公开(公告)号：US20050272801A1

公开(公告)日：2005-12-08

申请号：US11167054

申请日：2005-06-24

申请人： Shirley Gasper ,  Robert West ,  Theresa Martinez ,  Kirk Robbins ,  Patricia McKernan ,  Nand Baindur ,  Virender Labroo ,  Gregory Mundy

发明人： Shirley Gasper ,  Robert West ,  Theresa Martinez ,  Kirk Robbins ,  Patricia McKernan ,  Nand Baindur ,  Virender Labroo ,  Gregory Mundy

IPC分类号： A23L1/30 ,  A61K31/00 ,  A61K31/192 ,  A61K31/22 ,  A61K31/225 ,  A61K31/366 ,  A61K31/40 ,  A61K31/404 ,  A61K31/405 ,  A61K31/4409 ,  A61K31/47 ,  A61K31/505 ,  A61K45/06 ,  A61P1/02 ,  A61P3/14 ,  A61P5/20 ,  A61P19/08 ,  A61P19/10 ,  C07D207/416 ,  C07D213/54 ,  C07D215/14

CPC分类号： C07D215/14 ,  A23L33/10 ,  A61K31/00 ,  A61K31/192 ,  A61K31/22 ,  A61K31/225 ,  A61K31/366 ,  A61K31/40 ,  A61K31/404 ,  A61K31/405 ,  A61K31/505 ,  A61K45/06 ,  A61K2300/00

摘要： Compounds of the formula wherein X in each of formulas (1) and (2) represents a substituted or unsubstituted alkylene, alkenylene, or alkynylene linker of 2-6C; Y is of the formula or a stereoisomer thereof, wherein R1 is substituted or unsubstituted alkyl; each R2 is independently H, hydroxy, alkoxy (1-6C) or lower alkyl (1-4C); R3 is H, hydroxy, or alkoxy (1-6C); or Y is of the formula wherein each n is 1, Z is N, K comprises a substituted or unsubstituted aromatic carbocyclic or heterocyclic ring system which may optionally be spaced from the linkage position shown in formula (7) by a linker of 1-2C, or in formula (7), Z may be spaced from the carbon bonded to X by ═CR6— wherein R6 is H or linear, branded or cyclic alkyl (1-6C), R5 is H or linear, branched or cyclic alkyl, and R′ represents a cation, H or a substituted or unsubstituted alkyl group of 1-6C, promote bone formation and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyroidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery, and post-dental implantation. Also disclosed is a method to identify additional compounds which are inhibitors of enzymes in the isoprenoid scheme especially of HMG-CoA reductase which results in prenylation of proteins and in the synthesis of steroids or of inhibitors of their production which are useful in treating bone disorders.

摘要翻译： 式（1）和（2）中的X表示取代或未取代的2-6C的亚烷基，亚烯基或亚炔基接头; Y是下式或其立体异构体，其中R 1是取代或未取代的烷基; 每个R 2独立地是H，羟基，烷氧基（1-6C）或低级烷基（1-4C）; R 3是H，羟基或烷氧基（1-6C）; 或Y具有下式：其中每个n是1，Z是N，K包括取代或未取代的芳族碳环或杂环系统，其可以任选地与式（7）所示的连接位置间隔1-2- ，或式（7）中，Z可以与通过-CR 6键合到X的碳隔开，其中R 6是H或直链的，有品牌的或环状的烷基（ 1-6C）中，R 5是H或直链，支链或环状的烷基，R'表示阳离子，H或1-6C的取代或未取代的烷基，促进骨形成，因此 可用于治疗骨质疏松症，骨折或缺陷，原发性或继发性甲状旁腺功能亢进，牙周病或缺损，转移性骨病，溶骨性骨病，整形外手术，假体后关节手术和牙后植入术。 还公开了一种鉴定另外的化合物的方法，该化合物是类异戊二烯方案中尤其是HMG-CoA还原酶中的酶的抑制剂，其导致蛋白质的异戊烯化，以及合成类固醇或其生产抑制剂，其可用于治疗骨骼疾病。