Cyclized NGR peptide compounds, compositions, and methods of their use
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-051/00
A61M-036/14
출원번호
US-0000543
(2009-06-15)
등록번호
US-8636978
(2014-01-28)
국제출원번호
PCT/US2009/047328
(2009-06-15)
§371/§102 date
20110404
(20110404)
국제공개번호
WO2010/005693
(2010-01-14)
발명자
/ 주소
Wood, Bradford J.
Dreher, Matthew
Negussie, Ayele H.
출원인 / 주소
The United States of America, as Represented by the Secretary, Department of Health and Human Services
대리인 / 주소
Woodcock Washburn LLP
인용정보
피인용 횟수 :
0인용 특허 :
10
초록
Cyclized peptide compounds containing the NGR motif of formula (I) or a pharmaceutically-acceptable salt thereof are disclosed. Compositions comprising the cyclized peptide compounds and methods of their use are also disclosed.
대표청구항▼
1. A compound of formula I (SEQ ID NO:1): or a pharmaceutically-acceptable salt thereof;wherein:R1 is (CH2)4NR12R14;R2 is hydrogen or C1-C6alkyl;R3 is CH2C(═O)NR12R15;R4 is hydrogen or C1-C6alkyl;R5 is hydrogen or C1-C6alkyl;R6 is hydrogen or C1-C6alkyl;R7 is (CH2)3NHC(NR12R14)(═N+R12R16);R8 is hydr
1. A compound of formula I (SEQ ID NO:1): or a pharmaceutically-acceptable salt thereof;wherein:R1 is (CH2)4NR12R14;R2 is hydrogen or C1-C6alkyl;R3 is CH2C(═O)NR12R15;R4 is hydrogen or C1-C6alkyl;R5 is hydrogen or C1-C6alkyl;R6 is hydrogen or C1-C6alkyl;R7 is (CH2)3NHC(NR12R14)(═N+R12R16);R8 is hydrogen or C1-C6alkyl;R9 is hydrogen or C1-C6alkyl;R10 is hydrogen or C1-C6alkyl;R11 is hydrogen or C1-C6alkyl;each R12 is, independently, hydrogen or C1-C6alkyl;R13 is hydrogen, C1-C6alkyl, or -(L)n-sm; L is a linking moiety;n is 0 or 1;sm is a support medium;R14 is hydrogen, C1-C6alkyl, amino protecting group, or a diagnostic moiety that is a fluorophore, a non-metallic isotope, an optical reporter, a boron neutron absorber, a paramagnetic metal ion, a ferromagnetic metal, a gamma-emitting radioisotope, a positron-emitting radioisotope, or an x-ray absorber;R15 is hydrogen, C1-C6alkyl, or amino protecting group; andR16 is hydrogen, C1-C6alkyl, or a guanidino-protecting group. 2. A compound of claim 1, wherein R1 is (CH2)4NH2. 3. A compound of claim 1, wherein R2 is hydrogen. 4. A compound of claim 1, wherein R3 is CH2C(═O)NH2. 5. A compound of claim 1, wherein R4 is hydrogen. 6. A compound of claim 1, wherein R5 is hydrogen. 7. A compound of claim 1, wherein R6 is hydrogen. 8. A compound of claim 1, wherein R7 is (CH2)3NHC(NH2)(═N+H2). 9. A compound of claim 1, wherein R8 is hydrogen. 10. A compound of claim 1, wherein R9 is hydrogen. 11. A compound of claim 1, wherein R10 is hydrogen. 12. A compound of claim 1, wherein R11 is hydrogen. 13. A compound of claim 1, wherein R12 is hydrogen. 14. A compound of claim 1, wherein R13 is hydrogen. 15. A compound of claim 1, herein R13 is -(L)n-sm. 16. A compound of claim 1, wherein:L is 17. A compound of claim 1, wherein n is 0. 18. A compound of claim 1, wherein n is 1. 19. A compound of claim 1, wherein R14 is hydrogen. 20. A compound of claim 1, wherein R14 is a diagnostic moiety. 21. A compound of claim 20, wherein said diagnostic moiety is a fluorophore. 22. A compound of claim 21, wherein said fluorophore is 23. A compound of claim 1, wherein R14 is an amino protecting group. 24. A compound of claim 23, wherein said amino protecting group is t-butyloxy carbonyl (BOC). 25. A compound of claim 1, wherein R15 is hydrogen. 26. A compound of claim 1, wherein R15 is an amino protecting group. 27. A compound of claim 26, wherein said amino protecting group is triphenylmethyl (trityl). 28. A compound of claim 1, wherein R16 is hydrogen. 29. A composition, comprising: a compound of claim 1 or a pharmaceutically acceptable salt thereof;a lipid-bilayer;at least one diagnostic agent that is a fluorophore, a non-metallic isotope, an optical reporter, a boron neutron absorber, a paramagnetic metal ion, a ferromagnetic metal, a gamma-emitting radioisotope, a positron-emitting radioisotope, or an x-ray absorber;or at least one therapeutic agent that is an anti-tumor agent, an anti-angiogenic agent, anti-neoplastic agent, or a combination thereof; andoptional polyethylene glycol. 30. A composition of claim 29, wherein said lipid-bilayer comprises liposomes. 31. A composition of claim 29, wherein said therapeutic agent is an anthracycline compound. 32. A composition of claim 29, wherein said compound of claim 1 or said pharmaceutically acceptable salt thereof is conjugated to said lipid bilayer. 33. A method of imaging cancerous tissue in a patient comprising: administering to said patient a composition of claim 29 comprising at least one diagnostic agent; wherein said cancerous tissue expresses aminopeptidase N isoform CD13 (APN/CD13); andperforming imaging on the patient to detect the composition bound to the cancerous tissue. 34. The compound of claim 1, wherein the guanidino-protecting group is 5-sulfonyl-2,2,4,6,7-pentamethyl-benzofuran. 35. A method of treating cancer in a patient comprising administering to said patient a composition of claim 29 comprising the least one therapeutic agent; wherein said cancerous tissue expresses aminopeptidase N isoform CD13 (APN/CD13). 36. The composition of claim 30, wherein the liposomes are sensitive at 39 degrees Celsius to 41 degrees Celsius.
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이 특허에 인용된 특허 (10)
Caruthers Marvin H. (Boulder CO) Matteucci Mark D. (San Francisco CA), Nucleosides useful in the preparation of polynucleotides.
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