The disclosure relates to compounds of the formula RCH2R' or a monomethyl or monoethyl ethers thereof, the compounds including their ethers each containing 29 carbon atoms in total, or esters or salts thereof;
wherein R is a fused ring system containing 3-5 rings and 4n+1 carbon atoms, (n = number of rings) at least three rings being aromatic when n is 3 or 4 and at least four rings being aromatic when n is 5, at least one of the aromatic rings containing a heteroatom; optionally substituted by 1-2 substituents; said substituents containing four carbon atoms when taken together and being the same or different and being selected from halogen, cyano; C1-4 alkyl or C1-4 alkoxy, each optionally substituted by OH or C1-2 alkoxy; halogen substitued C1-2 alkyl or C1-2 alkoxy; S(O)nR2 wherein n is an integer 0-2 and R2 is C1-2 alkyl optionally substitued by OH or C1-2 alkoxy; or Ar is optionally substituted by NR3R4 containing ≤5 carbon atoms wherein R3 and R4 are the same or different and each is C1-3 alkyl or NR3R4 forms a five- or six-membered heterocyclic ring optionally containing one or two additional heteroatoms; R' contains < eight carbon atoms and is a group
wherein m is 0 or 1;
R5 and R6 are the same or different and each is H or C1-5 alkyl optionally substituted by OH;
R7 and R8 are the same or different and each is H or C-3 alkyl;
-C-C- is a five- or six-membered saturated carbocyclic ring; R9 is H, CH3 or CH20H;
R10, R11 and R12 are the same or different and each is H or CH3 and R13 is H, CH3, OH, or CH30H;
except that R is not a tetracyclic ring system containing 15 to 17 ring atoms, three six membered carbocyclic rings and one five membered ring in which there is a heteratom.
Also disclosed are methods for the preparation of the said compounds, formulations containing them and their use in the treatment of tumours.
本发明涉及式 RCH2R'化合物或其单甲基或单
乙基醚,这些化合物包括其醚,或其酯或盐,每个醚总共含有 29 个碳原子;
其中 R 是含有 3-5 个环和 4n+1 个碳原子的熔合环系统,(n = 环数)当 n 为 3 或 4 时,至少有三个环是芳香环,当 n 为 5 时,至少有四个环是芳香环,芳香环中至少有一个含有杂原子;可选择被 1-2 个取代基取代;所述取代基含有四个碳原子,可相同或不同,选自卤素、
氰基、C1-4 烷基或 C1-4 烷基;C1-4烷基或C1-4烷氧基,各自可选择被OH或C1-2烷氧基取代; 被卤素取代的C1-2烷基或C1-2烷氧基; S(O)nR2,其中n是0-2的整数,R2是可选择被OH或C1-2烷氧基取代的C1-2烷基;或 Ar 被含有≤5 个碳原子的 NR3R4 任选取代,其中 R3 和 R4 相同或不同,且各自为 C1-3 烷基或 NR3R4 形成一个五元或六元杂环,可任选含有一个或两个额外的杂原子;R'含有 < 8 个碳原子,且是一个基团
其中 m 为 0 或 1;
R5 和 R6 相同或不同,各自为 H 或任选被 OH 取代的 C1-5 烷基;
R7 和 R8 相同或不同,各自为 H 或 C-3 烷基;
-R9 是 H、
CH3 或 CH20H;
R10、R11 和 R12 相同或不同,各自为 H 或 ,R13 为 H、 、OH 或 0H;
但 R 不是含有 15 至 17 个环原子的四环系统、三个六分子碳环和一个含有杂原子的五 分子环。
还公开了上述化合物的制备方法、含有这些化合物的制剂及其在治疗肿瘤中的用途。