The present invention provides a compound of the formula (I):
or a monomethyl or monoethyl ether thereof, the compound of formula (I) including the said ethers containing no more than 29 carbon atoms in total; an ester thereof; a salt thereof; wherein Ar is a 6,6,6,5 tetracyclic aromatic ring system having 15 to 17 ring atoms, the five membered ring containing one heteroatom, optionally substituted by one or two substituents, said substituents containing not more than four carbon atoms in total when taken together and being the same of different and are selected from halogen; cyano; Cl-4 alkyl or Cl-4 alkoxy, each optionally substituted by hydroxy or Cl-2 alkoxy; halogen substituted Cl-2 alkyl or Cl-2 alkoxy; a group (S(O)nR2 wherein n is an integer 0, 1 or 2 and R2 is Cl-2 alkyl optionally substituted by hydroxy or Cl-2 alkoxy; or Ar is optionally substituted by a group NR3R4 containing not more than 5 carbon atoms wherein R3 and R4 are the same or different and each is a C1-3 alkyl group or NR3R4 forms a five-or six-membered heterocyclic ring optionally containing one or two additional heteroatoms; R1 contains not more than eight carbon atoms and is a group
wherein m is 0 or 1;
R5 and R6 are the same or different and each is hydrogen or
Cl-5 alkyl optionally substituted by hydroxy;
R7 and R8 are the same or different and each is hydrogen or
C1-3 alkyl;
C-C is a five-or-six-membered saturated carbocyclic ring;
R9 is hydrogen, methyl or hydroxymethyl;
R10, R11 and R12 are the same or different and each is hydrogen or methyl;
R13 is hydrogen, methyl, hydroxy or hydroxymethyl.
Also provided are methods for the preparation of the compounds of formula (I), intermediates in their preparations and pharmaceutical formulations containing them.
The compounds of the formula (I) are useful in the treatment of tumours.
本发明提供了一种式 (I) 的化合物:
或其单甲基或单
乙基醚,式(I)化合物包括总共含有不超过 29 个碳原子的上述醚;其酯;其盐;其中 Ar 是具有 15 至 17 个环原子的 6,6,6,5 四环芳香环系统,该五元环含有一个杂原子,可任选被一个或两个取代基取代,所述取代基在一起时总共含有不超过四个碳原子且相同或不同,并选自卤素;
氰基;Cl-4 烷基或 Cl-4 烷氧基,各自可任选被羟基或 Cl-2 烷氧基取代;卤素取代的 Cl-2 烷基或 Cl-2 烷氧基;卤素取代的 Cl-2 烷基或 Cl-2 烷氧基;Cl-4 烷基或 Cl-4 烷氧基,各自任选被羟基或 Cl-2 烷氧基取代;卤素取代的 Cl-2 烷基或 Cl-2 烷氧基;基团(S(O)nR2,其中 n 为整数 0、1 或 2,R2 为任选被羟基或 Cl-2 烷氧基取代的 Cl-2 烷基;或 Ar 任选被含有不超过 5 个碳原子的基团 NR3R4 取代,其中 R3 和 R4 相同或不同,且各自为 C1-3 烷基,或 NR3R4 构成可选含有一个或两个额外杂原子的五元或六元杂环; R1 含有不超过 8 个碳原子,且是一个基团; R3R4 构成可选含有一个或两个额外杂原子的五元或六元杂环,其中 R3 和 R4 相同或不同,且各自为 C1-3 烷基,或 NR3R4 构成可选含有一个或两个额外杂原子的五元或六元杂环。
其中 m 为 0 或 1;
R5 和 R6 相同或不同,各自为氢或
任选被羟基取代的 Cl-5 烷基;
R7 和 R8 相同或不同,各自为氢或
C1-3 烷基;
C-C 是五或六元饱和碳环;
R9 是氢、甲基或羟甲基;
R10、R11 和 R12 相同或不同,各自为氢或甲基;
R13 是氢、甲基、羟基或羟甲基。
此外,还提供了式 (I) 化合物、其制备过程中的中间体以及含有这些化合物的药物制剂的制备方法。
式(I)化合物可用于治疗肿瘤。