CA2403871A1 - Inhibition of angiogenesis and tumor growth - Google Patents
Inhibition of angiogenesis and tumor growth Download PDFInfo
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Abstract
Compounds which inhibit tumor growth and angiogenesis, of general formula (II) are provided. These compounds include glycyl lysine derivatives bound to a central aromatic linking core.
Claims (40)
1. A compound of structure:
wherein G1 and G2 are each independently -NH-C(O)-O-RI, -NH-C(O)-O-(CH2)v-(C6Ha)-X 1, -NH-C(O)-NH-(CH2)v-(C6Ha)-X 1, -O-C(O)-NH-(CH2)v-(C6H4)-X 1, -O-C(O)-O-(CH2)v-(C6H4)-X 1, or -NH-C(O)-CH2-(C6H4)-X 1; Y 1 and Y 2 are each independently OH, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, phenyl, benzyl, or -NH2; R 1 is C1-C4 alkyl;
X 1 is halo, nitro, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 perfluoroalkyl; Z is -C---C-, -C6H4-, cis -CH=CH-, traps -CH=CH-, cis -CH2 CH=CH-CH2-, traps -CH2-CH=CH-CH2, 1,4-naphthyl, cis-1,3-cyclohexyl, traps-1,3-cyclohexyl, cis-1,4-cyclohexyl, or traps-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or 1; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Y 1 is C1-hydroxyalkyl; and when n is 0, Y 2 is C1-C4 hydroxyalkyl.
wherein G1 and G2 are each independently -NH-C(O)-O-RI, -NH-C(O)-O-(CH2)v-(C6Ha)-X 1, -NH-C(O)-NH-(CH2)v-(C6Ha)-X 1, -O-C(O)-NH-(CH2)v-(C6H4)-X 1, -O-C(O)-O-(CH2)v-(C6H4)-X 1, or -NH-C(O)-CH2-(C6H4)-X 1; Y 1 and Y 2 are each independently OH, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, phenyl, benzyl, or -NH2; R 1 is C1-C4 alkyl;
X 1 is halo, nitro, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 perfluoroalkyl; Z is -C---C-, -C6H4-, cis -CH=CH-, traps -CH=CH-, cis -CH2 CH=CH-CH2-, traps -CH2-CH=CH-CH2, 1,4-naphthyl, cis-1,3-cyclohexyl, traps-1,3-cyclohexyl, cis-1,4-cyclohexyl, or traps-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or 1; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Y 1 is C1-hydroxyalkyl; and when n is 0, Y 2 is C1-C4 hydroxyalkyl.
2. The compound of C1aim 1 wherein G 1 and G 2 are -NH-C(O)-O-(CH2)v-(C6H4)-X 1, A is a covalent bond, and v is 1.
3. The compound of C1aim 2 wherein X 1 is trifluoromethyl.
4. The compound of C1aim 2 wherein Y 1 and Y 2 are OH, m is 1 and n is 1.
5. A compound of structure:
wherein R 2 and R 3 are each independently H, C1-C4 alkyl, phenyl or benzyl; X
and X 3 are each independently halo, vitro, C1-C4 alkoxy, C1-C4 alkyl, or C1-C4 perfluoroalkyl; A is H or a covalent bond; and t is an integer having a value of 0 or 1; with the proviso that when A is H, t is 0 and when A is a covalent bond, t is 1.
wherein R 2 and R 3 are each independently H, C1-C4 alkyl, phenyl or benzyl; X
and X 3 are each independently halo, vitro, C1-C4 alkoxy, C1-C4 alkyl, or C1-C4 perfluoroalkyl; A is H or a covalent bond; and t is an integer having a value of 0 or 1; with the proviso that when A is H, t is 0 and when A is a covalent bond, t is 1.
6. The compound of claim 5 wherein at least one of X 2 and X 3 is para-trifluoromethyl, and A is a covalent bond.
7. The compound of claim 5 wherein at least one of R 2 and R 3 is H, and A is a covalent bond.
8. The compound of claim 5 wherein at least one of R 2 and R 3 is methyl, and A is a covalent bond.
9. The compound of claim 5 wherein X 2 and X 3 are each para-trifluoromethyl, R 2 and R 3 are each methyl, and A is a covalent bond.
10. The compound of claim 5 wherein R 2 is H, and A is H.
11. The compound of claim 5 wherein R 2 is methyl, and A is H.
12. The compound of claim 5 wherein X 2 is para-trifluoromethyl, R 1 is H, and A is H.
13. The compound of structure:
14. A pharmaceutical preparation comprising a compound of structure:
wherein G 1 and G 2 are each independently -NH-C(O)-O-R 1, -NH-C(O)-O-(CH2)v-(C6H4)-X 1, -NH-C(O)-NH-(CH2)v-(C6H4)-X 1, -O-C(O)-NH-(CH2)v-(C6Ha)-X 1, -O-C(O)-O-(CH2)v-(C6Ha)-X 1. or -NH-C(O)-CH2-(C6H4)-X 1; Y 1 and Y 2 are each independently OH, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, phenyl, benzyl, or -NHa; R 1 is C1-C4 alkyl;
X 1 is halo, nitro, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 perfluoroalkyl; Z is -C---- C-, -C6H4-, cis -CH=CH-, traps -CH=CH-, cis -CH2-CH=CH-CH2, traps -CH2-CH=CH-CH2, 1,4-naphthyl, cis-1,3-cyclohexyl, traps-1,3-cyclohexyl, cis-1,4-cyclohexyl, or traps-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or 1; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Y 1 is C1-hydroxyalkyl; and when n is 0, Y 2 is C1-C4 hydroxyalkyl;
in a pharmaceutically acceptable carrier.
wherein G 1 and G 2 are each independently -NH-C(O)-O-R 1, -NH-C(O)-O-(CH2)v-(C6H4)-X 1, -NH-C(O)-NH-(CH2)v-(C6H4)-X 1, -O-C(O)-NH-(CH2)v-(C6Ha)-X 1, -O-C(O)-O-(CH2)v-(C6Ha)-X 1. or -NH-C(O)-CH2-(C6H4)-X 1; Y 1 and Y 2 are each independently OH, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, phenyl, benzyl, or -NHa; R 1 is C1-C4 alkyl;
X 1 is halo, nitro, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 perfluoroalkyl; Z is -C---- C-, -C6H4-, cis -CH=CH-, traps -CH=CH-, cis -CH2-CH=CH-CH2, traps -CH2-CH=CH-CH2, 1,4-naphthyl, cis-1,3-cyclohexyl, traps-1,3-cyclohexyl, cis-1,4-cyclohexyl, or traps-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or 1; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Y 1 is C1-hydroxyalkyl; and when n is 0, Y 2 is C1-C4 hydroxyalkyl;
in a pharmaceutically acceptable carrier.
15. The pharmaceutical preparation of claim 14 wherein G 1 and G 2 are -NH-C(O)-O-(CH2)v-(C6H4)-X 1, A is a covalent bond, and v is 1.
16. The pharmaceutical preparation of claim 15 wherein X 1 is trifluoromethyl.
17. The pharmaceutical preparation of claim 15 wherein Y 1 and Y 2 are OH, m is 1 and n is 1.
bond.
bond.
18. The pharmaceutical preparation of claim 15 wherein X 2 is pare-trifluoromethyl, R 1 is H, and A is H.
19. The pharmaceutical preparation comprising a compound of structure:
in a pharmaceutically acceptable carrier.
in a pharmaceutically acceptable carrier.
20. A method of inhibiting tumor growth in a host which comprises administering to the host m need of such an inhibition a therapeutically effective amount of a compound represented by the formula:
wherein G 1 and G 2 are each independently -NH-C(O)-O-R 1, -NH-C(O)-O-(CH2)v-(C6H4)-X 1, -NH-C(O)-NH-(CH2)v-(C6H4)-X 1, -O-C(O)-NH-(CH2)v-(C6Ha)-X 1, -O-C(O)-O-(CH2)v-(C6H4)-X 1, or -NH-C(O)-CH2-(C6H4)-X 1; Y 1 and Y 2 are each independently OH, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, phenyl, benzyl, or -NH2; R 1 is C1-C4 alkyl;
X 1 is halo, vitro, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 perfluoroalkyl; Z is -C---C-, -C6H4-, cis -CH=CH-, traps -CH=CH-, cis -CH2-CH=CH-CH2, traps -CH2-CH=CH-CH2, 1,4-naphthyl, cis-1, 3-cyclohexyl, traps-1, 3-cyclohexyl, cis-1,4-cyclohexyl, or traps-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or 1; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Y 1 is C1-hydroxyalkyl; and when n is 0, Y 2 is C1-C4 hydroxyalkyl.
wherein G 1 and G 2 are each independently -NH-C(O)-O-R 1, -NH-C(O)-O-(CH2)v-(C6H4)-X 1, -NH-C(O)-NH-(CH2)v-(C6H4)-X 1, -O-C(O)-NH-(CH2)v-(C6Ha)-X 1, -O-C(O)-O-(CH2)v-(C6H4)-X 1, or -NH-C(O)-CH2-(C6H4)-X 1; Y 1 and Y 2 are each independently OH, C1-C4 alkyl, C1-C4 hydroxyalkyl, C1-C4 alkoxy, phenyl, benzyl, or -NH2; R 1 is C1-C4 alkyl;
X 1 is halo, vitro, C1-C4 alkyl, C1-C4 alkoxy, or C1-C4 perfluoroalkyl; Z is -C---C-, -C6H4-, cis -CH=CH-, traps -CH=CH-, cis -CH2-CH=CH-CH2, traps -CH2-CH=CH-CH2, 1,4-naphthyl, cis-1, 3-cyclohexyl, traps-1, 3-cyclohexyl, cis-1,4-cyclohexyl, or traps-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or 1; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Y 1 is C1-hydroxyalkyl; and when n is 0, Y 2 is C1-C4 hydroxyalkyl.
21. The method of inhibiting tumor growth of claim 20 wherein G 1 and G 2 are -NH-C(O)-O-(CH2)v-(C6H4)-X 1, A is a covalent bond, and v is 1.
22. The method of inhibiting tumor growth of claim 21 wherein X 1 is trifluoromethyl.
23. The method of inhibiting tumor growth of claim 21 wherein Y 1 and Y 2 are OH, m is 1 and n is 1.
24. The method of inhibiting tumor growth according to claim 20 wherein the administering comprises intraperitoneal, subcutaneous, intravenous, transdermal, intrasynovial, intramuscular or oral administration.
25. A method of inhibiting tumor growth in. a host which comprises administering to the host in need of such an inhibition a therapeutically effective amount of a compound represented by the formula:
26. The method of inhibiting tumor growth according to claim 25 wherein the administering comprises intraperitoneal, subcutaneous, intravenous, trarisdermal, intrasynovially, intramuscular or oral administration.
27. A method of inhibiting angiogenesis in a tumor tissue which comprises administering to the tumor tissue an angiogenesis inhibiting effective amount of a compound represented by the formula:
wherein G1 and G2 are each independently -NH-C(O)-O-R1, -NH-C(O)-O-(CH2) (C6H4)-X1, -NH-C(O)-NH-(CH2) (C6H4)-X1, -O-C(O)-NH-(CH2) (C6H4)-X1, -O-C(O)-O-(CH2)v (C6H4)-X1, or -NH-C(O)-CH2 (C6H4)-X1; Y1 and Y2 are each independently OH, Ci- C4. alkyl, C1- C4 hydroxyalkyl, C1- C4 alkoxy, phenyl, benzyl, or -NH2; R1 is C1- C4 alkyl;
X1 is halo, vitro, C1- C4 alkyl, C1- C4 alkoxy, or C1- C4 perfluoroalkyl; Z is -C=C-, -C6H4 , cis -CH = CH-, traps -CH = CH-, cis -CH2 CH = CH-CH2 , trans -CH2-CH=CH-CH2-, 1,4-naphthyl, cis-1,3-cyclohexyl, traps-1,3-cyclohexyl, cis 1,4-cyclohexyl, or trans-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or 1; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Yi is Cl -hydroxyalkyl; and when n is 0, Y2 is C1- C4 hydroxyalkyl.
wherein G1 and G2 are each independently -NH-C(O)-O-R1, -NH-C(O)-O-(CH2) (C6H4)-X1, -NH-C(O)-NH-(CH2) (C6H4)-X1, -O-C(O)-NH-(CH2) (C6H4)-X1, -O-C(O)-O-(CH2)v (C6H4)-X1, or -NH-C(O)-CH2 (C6H4)-X1; Y1 and Y2 are each independently OH, Ci- C4. alkyl, C1- C4 hydroxyalkyl, C1- C4 alkoxy, phenyl, benzyl, or -NH2; R1 is C1- C4 alkyl;
X1 is halo, vitro, C1- C4 alkyl, C1- C4 alkoxy, or C1- C4 perfluoroalkyl; Z is -C=C-, -C6H4 , cis -CH = CH-, traps -CH = CH-, cis -CH2 CH = CH-CH2 , trans -CH2-CH=CH-CH2-, 1,4-naphthyl, cis-1,3-cyclohexyl, traps-1,3-cyclohexyl, cis 1,4-cyclohexyl, or trans-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or 1; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Yi is Cl -hydroxyalkyl; and when n is 0, Y2 is C1- C4 hydroxyalkyl.
28. The method claim 27 wherein G1 and G2 are -NH-C(O)-O-(CH2)v-(C6H4)-X1, A is a covalent bond, and v is 1.
29. The method of claim 28 wherein X1 is trifluoromethyl.
30. The method of claim 28 wherein Y1 and Y2 are OH, m is 1 and n is 1.
31. The method of inhibiting tumor growth according to claim 27 wherein the administering comprises intraperitoneal, subcutaneous, intravenous, transdermal, intrasynovial, intramuscular or oral administration.
32. A method of inducing apoptosis in a tumor cells which comprises administering to the tumor cells a therapeutically effective amount of a compound represented by the formula:
wherein G1 and G2 are each independently -NH-C(O)-O-R1, -NH-C(O)-O-(CH2)v (C6H4)-X1, -NH-C(O)-NH-(CH2)v (C6H4)-X1, -O-C(O)-NH-(CH2)v (C6H4)-X1 -O-C(O)-O-(CH2)v (C6Ha)-X1 s or -NH-C(O)-CH2-(C6H4)-X1; Y1 and Y2 are each independently OH, C1- C4 alkyl, C1- C4 hydroxyalkyl, C1- C4 alkoxy, phenyl, benzyl, or -NH2; R1 is C1- C4 alkyl;
X1 is halo, vitro, C1-C4 alkyl, C1- C4 alkoxy, or C1- C4 perfluoroalkyl; Z is -C=C-, -C6H4 , cis -CH = CH-, trans -CH = CH-, cis -CH2 CH = CH-CH2 , trans -CH2 CH=CH-CH2 , 1,4-naphthyl, cis-1,3-cyclohexyl, trans-1,3-cyclohexyl, cis-1,4-cyclohexyl, or trans-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or l; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Y1 is C1 -hydroxyalkyl; and when n is 0, Y2 is C1 - C4 hydroxyalkyl.
wherein G1 and G2 are each independently -NH-C(O)-O-R1, -NH-C(O)-O-(CH2)v (C6H4)-X1, -NH-C(O)-NH-(CH2)v (C6H4)-X1, -O-C(O)-NH-(CH2)v (C6H4)-X1 -O-C(O)-O-(CH2)v (C6Ha)-X1 s or -NH-C(O)-CH2-(C6H4)-X1; Y1 and Y2 are each independently OH, C1- C4 alkyl, C1- C4 hydroxyalkyl, C1- C4 alkoxy, phenyl, benzyl, or -NH2; R1 is C1- C4 alkyl;
X1 is halo, vitro, C1-C4 alkyl, C1- C4 alkoxy, or C1- C4 perfluoroalkyl; Z is -C=C-, -C6H4 , cis -CH = CH-, trans -CH = CH-, cis -CH2 CH = CH-CH2 , trans -CH2 CH=CH-CH2 , 1,4-naphthyl, cis-1,3-cyclohexyl, trans-1,3-cyclohexyl, cis-1,4-cyclohexyl, or trans-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or l; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Y1 is C1 -hydroxyalkyl; and when n is 0, Y2 is C1 - C4 hydroxyalkyl.
33. The method of claim 32 wherein G1 and G2 are NH-C(O)-O-(CH2)v (C6H4)-X1, A is a covalent bond, and v is 1.
34. The method of claim 33 wherein X1 is trifluoromethyl.
35. The method of claim 33 wherein Y1 and Y2 are OH, m is 1 and n is 1.
36. The method of inhibiting tumor growth according to claim 32 wherein the administering comprises intraperitoneal, subcutaneous, intravenous, transdermal, intrasynovially, intramuscular or oral administration.
37. A method of inhibiting the interaction of MMP2 with integrin .alpha. v .beta. v in a host cell which comprises contacting the integrin with an interaction inhibiting amount of a compound represented by the formula:
wherein G1 and G2 are each independently -NH-C(O)-O-R1, -NH-C(O)-O-(CH2)v (C6H4)-X1, -NH-C(O)-NH-(CH2)v (C6H4)-X1, -O-C(O)-NH-(CH2)v (C6H4)-X1, -O-C(O)-O-(CH2)v (C6H4)-X1, or -NH-C(O)-CH2-(C6H4)-X1; Y1 and Y2 are each independently OH, C1- C4 alkyl, C1- C4 hydroxyalkyl, C1- C4 alkoxy, phenyl, benzyl, or -NH2; R1 is C1- C4 alkyl;
X1 is halo, vitro, C1- C4 alkyl, C1- C4 alkoxy, or C1- C4 perfluoroalkyl; Z is -C=C-, -C6H4-, cis -CH = CH-, trans -CH = CH-, cis -CH2 CH = CH-CH2 , trans -CH2 CH=CH-CH2 , 1,4-naphthyl, cis-1,3-cyC1ohexyl, trans-1,3-cyclohexyl, cis-1,4-cyC1ohexyl, or trans-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or 1; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Y1 is C1-hydroxyalkyl; and when n is 0, Y2 is C1- C4 hydroxyalkyl.
wherein G1 and G2 are each independently -NH-C(O)-O-R1, -NH-C(O)-O-(CH2)v (C6H4)-X1, -NH-C(O)-NH-(CH2)v (C6H4)-X1, -O-C(O)-NH-(CH2)v (C6H4)-X1, -O-C(O)-O-(CH2)v (C6H4)-X1, or -NH-C(O)-CH2-(C6H4)-X1; Y1 and Y2 are each independently OH, C1- C4 alkyl, C1- C4 hydroxyalkyl, C1- C4 alkoxy, phenyl, benzyl, or -NH2; R1 is C1- C4 alkyl;
X1 is halo, vitro, C1- C4 alkyl, C1- C4 alkoxy, or C1- C4 perfluoroalkyl; Z is -C=C-, -C6H4-, cis -CH = CH-, trans -CH = CH-, cis -CH2 CH = CH-CH2 , trans -CH2 CH=CH-CH2 , 1,4-naphthyl, cis-1,3-cyC1ohexyl, trans-1,3-cyclohexyl, cis-1,4-cyC1ohexyl, or trans-1,4-cyclohexyl; A is H or a covalent bond; m and n are each independently an integer having a value of 0 or 1; t is an integer having a value of 0 or 1; and v is an integer having a value of 1 or 2; with provisos that when A is H, t is 0; when A is a covalent bond, t is 1; when m is 0, Y1 is C1-hydroxyalkyl; and when n is 0, Y2 is C1- C4 hydroxyalkyl.
38. The method of C1aim 37 wherein G1 and G2 are -NH-C(O)-O-(CH2)v (C6H4)-X1, A is a covalent bond, and v is 1.
39. The method of Claim 38 wherein X1 is trifluoromethyl.
40. The method of Claim 38 wherein Y1 and Y2 are OH, m is 1 and n is 1.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| US19226000P | 2000-03-27 | 2000-03-27 | |
| US60/192,260 | 2000-03-27 | ||
| PCT/US2001/009756 WO2001072699A1 (en) | 2000-03-27 | 2001-03-27 | Inhibition of angiogenesis and tumor growth |
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| Publication Number | Publication Date |
|---|---|
| CA2403871A1 true CA2403871A1 (en) | 2001-10-04 |
| CA2403871C CA2403871C (en) | 2010-05-11 |
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| Application Number | Title | Priority Date | Filing Date |
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| CA002659030A Abandoned CA2659030A1 (en) | 2000-03-27 | 2001-03-27 | Methods for inhibiting angiogenesis and tumor growth |
| CA002403630A Expired - Fee Related CA2403630C (en) | 2000-03-27 | 2001-03-27 | Methods for inhibiting angiogenesis and tumor growth |
| CA2403871A Expired - Fee Related CA2403871C (en) | 2000-03-27 | 2001-03-27 | Inhibition of angiogenesis and tumor growth |
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| CA002659030A Abandoned CA2659030A1 (en) | 2000-03-27 | 2001-03-27 | Methods for inhibiting angiogenesis and tumor growth |
| CA002403630A Expired - Fee Related CA2403630C (en) | 2000-03-27 | 2001-03-27 | Methods for inhibiting angiogenesis and tumor growth |
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| EP (2) | EP1272173A4 (en) |
| JP (2) | JP2003528850A (en) |
| KR (2) | KR100767616B1 (en) |
| CN (2) | CN1229339C (en) |
| AU (4) | AU5101801A (en) |
| CA (3) | CA2659030A1 (en) |
| CZ (2) | CZ20023510A3 (en) |
| HU (2) | HUP0301621A3 (en) |
| MX (2) | MXPA02009510A (en) |
| NO (2) | NO328969B1 (en) |
| PL (2) | PL358272A1 (en) |
| RU (2) | RU2276133C2 (en) |
| SK (2) | SK14852002A3 (en) |
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| ZA (2) | ZA200208628B (en) |
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| ES2315721T5 (en) | 2003-10-23 | 2012-08-24 | Otsuka Pharmaceutical Co., Ltd. | Formulation of sterile controlled-release injectable aripiprazole and procedure |
| UA97286C2 (en) | 2007-07-31 | 2012-01-25 | Оцука Фармасьютикал Ко., Лтд. | Method for producing an aripiprazole suspension and freeze-dried formulation |
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| GB8311286D0 (en) * | 1983-04-26 | 1983-06-02 | Searle & Co | Carboxyalkyl peptide derivatives |
| JPH05125029A (en) | 1991-11-06 | 1993-05-21 | Yamanouchi Pharmaceut Co Ltd | New amide compound or its salt |
| GB9308695D0 (en) * | 1993-04-27 | 1993-06-09 | Celltech Ltd | Peptidyl derivatives |
| GB9405076D0 (en) * | 1994-03-16 | 1994-04-27 | Inst Of Ophtalmology | A medical use of matrix metalloproteinase inhibitors |
| AUPO104496A0 (en) * | 1996-07-17 | 1996-08-08 | Biomolecular Research Institute Limited | Angiogenic inhibitory compounds |
| KR20000068415A (en) * | 1996-09-04 | 2000-11-25 | 로즈 암스트롱, 크리스틴 에이. 트러트웨인 | Compounds for and a Method of Inhibiting Matrix Metalloproteinase |
| EP0968423A4 (en) * | 1997-02-07 | 2002-10-30 | Scripps Research Inst | Convergent synthesis of combinatorial library |
| KR100596109B1 (en) * | 1998-03-27 | 2006-07-05 | 제넨테크, 인크. | Antagonists for Treatment of CD11/CD18 Adhesion Receptor Mediated Disorders |
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2001
- 2001-03-27 HU HU0301621A patent/HUP0301621A3/en unknown
- 2001-03-27 AU AU5101801A patent/AU5101801A/en active Pending
- 2001-03-27 KR KR1020027012724A patent/KR100767616B1/en not_active IP Right Cessation
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