or an optionally substituted C 1 -C 20 linear or branched alkyl, chloroalkyl or fluoroalkyl, optionally substituted C 2 -C 20 linear or branched alkenyl; optionally substituted C 6 -C 10 aryl; optionally substituted C 6 -C 20 aroyl; optionally substituted C 1 -C 20 alkanoyl; or SO 2 R′″ where R′″ represents a hydrogen atom, C 1 -C 20 alkyl or aryl; or

NR b R c , wherein R b and R c independently represent a hydrogen atom, or an optionally substituted C 1 -C 20 linear or branched alkyl, chloroalkyl or fluoroalkyl; optionally substituted C 2 -C 20 linear or branched alkenyl; optionally substituted C 6 -C 10 aryl; optionally substituted C 3 -C 10 cycloalkyl or cycloalkenyl; COOZ 1 where Z 1 represents an optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl; optionally substituted C 6 -C 20 aroyl; optionally substituted C 1 -C 20 alkanoyl; or SO 2 R′″ where R′″ represents a hydrogen atom, or an C 1 -C 20 alkyl or aryl; or

CR d R e R f , wherein R d , R e and R f independently represent a hydrogen atom, or an optionally substituted C 1 -C 20 linear or branched alkyl, chloroalkyl or fluoroalkyl, optionally substituted C 2 -C 20 linear or branched alkenyl; optionally substituted C 6 -C 10 aryl; optionally substituted C 3 -C 10 cycloalkyl or cycloalkenyl; COOR where R represents a hydrogen atom, or an optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl or optionally substituted C 6 -C 10 aryl, sodium, potassium, calcium, magnesium, ammonium, or tromethamine; NH 2 ; C 1 -C 20 alkylamino, bis(alkylamino) or cycloalkylamino; OH; optionally substituted C 1 -C 20 alkoxy, trifluoromethoxy; optionally substituted C 1 -C 20 alkanoyl; optionally substituted C 1 -C 20 acyloxy; optionally substituted C 6 -C 20 aroyl; halo; cyano; nitro; optionally substituted C 1 -C 20 alkylcarboxylamino; SO 2 NR′″R″″ where R′″ and R′″ independently represent a hydrogen atom, C 1 -C 20 alkyl or aryl; SO 2 R′″ where R′″ independently represents a hydrogen atom, C 1 -C 20 alkyl or aryl; or SO 3 R′″ where R′″ independently represents a hydrogen atom, C 1 -C 20 alkyl or aryl; or

the grouping —C (=Y)Z may represent hydrogen or R 12 or may be absents.

2. The compound according to claim 1 wherein said compound is represented by Formula I.

3. The compound according to claim 2 wherein the bond represented by a dashed line plus a solid line between the carbons with the group R8 and R9 attached is a double-bond.

4. The compound according to claim 3 wherein at least one of R 8 or R 9 represents CONR′R″, wherein R′ and R″ independently represent a hydrogen atom, or an alkoxy, optionally substituted C 1 -C 20 alkyl, optionally substituted C 2 -C 20 alkenyl, optionally substituted C 3 -C 10 cycloalkyl, optionally substituted cycloalkenyl, or optionally substituted C 6 -C 10 aryl.

5. The compound according to claim 2 wherein at least one of R 8 or R 9 represents CONR′R″, wherein each of R′ and R″ represent a hydrogen atom.

6. The compound according to claim 5 wherein R 8 represents a hydrogen atom.

7. The compound according to claim 6 wherein Y represents an oxygen atom.

8. The compound according to claim 2 wherein Z represents NR b R c , wherein R b and R c independently represent a hydrogen atom, optionally substituted C 1 -C 20 linear or branched alkyl, optionally substituted C 6 -C 10 aryl, or optionally substituted C 3 -C 10 cycloalkyl.

9. The compound according to claim 2 wherein R 1 and R 2 independently represent an optionally substituted C 1 -C 4 alkoxy.

10. The compound according to claim 9 wherein the grouping —C(═Y)Z represents hydrogen.

11. The compound 3-(3,5-Dimethoxyphenyl)-N,N-dimethyl-2-{4-[4-(3-oxo-3ureido-propyl)-phenoxy]-phenyl}-acrylamide (13).

12. The compound 2-{4-[4-(2Carbamoylethyl)-phenoxy]phenyl}-3-(3,5-dimethoxyphenyl)-N,N-dimethylacrylamide (31).

13. The compound N,N-Dimethy-2-{4-[4-(3-oxo-3-ureidopropyl)-phenoxyl]-phenyl}-3-pyridin-3-yl-acrylamide (73).

14. The compound 2-{4-[4-(2-Carbamoyl-ethyl)-phenoxy]-phenyl}-N,N-dimethyl-3-pyridin-3-yl-acrylamide (77).

15. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier.

16. A pharmaceutical composition comprising the compound of claim 2 and a pharmaceutically acceptable carrier.

17. The composition of claim 16 , wherein the composition is suitable for oral administration.

Assignments (3)

Continuity (10)