Ecteinascidin analogs for use as antitumour agents
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A01N-043/58
A01N-043/60
A61K-031/50
A61K-031/495
C07D-487/00
C07D-491/00
C07D-513/00
출원번호
UP-0485536
(2002-08-06)
등록번호
US-7763615
(2010-08-13)
우선권정보
GB-0119243.4(2001-08-07)
국제출원번호
PCT/GB2002/003592
(2002-08-06)
§371/§102 date
20050518
(20050518)
국제공개번호
WO03/014127
(2003-02-20)
발명자
/ 주소
Gallego, Pilar
Cuevas, Carmen
Munt, Simon
Manzanares, Ignacio
Martinez, Valentin
출원인 / 주소
Pharma Mar, S.A.
대리인 / 주소
Sonnenfeld, Kenneth H.
인용정보
피인용 횟수 :
1인용 특허 :
13
초록▼
Derivatives of ecteinascidin 736 of general formula (I) wherein the groups R1, R2, R3, R4 and R5 are each independently selected from the group consisting of H, OH, OR′, SH, SR′, SOR′, SO2R′, C(═O)R′, C(═O)OR′, NO2, NH2, NHR′, N(R′
Derivatives of ecteinascidin 736 of general formula (I) wherein the groups R1, R2, R3, R4 and R5 are each independently selected from the group consisting of H, OH, OR′, SH, SR′, SOR′, SO2R′, C(═O)R′, C(═O)OR′, NO2, NH2, NHR′, N(R′)2, NHC(O)R′, CN, halogen, ═O, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclic; wherein X is independently selected of OR′, CN, (═O), or H; wherein each of the R′ groups is independently selected from the group consisting of H, OH, NO2, NH2, SH, CN, halogen, ═O, C(═O)H, C(═O)CH3, CO2H, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted aryl; wherein m is 0, 1 or 2; and wherein n is 0, 1, 2, 3, or 4, and their use as antitumoral agent.
대표청구항▼
The invention claimed is: 1. A compound of the general formula I: wherein R1 is OH, OR′, SH, SR′, SOR′, SO2R′, NO2, NH2, NHR′, N(R′)2, NHC(═O)R′, CN, halogen, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 al
The invention claimed is: 1. A compound of the general formula I: wherein R1 is OH, OR′, SH, SR′, SOR′, SO2R′, NO2, NH2, NHR′, N(R′)2, NHC(═O)R′, CN, halogen, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted carbocyclic aryl selected from phenyl, naphthyl, biphenyl, phenanthryl and anthracyl, substituted or unsubstituted heterocyclic selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholinyl and pyrrolidinyl; R2, R3, R4, and R5 are each independently selected from H, OH, OR′, SH, SR′, SOR′, SO2R′, C(═O)R′, C(═O)OR′, NO2, NH2, NHR′, N(R′)2, NHC(═O)R′, CN, halogen, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, substituted or unsubstituted carbocyclic aryl selected from phenyl, naphthyl, biphenyl, phenanthryl and anthracyl, and substituted or unsubstituted heterocyclic selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholinyl and pyrrolidinyl; wherein X is independently selected from OR′, CN, (═O), and H; wherein each of the R′ groups is independently selected from the group consisting of H, OH, NO2, NH2, SH, CN, halogen, ═O, C(═O)H, C(═O)CH3, CO2H, substituted or unsubstituted C1-C25 alkyl, substituted or unsubstituted C2-C18 alkenyl, substituted or unsubstituted C2-C18 alkynyl, and substituted or unsubstituted carbocyclic aryl selected from phenyl, naphthyl, biphenyl, phenanthryl and anthracyl; wherein m is 0, 1 or 2; and wherein n is 1, 2, 3 or 4. 2. A compound according to claim 1, wherein: R1 is hydroxy, halogen, alkyl, alkoxy or aralkyl; R2 and R3 are each independently selected from hydrogen, C(═O)R′, COOR′, and optionally substituted alkyl and optionally substituted alkenyl, wherein R′ is optionally substituted alkyl or optionally substituted alkenyl and wherein the optional substituents being chosen from halo, amino, amino derived from amino acid, carbocyclic aryl selected from phenyl, naphthyl, biphenyl, phenanthryl and anthracyl, or heterocyclic selected from coumarinyl, quinolinyl, pyridyl, pyrazinyl, pyrimidyl, furyl, pyrrolyl, thienyl, thiazolyl, oxazolyl, imidazolyl, indolyl, benzofuranyl, benzothiazolyl, tetrahydrofuranyl, tetrahydropyranyl, piperidinyl, morpholinyl and pyrrolindinyl; R4 is hydrogen, alkyl, alkenyl or C(═O)OR′, where R′ is alkenyl; R5 is hydrogen or alkyl; X is hydrogen, hydroxy, cyano or (═O); m is 0 or 1; and n is 1. 3. A compound according to claim 1, wherein R1 is hydroxy, fluorine, methyl, methoxy or benzyloxy, and n is 1. 4. A compound according to claim 1, wherein R2 is hydrogen, acetyl, trifluoromethylcarbonyl, heptafluorobutyryl, 3-chloropropionyl, cinnamoyl, t-butyl-O—CO—, allyl-O—CO— or vinyl-O—CO. 5. A compound according to claim 1 wherein R3 is hydrogen, allyl, CH3—(CH2)n—CO— where n is 1, 2, 4, 6, 12, 14 or 16; t-butyl-O—CO—, allyl-O—CO— or vinyl-O—CO. 6. A compound according to claim 1 wherein R4 is hydrogen, C1 to C3 alkyl, allyl, or vinyl-O—CO. 7. A compound according to claim 1 wherein R5 is hydrogen or methyl and m is 1. 8. A compound according to claim 1, wherein X is hydroxy. 9. A compound according to claim 1 wherein R2 is not acetyl. 10. A compound according to claim 1 wherein R3 is not hydrogen. 11. A compound according to claim 1 wherein R5 is not hydrogen. 12. A pharmaceutical composition which comprises a compound according to claim 1 together with a pharmaceutically acceptable diluent. 13. A method for the treatment of lung cancer, colon cancer, kidney cancer, prostate cancer, cervical cancer, ovarian cancer, breast cancer, pancreatic cancer, leukaemia or melanoma in a mammal, comprising administering to a mammal in need of such treatment an effective amount of a compound of general formula according to claim 1. 14. A compound according to claim 2, wherein R1 is hydroxy, fluorine, methyl, methoxy or benzyloxy, and n is 1. 15. A compound according to claim 2 wherein R2 is hydrogen, acetyl, trifluoromethylcarbonyl, heptafluorobutyryl, 3-chloropropionyl, cinnamoyl, t-butyl-O—CO—, allyl-O—CO— or vinyl-O—CO. 16. A compound according to claim 2 wherein R3 is hydrogen, allyl, CH3—(CH2)n—CO— where n is 1, 2, 4, 6, 12, 14 or 16, t-butyl-O—CO—, allyl-O—CO— or vinyl-O—CO—. 17. A compound according to claim 2 wherein R4 is hydrogen, C1 to C3 alkyl, allyl or vinyl-O—CO—. 18. A compound according to claim 2 wherein R5 is hydrogen or methyl and m is 1. 19. A compound according to claim 2 wherein X is hydroxy. 20. A compound according to claim 2 wherein X is cyano. 21. A compound according to claim 1 wherein X is cyano. 22. A compound according to claim 1 of formula: 23. A compound according to claim 1 of formula: 24. A compound according to claim 1 of formula: 25. A compound according to claim 1 of formula: 26. A compound according to claim 1 of formula: 27. A compound according to claim 1 of formula: 28. A compound according to claim 1 of formula: 29. A compound according to claim 1 of formula: 30. A compound according to claim 1 of formula: 31. A pharmaceutical composition which comprises a compound according to claim 2 together with a pharmaceutically acceptable diluent. 32. A method for the treatment of lung cancer, colon cancer, kidney cancer, prostate cancer, cervical cancer, ovarian cancer, breast cancer, pancreatic cancer, leukaemia or melanoma in a mammal, comprising administering to a mammal in need of such treatment an effective amount of a compound of general formula according to claim 2.
연구과제 타임라인
LOADING...
LOADING...
LOADING...
LOADING...
LOADING...
이 특허에 인용된 특허 (13)
Rinehart Kenneth (Urbana IL) Ryuichi Sakai (Urbana IL) Holt Tom G. (Westfield NJ), Compositions comprising ecteinascidins and a method of treating herpes simplex virus infections therewith.
Rinehart Kenneth L. ; Morales Jose J. ; Reid Joel ; Reymundo Isabel,ESX ; Floriano Pablo,ESX ; Gravalos Lola Garcia,ESX, ETM-775 metabolite of ecteinascidin 743.
Rinehart, Kenneth L.; Morales, Jose J.; Reid, Joel; Reymundo, Isabel; Floriano, Pablo; Gravalos, Lola Garcia, Metabolites of ecteinascidin 743 formed by human cytochrome CYP3A4.
Martin López, Ma Jesús; Francesch Solloso, Andrés; Cuevas Marchante, Maria del Carmen, Synthetic process for the manufacture of ecteinascidin compounds.
※ AI-Helper는 부적절한 답변을 할 수 있습니다.