1. A compound of Formula (I)
wherein
A is thienyl or C5-7cycloalkyl;
R1 is one to three substituents selected from the group consisting of hydrogen, C1-4alkyl, C1-4alkoxy, fluoro, chloro, and hydroxy;
L is \u2014Z\u2014(CH2)n\u2014 or \u2014CH2\u2014;
n is 0 or 1;
Z is NR3;
R2 is hydrogen, C1-4alkyl, C1-4alkoxy, trifluoromethyl, chloro, fluoro, bromo, carboxy, or C1-4alkoxycarbonyl;
R3 is hydrogen or C1-3alkyl;
R4 is hydrogen or C1-4alkyl;
R5 is isoquinolinyl; wherein R5 is optionally substituted with 1 to 2 substituents independently selected from the group consisting of C1-4alkyl, hydroxy, C1-4alkoxy, trifluoromethyl, chloro, fluoro, bromo, carboxy, C1-4alkoxycarbonyl, and cyano;
and enantiomers, diastereomers, or a pharmaceutically acceptable salts thereof.
2. The compound according to claim 1 wherein A is cyclopentyl or cyclohexyl.
3. The compound according to claim 1 wherein R1 is one to two substituents selected from the group consisting of hydrogen, C1-4alkyl, C1-4alkoxy, fluoro, chloro, and hydroxy.
4. The compound according to claim 3 wherein R1 is one to two substituents selected from the group consisting of hydrogen, C1-3alkyl, C1-3alkoxy, fluoro, and chloro.
5. The compound according to claim 4 wherein R1 is one to two substituents selected from the group consisting of hydrogen, methyl, fluoro, and chloro.
6. The compound according to claim 1 wherein L is \u2014Z\u2014(CH2)n\u2014 or \u2014CH2\u2014; wherein n is 0 or 1; and Z is NR3.
7. The compound according to claim 6 wherein L is \u2014Z\u2014(CH2)n\u2014; wherein n is 0; and Z is NR3.
8. The compound according to claim 7 wherein L is \u2014Z\u2014(CH2)n\u2014; wherein n is 0; and Z is NR3.
9. The compound according to claim 1 wherein R2 is hydrogen, C1-4alkyl, trifluoromethyl, chloro, or bromo.
10. The compound according to claim 1 wherein R2 is t-butyl, trifluoromethyl, chloro, or bromo.
11. The compound according to claim 1 wherein R3 is hydrogen or methyl.
12. The compound according to claim 1 wherein R3 is hydrogen.
13. The compound according to claim 1 wherein R4 is hydrogen.
14. The compound according to claim 1 wherein R5 is isoquinolinyl; wherein R5 is optionally substituted with one to two substituents independently selected from the group consisting of C1-4alkyl, C1-4alkoxy, and fluoro.
15. The compound according to claim 14 wherein R5 is isoquinolinyl; wherein R5- is optionally substituted with one C1-4alkyl substituent.
16. The compound according to claim 1 wherein R5 is isoquinolin-5-yl.
17. A compound of Formula (I)
wherein
A is cyclopentyl, or cyclohexyl;
R1 is one to two substituents selected from the group consisting of hydrogen, C1-4alkyl, C1-4alkoxy, fluoro, chloro, and hydroxyl;
L is \u2014Z\u2014(CH2)n\u2014 or \u2014CH2\u2014; wherein n is 0 or 1; and Z is NR3;
R2 is hydrogen, C1-4alkyl, trifluoromethyl, chloro, or bromo;
R3 is hydrogen or methyl;
R4 is hydrogen;
and
R5 is isoquinolinyl; wherein R5 is optionally substituted with 1-2 substituents independently selected from the group consisting of C1-4alkyl, C1-4 alkoxy, and fluoro;
and enantiomers, diastereomers, or a pharmaceutically acceptable salt thereof.
18. A compound of Formula (I)
Formula (I) selected from the group consisting of
a compound of Formula (I) wherein A is cyclopentyl, R1 is H, R2 is 4-trifluoromethyl, L is \u2014Z\u2014(CH2)n\u2014, Z is NR3, R3 is H, n is 0, R4 is H, and R5 is isoquinolin-5-yl;
a compound of Formula (I) wherein A is cyclohexyl, R1 is H, R2 is 4-trifluoromethyl, L is \u2014Z\u2014(CH2)n\u2014, Z is NR3, R3 is H, n is 0, R4 is H, and R5 is isoquinolin-5-yl;
and enantiomers, diastereomers, and pharmaceutically acceptable salts thereof.
19. A pharmaceutical composition comprising a compound of claim 1 and at least one of a pharmaceutically acceptable carrier, a pharmaceutically acceptable excipient, and a pharmaceutically acceptable diluent.
20. The pharmaceutical composition of claim 19, wherein the composition is a solid oral dosage form.
21. A pharmaceutical composition of claim 19, wherein the composition is a syrup, an elixir, or a suspension.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
That which is claimed is:
1. A method for forming a bright metallized laminate, comprising:
applying a polyvinylidene difluoride-containing film to a polymeric substrate;
depositing a discontinuous layer of indium islands upon the polyvinylidene difluoride-containing film;
placing a polymeric film onto the discontinuous layer of indium islands; and
press polishing the polyvinylidene difluoride-containing film and the discontinuous indium layer.
2. A method according to claim 1, wherein the step of applying the polyvinylidene difluoride-containing film to the polymeric substrate comprises casting the polyvinylidene difluoride-containing film onto the polymeric substrate.
3. A method according to claim 2, wherein the step of casting the polyvinylidene difluoride-containing film onto the polymeric substrate comprises a technique selected from the group consisting of a knife-over roll coating process, a reverse roll coating process, and a slot die coating process.
4. A method according to claim 1, wherein the step of press polishing the polyvinylidene difluoride-containing film and the discontinuous indium layer comprises pressing the polyvinylidene difluoride-containing film and the discontinuous indium layer between rollers.
5. A method according to claim 1, further comprising:
removing the polymeric film from the discontinuous indium layer after the press polishing step; and
placing an adhesive layer onto the surface of the discontinuous indium layer, opposite the polyvinylidene difluoride-containing film.
6. A method according to claim 5, wherein the step of placing an adhesive layer onto the surface of the discontinuous indium layer comprises coating the surface of the discontinuous indium layer with an adhesive selected from the group consisting of alcohol-based adhesives and water-based adhesives.
7. A method according to claim 5, wherein the step of placing adhesive layer onto the discontinuous indium layer comprises:
depositing an acrylic adhesive layer onto a second polymeric substrate;
depositing a polyurethane adhesive layer onto the acrylic adhesive layer, opposite the second polymeric substrate;
bonding the polyurethane adhesive layer to the discontinuous indium layer; and
removing the second polymeric substrate from the acrylic adhesive layer.
8. A method according to claim 5, further comprising bonding a thermoplastic backing layer to the adhesive layer.
9. A method according to claim 8, wherein the step of bonding a thermoplastic backing layer to the adhesive layer comprises bonding a backing layer selected from the group consisting of polyvinyl chloride, thermoplastic olefins, acrylonitrile-butadiene-styrene copolymers, polycarbonates, polystyrenes, and blends of these polymers.
10. A method according to claim 1, further comprising:
removing the polymeric substrate from the polyvinylidene difluoride-containing film; and
placing an extensible polyurethane mask layer onto the surface of the polyvinylidene difluoride-containing film opposite the discontinuous indium layer.
11. A method for forming a bright metallized laminate, comprising:
applying a polyvinylidene difluoride-containing film to a polymeric substrate;
placing a polymeric film onto the polyvinylidene difluoride-containing film, opposite the polymeric substrate;
press polishing the polyvinylidene difluoride-containing film;
removing the polymeric film from the polyvinylidene difluoride-containing film after the press polishing step; and
depositing a discontinuous layer of indium islands upon the polyvinylidene difluoride-containing film.
12. A method according to claim 11, wherein the step of applying the polyvinylidene difluoride-containing film to the polymeric substrate comprises casting the film onto the polymeric substrate.
13. A method according to claim 12, wherein the step of casting a polyvinylidene difluoride-containing film onto the polymeric substrate comprises a technique selected from the group consisting of a knife-over roll coating process, a reverse roll coating process, and a slot die coating process.
14. A method according to claim 11, wherein the step of press polishing the polyvinylidene difluoride-containing film comprises pressing the polyvinylidene difluoride-containing film between a heated nip formed by rollers.
15. A method according to claim 11, further comprising placing an adhesive layer onto the surface of the discontinuous indium layer, opposite the polyvinylidene difluoride-containing film.
16. A method according to claim 15, wherein the step of placing an adhesive layer onto the surface of the discontinuous indium layer comprises coating the surface of the discontinuous indium layer with an adhesive selected from the group consisting of alcohol-based adhesives and water-based adhesives.
17. A method according to claim 15, wherein the step of placing adhesive layer onto the discontinuous indium layer comprises:
depositing an acrylic adhesive layer onto a second polymeric substrate;
depositing a polyurethane adhesive layer onto the acrylic adhesive layer, opposite the second polymeric substrate;
bonding the polyurethane adhesive layer to the discontinuous indium layer; and
removing the second polymeric substrate from the acrylic adhesive layer.
18. A method according to claim 15, further comprising bonding a thermoplastic backing layer to the adhesive layer.
19. A method according to claim 18, wherein the step of bonding a thermoplastic backing layer to the adhesive layer comprises bonding a backing layer selected from the group consisting of polyvinyl chloride, thermoplastic olefins, acrylonitrile-butadiene-styrene copolymers, polycarbonates, polystyrenes, and blends of these polymers.
20. A method according to claim 11, further comprising:
removing the polymeric substrate from the polyvinylidene difluoride-containing film; and
placing an extensible polyurethane mask layer onto the surface of the polyvinylidene difluoride-containing film, opposite the discontinuous indium layer.
21. A method for forming a bright metallized laminate, comprising depositing a discontinuous layer of indium islands upon a microscopically-smooth surface of a polyvinylidene difluoride-containing film.
22. A method for forming a bright metallized laminate according to claim 21, wherein the step of depositing a discontinuous layer of indium islands upon a microscopically-smooth surface of a polyvinylidene difluoride-containing film comprises depositing a discontinuous layer of indium islands onto a microscopically-smooth surface of a polyvinylidene difluoride-acrylic film comprising between about 30% and 90% by weight of polyvinylidene difluoride and between about 10% and 70% by weight of an acrylic polymer.
23. A method for forming a bright metallized laminate according to claim 21, wherein the step of depositing a discontinuous layer of indium islands upon a microscopically-smooth surface of a polyvinylidene difluoride-containing film comprises depositing a discontinuous layer of indium islands onto a microscopically-smooth surface of a tinted polyvinylidene difluoride-acrylic.
24. A method for forming a bright metallized laminate according to claim 21, further comprising placing an adhesive layer onto the discontinuous indium layer, opposite the polyvinylidene difluoride-containing film.
25. A method for forming a bright metallized laminate according to claim 24, wherein the step of placing an adhesive layer onto the discontinuous indium layer comprises placing a tinted adhesive layer onto the discontinuous indium layer.
26. A method for forming a bright metallized laminate according to claim 24, wherein the step of placing an adhesive layer onto the discontinuous indium layer comprises placing a composite adhesive layer onto the discontinuous indium layer.
27. A method according to claim 24, wherein the step of placing an adhesive layer on the surface of the discontinuous indium layer comprises:
depositing an acrylic adhesive layer onto a polymeric substrate;
depositing a polyurethane adhesive layer onto the acrylic adhesive layer, opposite the polymeric substrate;
bonding the polyurethane adhesive layer to the discontinuous indium layer; and
removing the polymeric substrate from the acrylic adhesive layer.
28. A method according to claim 24, wherein the step placing an adhesive layer on the surface of the discontinuous indium layer comprises coating the surface of the discontinuous indium layer with an adhesive selected from the group consisting of alcohol-based adhesives and water-based adhesives.
29. A method according to claim 24, further comprising bonding a thermoplastic backing layer to the adhesive layer.
30. A method according to claim 29, wherein the step of bonding a thermoplastic backing layer to the adhesive layer comprises bonding a backing layer selected from the group consisting of polyvinyl chloride, thermoplastic olefins, acrylonitrile-butadiene-styrene copolymers, polycarbonates, polystyrenes, and blends of these polymers.
31. A method according to claim 29, wherein the step of bonding a thermoplastic backing layer to the adhesive layer comprises bonding a tinted thermoplastic backing layer to the adhesive layer.
32. A method according to claim 21, further comprising placing an extensible polyurethane mask layer onto the surface of the polyvinylidene difluoride-containing film opposite the discontinuous indium layer.
33. A method for forming a bright metallized laminate, comprising:
applying a thermoplastic leveling layer to a polyvinylidene difluoride-containing film; and
depositing a discontinuous layer of indium islands upon the thermoplastic leveling layer.
34. A method for forming a bright metallized laminate according to claim 33, wherein the step of applying a thermoplastic leveling layer to a polyvinylidene difluoride-containing film comprises applying a thermoplastic leveling layer to a polyvinylidene difluoride-acrylic film comprising between about 30% and 90% by weight of polyvinylidene difluoride and between about 10% and 70% by weight of an acrylic polymer.
35. A method for forming a bright metallized laminate according to claim 34, wherein the step of applying a thermoplastic leveling layer to a polyvinylidene difluoride-acrylic film comprises applying a thermoplastic leveling layer to a tinted polyvinylidene difluoride-acrylic film.
36. A method for forming a bright metallized laminate according to claim 34, wherein the step of applying a thermoplastic leveling layer to a polyvinylidene difluoride-acrylic film comprises applying a tinted thermoplastic leveling layer to a polyvinylidene difluoride-acrylic film.
37. A method for forming a bright metallized laminate according to claim 34, wherein the step of applying a thermoplastic leveling layer to a polyvinylidene difluoride-acrylic film comprises applying a polyurethane thermoplastic leveling layer to a polyvinylidene difluoride-acrylic film.
38. A method according to claim 34, further comprising applying a thermoplastic primer layer to the polyvinylidene difluoride-acrylic film before the step of applying the leveling layer to the polyvinylidene difluoride-acrylic film.
39. A method according to claim 38, wherein the step applying a thermoplastic primer layer to the polyvinylidene difluoride-acrylic film comprises applying an acrylic primer layer to the polyvinylidene difluoride-acrylic film.
40. A method according to claim 34, further comprising placing an adhesive layer onto the surface of the discontinuous indium layer, opposite the thermoplastic leveling layer.
41. A method for forming a bright metallized laminate according to claim 40, wherein the step of placing an adhesive layer onto the surface of the discontinuous indium layer comprises placing a tinted adhesive layer onto the surface of the discontinuous indium layer.
42. A method for forming a bright metallized laminate according to claim 40, wherein the step of placing an adhesive layer onto the surface of the discontinuous indium layer comprises placing an adhesive layer that comprises polyurethane onto the surface of the discontinuous indium layer.
43. A method for forming a bright metallized laminate according to claim 40, wherein the step of placing an adhesive layer onto the surface of the discontinuous indium layer comprises placing an adhesive layer that comprises acrylic onto the surface of the discontinuous indium layer.
44. A method for forming a bright metallized laminate according to claim 40, wherein the step of placing an adhesive layer onto the surface of the discontinuous indium layer comprises placing a composite adhesive layer onto the surface of the discontinuous indium layer.
45. A method according to claim 40, further comprising bonding a thermoplastic backing layer to the adhesive layer.
46. A method according to claim 45 wherein the step of bonding a thermoplastic backing layer to the adhesive layer comprises bonding a backing layer selected from the group consisting of polyvinyl chloride, thermoplastic olefins, acrylonitrile-butadiene-styrene copolymers, polystyrenes, polycarbonates, and blends of these polymers.
47. A method according to claim 45, wherein the step of bonding a thermoplastic backing layer to the adhesive layer comprises bonding a tinted thermoplastic backing layer to the adhesive layer.
48. A method according to claim 34, further comprising placing an extensible polyurethane mask layer onto the surface of the polyvinylidene difluoride-acrylic film, opposite the leveling layer.