1. A composite dressing comprising:
a first polymeric layer;
a second polymeric layer disposed on at least one surface of the first polymeric layer; and
a metal oxide distributed in one selected from a group consisting of in the first polymeric layer, on the at least one surface of the first polymeric layer and a combination thereof.
2. A composite dressing as claimed in claim 1 further comprising a pharmaceutical active material distributed in one selected from a group consisting of in the second polymeric layer, on at least one air contacting surface of the second polymeric layer and a combination thereof.
3. A composite dressing as claimed in claim 2 wherein the pharmaceutical active material is a non-steroid anti-inflammatory drug.
4. A composite dressing as claimed in claim 1 wherein the first polymeric layer is made by a cross-linking reaction and has a cross-linked structure.
5. A composite dressing as claimed in claim 1 wherein the first polymeric layer is made of a cross-linkable polymer containing an amine group.
6. A composite dressing as claimed in claim 1 wherein the first polymeric layer is made of at least one selected from a group consisting of polyurethane, polyester, polyethylene, polyimide, polyamide, polyamide-imide, chitosan, polysaccharide, polyvinylpyrrolidone, cellulose, polylactic acid, and polyether.
7. A composite dressing as claimed in claim 1 wherein the second polymeric layer is made by a cross-linking reaction and has a cross-linked structure.
8. A composite dressing as claimed in claim 1 wherein the second polymeric layer is biocompatible.
9. A composite dressing as claimed in claim 8 wherein the second polymeric layer is made of at least one selected from a group consisting of chitosan, sodium alginate, polysaccharide, polyvinylpyrrolidone, poly-2-hydroxyethyl methacrylate, polyvinyl alcohol, cellulose, hyaluronic acid, collagen, and polylactic acid.
10. A composite dressing as claimed in claim 1 wherein the second polymeric layer is made of a hydrogel.
11. A composite dressing as claimed in claim 1 wherein the first and the second polymeric layers are made of different materials.
12. A composite dressing as claimed in claim 1 wherein the first and the second polymeric layers are made of the same material.
13. A composite dressing as claimed in claim 1 wherein the first and the second polymeric layers are waterproof and moisture-permeable.
14. A composite dressing as claimed in claim 1 wherein the first and the second polymeric layers have elasticity and extensibility.
15. A composite dressing as claimed in claim 1 wherein the second polymeric layer is distributed on at least one surface of the first polymeric layer by a coating method.
16. A composite dressing as claimed in claim 1 wherein the second polymeric layer is distributed on at least one surface of the first polymeric layer by a dipping method.
17. A composite dressing as claimed in claim 1 wherein the metal oxide comprises one selected from a group consisting of an aluminum oxide, a magnesium oxide, and an iron oxide.
18. A composite dressing as claimed in claim 1 wherein the metal oxide has a weight percentage of 0.1% to 40% relative to a total weight of the first polymeric layer and the metal oxide.
19. A composite dressing comprising:
a first polymeric layer;
a second polymeric layer strengthening the first polymeric layer; and
a metal oxide distributed in one selected from a group consisting of in the first polymeric layer, on the at least one surface of the first polymeric layer and a combination thereof.
20. A composite dressing as claimed in claim 19 wherein the second polymeric layer is disposed in one of inside the first polymeric layer and on a surface of the first polymeric layer.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A compound having the Formula:
and pharmaceutically acceptable salts and prodrugs thereof, where
X is N;
Y is NR15, O, S, S(O), S(O)2, C(O) or CH2;
Z is N;
R1, R2, R8, and R9 are independently hydrogen, hydroxy, halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, \u2014SR11, \u2014OR3, \u2014C(O)R3, \u2014C(O)OR3, \u2014NR4C(O)OR6, \u2014OC(O)R3, \u2014NR4SO2R6, \u2014SO2NR3R4, \u2014NR4C(O)R3, \u2014C(O)NR3R4, \u2014NR5C(O)NR3R4, \u2014NR5C(NCN)NR3R4, \u2014NR3R4, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, \u2014S(O)j(C1-C6 alkyl), \u2014S(O)j(CR4R5)m-aryl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, \u2014O(CR4R5)m-aryl, \u2014NR4(CR4R5)m-aryl, \u2014O(CR4R5)m-heteroaryl, \u2014NR4(CR4R5)m-heteroaryl, \u2014O(CR4R5)m-heterocyclyl or \u2014NR4(CR4R5)m-heterocyclyl, wherein any of said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo (with the proviso that it is not substituted on an aryl or heteroaryl), halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, \u2014NR4SO2R6, \u2014SO2NR3R4, \u2014C(O)R3, \u2014C(O)OR3, \u2014OC(O)R3, \u2014NR4C(O)OR6, \u2014NR4C(O)R3, \u2014C(O)NR3R4, \u2014NR3R4, \u2014NR5C(O)NR3R4, \u2014NR5C(NCN)NR3R4, \u2014OR3, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl, and wherein said cycloalkyl, heterocycloalkyl, aryl or heteroaryl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, NR3R4 and OR3;
R7 is hydrogen, trifluoromethyl, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, or heterocyclylalkyl, wherein any of said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo (with the proviso that it is not substituted on an aryl or heteroaryl), halogen, cyano, nitro, trifluoromethyl, difluoromethyl, fluoromethyl, fluoromethoxy, difluoromethoxy, trifluoromethoxy, azido, \u2014NR11SO2R14, \u2014SO2NR11R12, \u2014C(O)R11, C(O)OR11, \u2014OC(O)R11, \u2014NR11C(O)OR14, \u2014NR11C(O)R12, \u2014C(O)NR11R12, \u2014SR11, \u2014S(O)R14, \u2014SO2R14, \u2014NR11R12, \u2014NR11C(O)NR12R13, \u2014NR11C(NCN)NR12R13, \u2014OR11, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl, and wherein said cycloalkyl, heterocycloalkyl, aryl or heteroaryl rings may be further substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, NR3R4 and OR3;
R3 is hydrogen, trifluoromethyl, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-C10 cycloalkyl, C3-C10 cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl, heterocyclylalkyl, phosphate or an amino acid residue, wherein any of said alkyl, alkenyl, alkynyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo (with the proviso that it is not substituted on an aryl or heteroaryl), halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, \u2014NR11SO2R14, \u2014SO2NR11R12, \u2014C(O)R11, C(O)OR11, \u2014OC(O)R11, \u2014NR11C(O)OR14, \u2014NR11C(O)R12, \u2014C(O)NR11R12, \u2014SR11, \u2014S(O)R14, \u2014SO2R14, \u2014NR11R12, \u2014NR11C(O)NR12R13, \u2014NR11C(NCN)NR12R13, \u2014OR11, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
or R3 and R4 together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring, wherein any of said carbocyclic, heteroaryl or heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, \u2014NR11SO2R14, \u2014SO2NR11R12, \u2014C(O)R11, C(O)OR11, \u2014OC(O)R11, \u2014NR11C(O)OR14, \u2014NR11C(O)R12, \u2014C(O)NR11R12, \u2014SR11, \u2014S(O)R14, \u2014SO2R14, \u2014NR11R12, \u2014NR11C(O)NR12R13, \u2014NR11C(NCN)NR12R13, \u2014OR11, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
R4 and R5 independently are hydrogen or C1-C6 alkyl, or
R4 and R5 together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring, wherein said alkyl or any of said carbocyclic, heteroaryl and heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, \u2014NR11SO2R14, \u2014SO2NR11R12, \u2014C(O)R11, C(O)OR11, \u2014OC(O)R11, \u2014NR11C(O)OR14, \u2014NR11C(O)R12, \u2014C(O)NR11R12, \u2014SR11, \u2014S(O)R14, \u2014SO2R14, \u2014NR11R12, \u2014NR11C(O)NR12R13, \u2014NR11C(NCN)NR12R13, \u2014OR11, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
R6 is trifluoromethyl, C1-C10 alkyl, C3-C10 cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl or heterocyclylalkyl, wherein any of said alkyl, cycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl and heterocyclylalkyl are optionally substituted with one or more groups independently selected from oxo (with the proviso that it is not substituted on an aryl or heteroaryl), halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, \u2014NR11SO2R14, \u2014SO2NR11R12, \u2014C(O)R11, C(O)OR11, \u2014OC(O)R11, \u2014NR11C(O)OR14, \u2014NR11C(O)R12, \u2014C(O)NR11R12, \u2014SR11, \u2014S(O)R14, \u2014SO2R14, \u2014NR11R12, \u2014NR11C(O)NR12R13, \u2014NR11C(NCN)NR12R13, \u2014OR11, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
R11, R12 and R13 independently are hydrogen, lower alkyl, lower alkenyl, aryl or arylalkyl, and R14 is lower alkyl, lower alkenyl, aryl or arylalkyl;
or any two of R11, R12, R13 or R14 together with the atom to which they are attached form a 4 to 10 membered carbocyclic, heteroaryl or heterocyclic ring, wherein any of said alkyl, alkenyl, aryl, arylalkyl carbocyclic rings, heteroaryl rings or heterocyclic rings are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, trifluoromethyl, difluoromethoxy, trifluoromethoxy, azido, aryl, heteroaryl, arylalkyl, heteroarylalkyl, heterocyclyl, and heterocyclylalkyl;
W is heteroaryl, heterocyclyl, \u2014C(O)OR3, \u2014C(O)NR3R4, \u2014C(O)NR4OR3, \u2014C(O)R4OR3, \u2014C(O)NR4SO2R3, \u2014C(O)(C3-C10 cycloalkyl), \u2014C(O)(C1-C10 alkyl), \u2014C(O)(aryl), \u2014C(O)(heteroaryl), \u2014C(O)(heterocyclyl) or CR3OR3, wherein any of said heteroaryl, heterocyclyl, \u2014C(O)OR3, \u2014C(O)NR3R4, \u2014C(O)NR4OR3, \u2014C(O)R4OR3, \u2014C(O)NR4SO2R3, \u2014C(O)(C3-C10 cycloalkyl), \u2014C(O)(C1-C10 alkyl), \u2014C(O)(aryl), \u2014C(O)(heteroaryl), \u2014C(O)(heterocyclyl) and CR3OR3 are optionally substituted with one or more groups independently selected from halogen, cyano, nitro, azido, \u2014NR3R4, \u2014OR3, C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, cycloalkyl and heterocycloalkyl, wherein any of said C1-C10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, cycloalkyl and heterocycloalkyl are optionally substituted with 1 or more groups independently selected from \u2014NR3R4 and \u2014OR3;
R15 is hydrogen, halogen, methyl, fluoromethyl, difluoromethyl, trifluoromethyl or ethyl;
m is 0, 1, 2, 3, 4 or 5; and
j is 0, 1 or 2.
2. The compound of claim 1, where Y is NH.
3. The compound of claim 2, where R9 is hydrogen, halogen, methyl, fluoromethyl, difluoromethyl, trifluoromethyl or ethyl.
4. The compound of claim 3, where W is selected from heteroaryl, C(O)OR3, C(O)NR3R4, C(O)NR4OR3 and C(O)NR4S(O)2R3, wherein any of said heteroaryl, C(O)OR3, C(O)NR3R4, C(O)NR4OR3 or C(O)NR4S(O)2R3 are optionally substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, amino, aminomethyl, dimethylamino, aminoethyl, diethylamino, ethoxy, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl, wherein any of said C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, cycloalkyl or heterocycloalkyl can be further optionally substituted with one or more groups selected from NR3R4 and OR3.
5. The compound of claim 3, where W is selected from C(O)OR3, C(O)NHR3, and C(O)NHOR3, wherein any of said C(O)OR3, C(O)NHR3, and C(O)NHOR3 are optionally substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, amino, aminomethyl, dimethylamino, aminoethyl, diethylamino, ethoxy, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl, wherein any of said C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, cycloalkyl or heterocycloalkyl can be further optionally substituted with one or more groups selected from NR3R4 and OR3; and
R3 is selected from hydrogen, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl and C3-C6 heterocycloalkyl, wherein any of said C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, cycloalkyl or heterocycloalkyl are optionally substituted with one or more groups selected from NR3R4 and OR3.
6. The compound of claim 5, where R7 is C1-C4 alkyl, C2-C4 alkenyl or C2-C4 alkynyl, wherein said C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl, may be optionally substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy, amino, aminomethyl, dimethylamino, aminoethyl, diethylamino, ethoxy, cycloalkyl, heterocycloalkyl, aryl and heteroaryl, wherein said cycloalkyl, heterocycloalkyl, aryl or heteroaryl rings may be optionally substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, NR3R4 and OR3.
7. The compound of claim 6, where R1 and R2 are independently hydrogen, halogen, methyl, fluoromethyl, difluoromethyl, trifluoromethyl or ethyl; and R8 is halogen, hydroxyl, cyano, nitro, azido, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, amino, aminomethyl, dimethylamino, aminoethyl, diethylamino, ethyl, ethoxy or SR11.
8. The compound of claim 7, where R1 is halogen or methyl, R2 is hydrogen and R8 is hydrogen, halogen, methyl, fluoromethyl, difluoromethyl, trifluoromethyl or SR11.
9. The compound of claim 8, where R1 is halogen, R8 is halogen, R9 is alkyl or halogen, and R2 is in the position adjacent to Y, where R2 is hydrogen.
10. The compound of claim 3, where W is selected from
11. The compound of claim 10, where R7 is C1-C4 alkyl, C2-C4 alkenyl or C2-C4 alkynyl, wherein said C1-C4 alkyl, C2-C4 alkenyl and C2-C4 alkynyl may be optionally substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy, amino, aminomethyl, dimethylamino, aminoethyl, diethylamino, ethoxy, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein said cycloalkyl, heterocycloalkyl, aryl or heteroaryl rings may be optionally substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, azido, fluoromethyl, difluoromethyl, trifluoromethyl, C1-C4 alkyl, C2-C4 alkenyl, C2-C4 alkynyl, C3-C6 cycloalkyl, C3-C6 heterocycloalkyl, NR3R4 and OR3.
12. The compound of claim 11, where R1 and R2 are independently hydrogen, halogen, methyl, fluoromethyl, difluoromethyl, trifluoromethyl or ethyl; and R8 is halogen, hydroxyl, cyano, nitro, azido, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, amino, aminomethyl, dimethylamino, aminoethyl, diethylamino, ethyl, ethoxy or SR11.
13. The compound of claim 12, where R1 is halogen or methyl, R2 is hydrogen and R8 is hydrogen, halogen, methyl, fluoromethyl, difluoromethyl, trifluoromethyl or SR11.
14. The compound of claim 13, where R1 is halogen, R2 is hydrogen, R8 is halogen, R9 is alkyl or halogen, and R2 is in the position adjacent to Y, where R2 is hydrogen.
15. A composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
16. A composition comprising a compound of claim 5 and a pharmaceutically acceptable carrier.
17. A composition comprising a compound of claim 10 and a pharmaceutically acceptable carrier.
18. A method for preparing a compound of formula 7
wherein
R1, R2 and R9 are independently hydrogen, halogen, methyl, fluoromethyl, difluoromethyl, trifluoromethyl or ethyl;
R4 is hydrogen or C1-C6 alkyl;
R3 and R7 are independently alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, wherein said alkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl may be optionally substituted with one or more groups selected from halogen, hydroxyl, cyano, nitro, amino, azido, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy, amino, aminomethyl, dimethylamino, aminoethyl, diethylamino, ethoxy, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; and
R8 is halogen, hydroxyl, cyano, nitro, azido, methyl, fluoromethyl, difluoromethyl, trifluoromethyl, methoxy, fluoromethoxy, difluoromethoxy, trifluoromethoxy, amino, aminomethyl, dimethylamino, aminoethyl, diethylamino, SR1, ethyl, or ethoxy;
said method comprising:
(a) reacting a compound of formula 5
with an aniline derivative to provide a compound of formula 6
(b) reacting a compound of formula 6 with an amine to provide a compound of formula 7.