Carbidopa prodrugs and derivatives, and compositions and uses thereof
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-031/216
A61K-031/21
C07C-229/28
C07C-229/00
출원번호
US-0728942
(2003-12-08)
발명자
/ 주소
Xiang,Jia Ning
Gallop,Mark A.
Cundy,Kenneth C.
Li,Jianhua
Xu,Feng
Zhou,Cindy X.
Bhat,Laxminarayan
출원인 / 주소
XenoPort, Inc.
대리인 / 주소
Finnegan, Henderson, Farabow, Garrett &
인용정보
피인용 횟수 :
67인용 특허 :
36
초록
Prodrugs of carbidopa, derivatives of carbidopa prodrugs, methods of making prodrugs of carbidopa and derivatives thereof, methods of using prodrugs of carbidopa and derivatives thereof, and compositions of prodrugs of carbidopa and derivatives thereof are disclosed.
대표청구항▼
What is claimed is: 1. A compound of Formula (I): a stereoisomer thereof, an enantiomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate of any of the foregoing, wherein: X is a moiety of Formula (II): where: R1 is selected from hydrogen and a moiety compr
What is claimed is: 1. A compound of Formula (I): a stereoisomer thereof, an enantiomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate of any of the foregoing, wherein: X is a moiety of Formula (II): where: R1 is selected from hydrogen and a moiety comprising Formula (IX): R4 and R5 are independently selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroalkyl, substituted heteroalkyl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl,--C(O)OR27,--C(O)R27,--(CR 16R17)OC(O)R11 and moieties of Formulae (XVII) and (XVIII): wherein o is 1-3, and the cycloheteroalkyl rings in (XVII) and (XVIII) are optionally substituted with one or more groups selected from halo, CN, NO2, OH, C1-6 alkyl, and C1-6 alkoxy; or R4 and R5 together form a structure selected from Formulae (XII) to (XVI): wherein the aryl ring in Formula (XV) is optionally substituted with one or more groups selected from halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, and--CO2R31; R11 is selected from hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl, substituted heteroalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl, or optionally, R11 and either R16 or R17, together with the atoms to which R11, and either R16 or R17 are attached, form a cycloheteroalkyl or substituted cycloheteroalkyl ring, optionally to which is fused an aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl or substituted cycloheteroalkyl ring; R16 and R17 are independently selected from hydrogen, alkyl, substituted alkyl, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, carbamoyl, substituted carbomoyl, cycloalkyl, substituted cycloalkyl, cycloalkoxycarbonyl, substituted cycloalkoxycarbonyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl or optionally, R16 and R17 together with the carbon atom to which R16 and R17 are attached form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl or substituted cycloheteroalkyl ring; R27 is selected from alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; R28 and R29 are independently selected from hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroalkyl, and substituted heteroalkyl; and R31is selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; with the proviso that none of R1, R4, R5, R11, R16, R17, R27, R28, R29, and R31 comprise a bile acid moiety. 2. A compound of Formula (Ib): a stereoisomer thereof, an enantiomer thereof, a pharmaceutically acceptable salt thereof, a hydrate thereof, or a solvate of any of the foregoing, wherein: R1 is selected from hydrogen, and a moiety comprising Formula (IX): R4 and R5 are independently selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heteroalkyl, substituted heteroalkyl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, substituted heteroarylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl,--C(O)OR27,--C(O)R27,--(CR 16R17)OC(O)R11 and moieties of Formulae (XVII) and (XVIII): wherein o is 1-3, and the cycloheteroalkyl rings in (XVII) and (XVIII) are optionally substituted with one or more groups selected from halo, CN, NO2, OH, C1-6 alkyl, and C1-6 alkoxy; or R4 and R5 together form a structure selected from Formulae (XII) to (XVI): wherein the aryl ring in Formula (XV) is optionally substituted with one or more groups selected from halo, CN, OH, C1-6 alkyl, C1-6 alkoxy, and--CO2R31; R11 is selected from hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, heteroalkyl, substituted heteroalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl, or optionally, R11 and either R16 or R17, together with the atoms to which R11, R16 and R17 are attached, form a cycloheteroalkyl or substituted cycloheteroalkyl ring, to which an aryl, substituted aryl, heteroaryl, substituted heteroaryl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl or substituted cycloheteroalkyl ring is optionally fused to said cycloheteroalkyl or substituted cycloheteroalkyl ring; R16 and R17 are independently selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, heteroarylalkyl, and substituted heteroarylalkyl or optionally, R16 and R17 together with the carbon atoms to which R16 and R17 are attached form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl or substituted cycloheteroalkyl ring; R27 is selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; R28 and R29 are independently selected from hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, alkoxycarbonyl, substituted alkoxycarbonyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, heteroalkyl, and substituted heteroalkyl; and R31is selected from hydrogen, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, cycloheteroalkyl, substituted cycloheteroalkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl, and substituted heteroarylalkyl; with the proviso that none of R1, R4, R5, R11, R16, R17, R 27, R28, R29, and R31 comprise a bile acid moiety. 3. A compound according to claim 2, wherein R4 and R5 are independently selected moieties from Formulae (XVII), and (XVIII). 4. A compound according to claim 2, wherein R1 hydrogen. 5. A compound according to claim 2, wherein R1 a moiety comprising Formula (IX). 6. A compound according to claim 2, wherein R4 and R5 are independently selected from hydrogen, alkanyl, substituted alkanyl, arylalkanyl, substituted arylalkanyl, heteroarylalkanyl, substituted heteroarylalkanyl, cycloalkanyl, substituted cycloalkanyl, cycloheteroalkanyl, and substituted cycloheteroalkanyl. 7. A compound according to claim 2, wherein R4 and R5 are independently selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, cyclopentyl, cyclohexyl, benzyl, and pyridyl, where the aryl rings of the benzyl and pyridyl groups are optionally substituted with one or more substituents selected from halo, CN, NO2, OH, C1-6 alkyl, C1-6 alkoxy and--CO2R31. 8. A compound according to claim 2, wherein R4 and R5 are independently selected from hydrogen,--C(O)OR27, and--C(O)R27. 9. A compound according to claim 8, wherein R27 is selected from C1-10 alkyl, substituted C1-10 alkyl, C5-8 aryl, C5-8 substituted aryl, C6-10 arylalkyl, and substituted C6-10 arylalkyl. 10. A compound according to claim 2, wherein R4 and R5 are both independently--C(O)OR27 or--C(O)R 27. 11. A compound according to claim 10, wherein R27 is selected from C1-10 alkyl, substituted C1-10 alkyl, C5-8 aryl, C5-8 substituted aryl, C6-10 arylalkyl, and substituted C6-10 arylalkyl. 12. A compound according to claim 2, wherein R27 is an alkyl selected from alkanyl, substituted alkanyl, cycloalkanyl, substituted cycloalkanyl, arylalkanyl, substituted arylalkanyl, heteroarylalkanyl, and substituted heteroarylalkanyl. 13. A compound according to claim 2, wherein R27 is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and benzyl, where the aryl ring of the benzyl group is optionally substituted with one or more substituents selected from halo, CN, NO2, OH, C1-6 alkyl, C1-6 alkoxy, and--CO2R31. 14. A compound according to claim 2, wherein R27 is selected from aryl, substituted aryl, heteroaryl, and substituted heteroaryl. 15. A compound according to claim 2, wherein R27 is selected from phenyl, pyridyl, furyl, and thienyl, the aromatic rings of which are optionally substituted with one or more substituents selected from halo, CN, NO2, OH, C1-6 alkyl, C1-6 alkoxy, and--CO2R31. 16. A compound according to claim 2, wherein R4 and R5 are independently selected from hydrogen and--(CR16 R17)OC(O)R11. 17. A compound according to claim 16, wherein R11 is selected from hydrogen, C1-10 alkyl, substituted C1-10 alkyl, C5-8 aryl, substituted C5-8 aryl, C1-15 alkoxy, and substituted C1-15 alkoxy. 18. A compound according to claim 16, wherein R16 and R17 are independently selected from hydrogen, C1-16 alkyl, substituted C1-16 alkyl, C5-8 aryl, substituted C5-8 aryl, C6-10 arylalkyl, and substituted C6-10 arylalkyl. 19. A compound according to claim 2, wherein R4 and R5 are both independently--(CR16R17)OC(O)R 11. 20. A compound according to claim 19, wherein R11 is selected from hydrogen, C1-10 alkyl, substituted C1-10 alkyl, C5-8 aryl, substituted C5-8 aryl, C1-15 alkoxy, and substituted C1-15 alkoxy. 21. A compound according to claim 19, wherein R16 and R17 are independently selected from hydrogen, C1-16 alkyl, substituted C1-16 alkyl, C5-8 aryl, substituted C5-8 aryl, C6-10 arylalkyl, and substituted C6-10 arylalkyl. 22. A compound according to claim 2, wherein R11 is an alkyl selected from alkanyl, substituted alkanyl, alkenyl, substituted alkenyl, arylalkanyl, substituted arylalkanyl, arylalkenyl, substituted arylalkenyl, cycloalkanyl, substituted cycloalkanyl, cycloheteroalkanyl, substituted cycloheteroalkanyl, heteroarylalkanyl, and substituted heteroarylalkanyl. 23. A compound according to claim 2,wherein R11 is selected from methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, hexyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and styryl, where the aryl ring of the styryl group is optionally substituted with one or more substituents are selected from halo, CN, NO2, OH, C1-6 alkyl, C1-6 alkoxy, and--CO2R31. 24. A compound according to claim 2, wherein R11 is selected from aryl, substituted aryl, heteroaryl, and substituted heteroaryl. 25. A compound according to claim 2, wherein R11 is selected from phenyl, pyridyl, indolyl, furyl, imidazolyl, and oxazolyl, the aromatic rings of which are optionally substituted with one or more substituents selected from halo, CN, NO2, OH, C1-6 alkyl, C1-6 alkoxy, and--CO2R31. 26. A compound according to claim 2, wherein R11 is selected from hydrogen, C1-10 alkyl, substituted C1-10 alkyl, C5-8 aryl, substituted C5-8 aryl, C1-15 alkoxy, and substituted C1-15 alkoxy. 27. A compound according to claim 2, wherein R11 is selected from methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy, tert-butoxy, pentyloxy, hexyloxy, cyclopropoxy, cyclobutoxy, cyclopentyloxy, cyclohexyloxy, 2,6-dimethylcyclohexyloxy, fenchyloxy, and adamantyloxy. 28. A compound according to claim 2, wherein R11 and either R16 or R17, together with the atoms to which R11 and either R16 or R17 are attached, form a cycloalkyl, substituted cycloalkyl, cycloheteroalkyl or substituted cycloheteroalkyl ring, to which an aryl, substituted aryl, heteroaryl or substituted heteroaryl ring is optionally fused to said cycloheteroalkyl or substituted cycloheteroalkyl ring. 29. A compound according to claim 2, wherein R1 is hydrogen, R4 and R5 are each C(O)OR27, R16 is hydrogen, R27 is ethyl, R11 is selected from C1-4 alkyl, C1-4 alkoxy, cyclohexyloxy, 2,6-dimethylcyclohexyloxy, fenchyloxy, and adamantyloxy, and R17 is selected from hydrogen, and C1-4 alkyl. 30. A compound according to claim 29, wherein R17 is hydrogen. 31. A compound according to claim 29, wherein R17 is methyl. 32. A compound according to claim 2, wherein R1 is hydrogen, R4 and R5 are each C(O)R27, R16 is hydrogen, R27 is isopropyl, R11 is selected from C1-4 alkyl, C1-4 alkoxy, cyclohexyloxy, 2,6-dimethylcyclohexyloxy, fenchyloxy, and adamantyloxy, and R17 selected from hydrogen, and C1-4 alkyl. 33. A compound according to claim 32, wherein R17 is hydrogen. 34. A compound according to claim 32, wherein R17 is methyl. 35. A compound according to claim 2, wherein R1 is hydrogen, R4 and R5 are each C(O)R27, R16 is hydrogen, R27 is tert-butyl, R11 is selected from C1-4 alkyl, C1-4 alkoxy, cyclohexyloxy, 2,6-dimethylcyclohexyloxy, fenchyloxy, and adamantyloxy, and R17 is selected from hydrogen, and C1-4 alkyl. 36. A compound according to claim 35, wherein R17 is hydrogen. 37. A compound according to claim 35, wherein R17 is methyl. 38. A compound according to claim 2, wherein R16 and R17 are independently selected from hydrogen, alkanyl, substituted alkanyl, cycloalkanyl, substituted cycloalkanyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, arylalkanyl, and substituted arylalkanyl. 39. A compound according to claim 2, wherein R16 and R17 are independently selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, and benzyl. 40. A compound according to claim 2, wherein R16 is hydrogen and R17 is selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, phenyl, and benzyl. 41. A compound according to claim 2, wherein R16 and R17 together with the carbon atoms to which R16 and R17 are attached form a cycloalkanyl, substituted cycloalkanyl, cycloheteroalkanyl or substituted cycloheteroalkanyl ring. 42. A compound according to claim 2, wherein R16 and R17 together with the carbon atoms to which R16 and R17 are attached form a cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl ring. 43. A compound according to claim 2, wherein R16 and R17 are independently selected from hydrogen, C1-16 alkyl, substituted C1-16 alkyl, C5-8 aryl, substituted C5-8 aryl, C6-10 arylalkyl, and substituted C6-10 arylalkyl. 44. A compound according to claim 2, wherein R28 and R29 are independently selected from hydrogen, alkanyl, aryl, and alkoxycarbonyl. 45. A compound according to claim 2, wherein R28 and R29 are independently selected from hydrogen, methyl, ethyl, propyl, butyl, phenyl, methoxycarbonyl, and ethoxycarbonyl. 46. A compound according to claim 2, wherein R28 and R29 are both hydrogen. 47. A compound according to claim 2, wherein R31 is selected from hydrogen and C1-8 alkyl. 48. A compound according to claim 2, wherein R31 is selected from hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. 49. A pharmaceutical composition comprising at least one pharmaceutically acceptable excipient, and a therapeutically effective amount of at least one compound according to any one of claims 1 or 48. 50. The pharmaceutical composition of claim 49, wherein the pharmaceutical composition further comprises at least one additional active agent. 51. The pharmaceutical composition of claim 50, wherein the at least one additional active agent is susceptible to decarboxylation, and the amount of the at least one compound is in an effective amount to inhibit decarboxylation of the at least one additional active agent. 52. The pharmaceutical composition of claim 50, wherein the at least one additional active agent is selected from levodopa and prodrugs of levodopa. 53. The pharmaceutical composition of claim 49, wherein the pharmaceutical composition is formulated for oral administration. 54. The pharmaceutical composition of claim 53, wherein the pharmaceutical composition is a sustained release formulation. 55. The pharmaceutical composition of claim 50, wherein the compound and the additional active agent comprise a single unit dosage form. 56. The pharmaceutical composition of claim 49, wherein the at least one compound is present in an amount effective for the treatment in a patient of a disease selected from Parkinson's disease, and hypertension. 57. A method of treating a Parkinson's disease in a patient, in need of such treatment, comprising administering to the patient a therapeutically effective amount of an active agent that is susceptible to decarboxylation, and at least one compound according to any of claims 1 or 2. 58. The method of claim 57, wherein the active agent is selected from levodopa and prodrugs of levodopa. 59. A method of treating hypertension in a patient in need of such treatment comprising administering to the patient a therapeutically effective amount of at least one compound according to any of claims 1 or 2. 60. A method of providing a therapeutically effective concentration of at least one active agent selected from levodopa and prodrugs of levodopa in the plasma of a patient, which active agent is susceptible to premature inactivation by decarboxylation, comprising co-administering to the patient the at least one active agent and the at least one compound according to any one of claims 1 or 2. 61. A method of inhibiting decarboxylation of at least one active agent selected from levodopa and prodrugs of levodopa in a patient, comprising administering to the patient at least one compound according to any one of claims 1 or 2. 62. The method of claim 61, wherein inhibiting decarboxylation comprises inhibiting a decarboxylase enzyme. 63. The compound of claim 1, wherein the compound is selected from: (S)-3-(3,4-Dihydroxy)phenyl-2-hydrazino-2-methylpropionic acid (1R)-cyclohexyloxycaxbonyloxyethyl ester; (S)-3-(3,4-Dihydroxy)phenyl-2-hydrazino-2-methylpropionic acid (1S)-cyclohexyloxycarbonyloxyethyl ester; (S)-3-(3,4-Dihydroxyphenyl)-2-hydrazino-2-methyl-propionic acid acetoxymethyl ester; (S)-3-(3,4-Dihydroxy-phenyl)-2-hydrazino-2-methyl-propionic acid 2,2-dimethyl-propionyloxymethyl ester; (S)-3-(3,4-Bis-ethoxycarbonyloxy-phenyl)-2-hydrazino-2-methylpropionic acid 2,2-dimethyl-propionyloxymethyl ester; (S)-3-(3,4-Dihydroxy-phenyl)-2-hydrazino-2-methyl-propionic acid 3-oxo-1,3-dihydro-isobenzofuran-1-yl ester; (S)-3-(3,4-Bis-isobutyryloxy)phenyl-2-hydrazino-2-methylpropionic acid acetoxymethyl ester; (S)-3-(3,4-Bis-isobutyryloxy)phenyl-2-hydrazino-2-methylpropionic acid 2,2-dimethyl-propionyloxymethyl ester; (S)-3-(3,4-Bis-propionyloxy)phenyl-2-hydrazino-2-methylpropionic acid acetoxymethyl ester; (S)-3-[3,4-Bis-(2,2-dimethylpropionyloxy)phenyl]-2-hydrazino-2-methylpropionic acid acetoxymethyl ester; (S)-3-[3,4-Bis-(2,2-dimethylpropionyloxy)phenyl]-2-hydrazino-2-methylpropionic acid 2,2-dimethylpropionyloxymethyl ester; (S)-3-(3,4-Bis-ethoxycarbonyloxy)phenyl-2-hydrazino-2-methylpropionic acid (1R)-isobutyryloxy-2-methylpropyl ester; (S)-3-(3,4-Bis-ethoxycarbonyloxy)phenyl-2-hydrazino-2-methylpropionic acid (1S)-isobutyryloxy-2-methylpropyl ester; (S)-3-(3,4-Bis-ethoxycarbonyloxy)phenyl-2-hydrazino-2-methylpropionic acid (1R)-acetoxy-2-methylpropyl ester; (S)-3-(3,4-Bis-ethoxycarbonyloxy)pheny1-2-hydrazino-2-methylpropionic acid (1S)-acetoxy-2-methylpropyl ester; (S)-3-(3,4-Bis-ethoxycarbonyloxy)phenyl-2-hydrazino-2-methylpropionic acid 1(R)-isobutyryloxyethyl ester; (S)-3-(3,4-Bis-ethoxycarbonyloxy)phenyl-2-hydrazino-2-methylpropionic acid 1(S)-isobutyryloxyethyl ester; (S)-3-(3,4-Bis-ethoxycarbonyloxy)phenyl-2-hydrazino-2-methylpropionic acid isobutyryloxymethyl ester; (S)-3-(3,4-Dihydroxy)phenyl-2-hydrazino-2-methylpropionic acid 2-methylbenzoyloxymethyl ester; (S)-3-(3,4-Dihydroxy)phenyl-2-hydrazino-2-methylpropionic acid 2,6-dimethylbenzoyloxymethyl ester; (S)-3-(3,4-Dihydroxy)phenyl-2-hydrazino-2-methylpropionic acid ethoxycarbonyloxymethyl ester; (S)-3-(3,4-Bis-ethoxycarbonyloxy)phenyl-2-hydrazino-2-methylpropionic acid ethoxycarbonyloxymethyl ester; (S)-3-(3,4-Diacetoxy)phenyl-2-hydrazino-2-methylpropionic acid ethoxycarbonyloxymethyl ester; (S)-3-(3,4-Bis-isobutyryloxy)phenyl-2-hydrazino-2-methylpropionic acid ethoxycarbonyloxymethyl ester; (S)-3-(3,4-Bis-isobutyryloxy)phenyl-2-hydrazino-2-methylpropionic acid (1R)-ethoxycarbonyloxyethyl ester; (S)-3-(3,4-Bis-isobutyryloxy)phenyl-2-hydrazino-2-methylpropionic acid (1S)-ethoxycarbonyloxyethyl ester; (S)-3-(3,4-Bis-ethoxycarbonyl)oxyphenyl-2-hydrazino-2-methylpropionic acid (1R)-ethoxycarbonyloxyethyl ester; (S)-3-(3,4-Bis-ethoxycarbonyl)oxyphenyl-2-hydrazino-2-methylpropionic acid (1S)-ethoxycarbonyloxyethyl ester; (S)-3-(3,4-Dihydroxy)phenyl-2-hydrazino-2-methylpropionic acid (1R)-ethoxycarbonyloxyethyl ester; (S)-3-(3,4-Dihydroxy)phenyl-2-hydrazino-2-methylpropionic acid (1S)-ethoxycarbonyloxyethyl ester; (S)-3-(3,4-Dihydroxy)phenyl-2-hydrazino-2-methylpropionic acid (1R)-isopropoxycarbonyloxyethyl ester; (S)-3-(3,4-Dihydroxy)phenyl-2-hydrazino-2-methylpropionic acid (1S)-isopropoxycarbonyloxyethyl ester; (S)-3-(3,4-Bis-isobutyryloxy)phenyl-2-hydrazino-2-methylpropionic acid (1R)-isopropoxycarbonyloxyethyl ester; (S)-3-(3,4-Bis-isobutyryloxy)phenyl-2-hydrazino-2-methylpropionic acid (1S)-isopropoxycarbonyloxyethyl ester; (S)-3-(3,4-Dihydroxy)phenyl-2-hydrazino-2-methylpropionic acid (1R)-{[(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yloxy)carbonyl]oxy} ethyl ester; and (S)-3-(3,4-Dihydroxy)phenyl-2-hydrazino-2-methylpropionic acid (1S)-{[(1,3,3-trimethyl-bicyclo[2.2.1]hept-2-yloxy)carbonyl]oxy} ethyl ester; or pharmaceutically acceptable salts thereof, or solvates of any of the foregoing.
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