Analogs of green tea polyphenols as chemotherapeutic and chemopreventive agents
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
C07D-311/02
C07D-311/00
A61K-031/352
출원번호
US-0731690
(2003-12-08)
발명자
/ 주소
Zaveri,Nurulain
Chao,Wan Ru
Bensari,Ahlem
출원인 / 주소
SRI International
대리인 / 주소
Mintz, Levin, Cohn, Ferris, Glovsky and Popeo, P.C.
인용정보
피인용 횟수 :
4인용 특허 :
3
초록▼
Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of polyphenol catechins that occur in green tea, such as epigallocatichin-3-gallate (EGCG), and have the structure of formula (I) wherein R1 through R11 are defined herein. Preferred R4 m
Novel compounds useful as chemotherapeutic and chemopreventive agents are provided. The compounds are analogs of polyphenol catechins that occur in green tea, such as epigallocatichin-3-gallate (EGCG), and have the structure of formula (I) wherein R1 through R11 are defined herein. Preferred R4 moieties are selected from O, S, NH and CH2, and in exemplary compounds, R4 is O and R5 is a tri-substituted aroyloxy substituent, such as a 3,4,5-substituted benzoyloxy group. Pharmaceutical compositions are provided as well, as are methods of chemotherapy and chemoprevention.
대표청구항▼
What is claimed is: 1. A compound having the structural formula (I) wherein: R1, R2 and R3 are selected from the group consisting of hydroxyl, alkyl, halo, sulfhydryl, alkoxy, and aryloxy; R4 is O; R5 is selected from the group consisting of SH, acyloxy, and N(Rx)2 wherein the Rx may be the same
What is claimed is: 1. A compound having the structural formula (I) wherein: R1, R2 and R3 are selected from the group consisting of hydroxyl, alkyl, halo, sulfhydryl, alkoxy, and aryloxy; R4 is O; R5 is selected from the group consisting of SH, acyloxy, and N(Rx)2 wherein the Rx may be the same or different and are hydrogen or alkyl; R6 and R8 are independently selected from the group consisting of hydroxyl, alkyl, alkoxy, and aryloxy; R7 and R9 are independently selected from the group consisting of hydrogen, hydroxyl, alkyl, alkoxy, and aryloxy; and R10 and R11 are independently selected from the group consisting of hydrogen, hydroxyl, alkyl, alkoxy, and halo, with the proviso that when (a) R7, R9, R 10, and R11 are hydrogen, and (b) R1, R2, R3, R6, and R8 are hydroxyl, then (c) R5 is other than 3,4,5-trihydroxybenzoyloxy or 3,4,5-trimethoxybenzoyloxy. 2. The compound of claim 1, wherein R1, R2 and R3 are selected from the group consisting of hydroxyl, C 1-C6 alkyl, halo, C1-C6 alkoxy, and C 5-C12 aryloxy; R5 is selected from the group consisting of C 6-C32 acyloxy and NH2; R6 and R8 are independently selected from the group consisting of hydroxyl, C1-C6 alkyl, C 1-C6 alkoxy, and C5-C12 aryloxy; R7 and R9 are independently selected from the group consisting of hydrogen, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, and C5-C12 aryloxy; and R10 and R11 are independently selected from the group consisting of hydrogen, hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, and halo. 3. The compound of claim 2, wherein R7, R9, R10 and R11 are hydrogen. 4. The compound of claim 3, in enantiomerically pure form in the 2β,3β-cis, 2α,3α-cis, 2α,3β-trans, or 2β,3α-trans configuration. 5. The compound of claim 3, comprising a racemic mixture of the 2α,3β-trans and 2β,3α-trans enantiomers. 6. The compound of claim 3, comprising a racemic mixture of the 2α,3α-cis and 2β,3β-cis enantiomers. 7. The compound of claim 3, wherein: R5 is an acyloxy substituent having the structure in which R12, R13, and R14 are independently selected from the group consisting of hydrogen, hydroxyl, alkyl, alkoxy, and aryloxy. 8. The compound of claim 7, wherein: R12, R13, and R14 are selected from the groups consisting of hydroxyl, C1-C6 alkyl, C1-C6 alkoxy, and C5-C12 aryloxy. 9. The compound of claim 8, wherein: R12, R13, and R14 are independently selected from the group consisting of hydroxyl, methyl, and methoxy, and benzyloxy. 10. A compound having the structural formula (II) wherein: R1, R2, and R3 are selected from the group consisting of hydroxyl, alkyl, halo, sulfhydryl, alkoxy, and aryloxy; and R6 and R8 are selected from the group consisting of alkyl, alkoxy, and aryloxy, wherein R1, R2 , R3, R6 and R8 are not all the same. 11. The compound of claim 10, wherein R1, R2 and R3 are selected from the group consisting of hydroxyl, C1-C6 alkyl, halo, C1-C6 alkoxy, and C5-C12 aryloxy; and R6 and R8 are selected from the group consisting of C1-C6 alkyl, C1-C6 alkoxy, and C5-C12 aryloxy. 12. The compound of claim 11, wherein R1, R2 , and R3 are independently selected from hydroxyl, methyl, and methoxy; and R6 and R8 are independently selected from hydroxyl, methyl, and methoxy. 13. An analog of (-)-epigallocatechin-3-gallate (EGCG), wherein the analog contains at least one modification relative to ECGC that results in an IC50 of less than 60 when the analog is evaluated for its ability to inhibit growth in a breast cancer cell line using MTT assay. 14. The analog of claim 13, wherein the analog contains at least one modification relative to ECGC that results in an IC50 of less than 25 when the analog is evaluated for its ability to inhibit growth in a breast cancer cell line using MTT assay. 15. The analog of claim 14, wherein the analog contains at least one modification relative to ECGC that results in an IC50 of less than 15 when the analog is evaluated for its ability to inhibit growth in a breast cancer cell line using MTT assay. 16. A compound having the structural formula selected from 17. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 1 in combination with a pharmaceutically acceptable carrier. 18. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 2 in combination with a pharmaceutically acceptable carrier. 19. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 3 in combination with a pharmaceutically acceptable carrier. 20. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 4 in combination with a pharmaceutically acceptable carrier. 21. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 5 in combination with a pharmaceutically acceptable carrier. 22. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 7 in combination with a pharmaceutically acceptable carrier. 23. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 8 in combination with a pharmaceutically acceptable carrier. 24. A pharmaceutical composition comprising a therapeutically effective amount of the compound of claim 14 in combination with a pharmaceutically acceptable carrier. 25. The composition of any one of claims 17 through 24, wherein the pharmaceutically acceptable carrier is suitable for oral administration and the composition comprises an oral dosage form. 26. The composition of claim 25, wherein the oral dosage form is a tablet. 27. The composition of claim 25, wherein the oral dosage form is a capsule. 28. The composition of any one of claims 17 through 24, wherein the pharmaceutically acceptable carrier is suitable for parenteral administration and the composition comprises a parenterally administrable formulation.
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이 특허에 인용된 특허 (3)
Albert Alban (Avully CHX) Courbat Pierre (Nyon CHX) Weith Andr (Prangins CHX), 3-O-acylated derivatives of (+)-cyanidan-3-ol.
Burdick,David Carl; Egger,Heinz; Gum,Andrew George; Koschinski,Ingo; Muelchi,Elena; Prevot Halter,Isabelle, Process for the production of (-)-epigallocatechin gallate.
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