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109 条记录 (耗时 0.055 秒)

    Methods and compositions for degradation and/or inhibition of HER-family tyrosine kinases
    21.
    发明授权
    Methods and compositions for degradation and/or inhibition of HER-family tyrosine kinases 有权
    用于降解和/或抑制HER-家族酪氨酸激酶的方法和组合物

    公开(公告)号：US07238682B1

    公开(公告)日：2007-07-03

    申请号：US09937192

    申请日：2000-04-07

    申请人： Neal Rosen ,  Scott D. Kuduk ,  Samuel J. Danishefsky ,  Furzhong F. Zheng ,  Laura Sepp-Lorenzino ,  Ouatek Ouerfelli

    发明人： Neal Rosen ,  Scott D. Kuduk ,  Samuel J. Danishefsky ,  Furzhong F. Zheng ,  Laura Sepp-Lorenzino ,  Ouatek Ouerfelli

    IPC分类号： C07D403/02 ,  A61K31/395 ,  A61P35/00

    CPC分类号： C07D403/12

    摘要： Bifunctional molecules comprising two hsp-binding moieties which bind to hsp90 in the pocket to which ansamycin antibiotics bind connected via a linker are effective for inducing the degradation and/or inhibition of HER-family tyrosine kinases. For example, a compound of two geldanamycin moities joined by a four-carbon linker provides selective degradation of HER-family tyrosine kinases, without substantially affecting other kinases. These compounds can be used for treatment of HER-positive cancers with reduced toxicity, since these compounds potently kill cancer cells but affect fewer proteins than geldanamycin.

    摘要翻译： 包含两个hsp结合部分的双功能分子对于诱导HER​​-家族酪氨酸激酶的降解和/或抑制是有效的，所述两个hsp结合部分与口服中与安莎霉素抗生素通过接头连接的hsp90结合。 例如，通过四碳连接物连接的两个格尔德霉素部分的化合物提供HER-家族酪氨酸激酶的选择性降解，而基本上不影响其它激酶。 这些化合物可用于治疗具有降低毒性的HER阳性癌症，因为这些化合物有效杀死癌细胞，但影响比格尔德霉素少的蛋白质。

    Synthetic compounds which bind to H. pylori, and uses thereof
    24.
    发明授权
    Synthetic compounds which bind to H. pylori, and uses thereof 失效
    与幽门螺杆菌结合的合成化合物及其用途

    公开(公告)号：US5543505A

    公开(公告)日：1996-08-06

    申请号：US213053

    申请日：1993-03-15

    申请人： Samuel J. Danishefsky ,  John T. Randolph

    发明人： Samuel J. Danishefsky ,  John T. Randolph

    IPC分类号： A61K38/00 ,  C07H3/06 ,  C07H17/04 ,  C07K9/00 ,  C07K14/765 ,  C07H15/00 ,  C07H15/06 ,  C07H17/00 ,  C07K1/00

    CPC分类号： C07K14/765 ,  C07H17/04 ,  C07H3/06 ,  C07K9/00 ,  A61K38/00

    摘要： The present invention provides a compound having the structure: ##STR1## wherein A is selected from the group consisting of (i) an amino acid bearing an .omega.-amino group or an .omega.--(C.dbd.O)-- group, (ii) an amino acid residue of a peptide, which residue bears an .omega.-amino group or an .omega.-(C.dbd.O)-- group, and (iii) an amino acid residue of a protein, which residue bears an .omega.-amino group or an .omega.-(C.dbd.O)-- group; wherein R.sub.1 is H, OH, NH.sub.2 or NHR.sub.4, where R.sub.4 is SO.sub.2 Ph, a linear or branched chain alkyl or acyl group, or an aryl group; wherein M is a saccharide wherein n is an integer from 0 to 18, and where n is greater than 1, each M is independently the same or different; wherein p is either 0 or 1; wherein R.sub.2, R.sub.3, R.sub.5 and R.sub.6 are independently the same or different and are H or OH, with the proviso that R.sub.2 and R.sub.3 are not both OH, and R.sub.5 and R.sub.6 are not both OH; wherein X and Y are independently the same or different and are H.sub.2 or O; and wherein k is an integer greater than or equal to 1, with the proviso that when A is an amino acid bearing an .omega.-amino group or an .omega.-(C.dbd.O)-- group, k is equal to 1.

    摘要翻译： 本发明提供具有以下结构的化合物：其中A选自（i）具有ω-氨基或ω-（C = O） - 基团的氨基酸 ，（ii）肽的氨基酸残基，该残基具有ω-氨基或ω-（C = O） - 基团，和（iii）蛋白质的氨基酸残基，该残基具有ω- 氨基或ω-（C = O） - 基团; 其中R 1是H，OH，NH 2或NHR 4，其中R 4是SO 2 Ph，直链或支链烷基或酰基或芳基; 其中M是糖，其中n是0至18的整数，并且其中n大于1，每个M独立地相同或不同; 其中p是0或1; 其中R2，R3，R5和R6独立地相同或不同，为H或OH，条件是R2和R3不同时为OH，R5和R6不同时为OH; 其中X和Y独立地相同或不同，为H 2或O; 并且其中k是大于或等于1的整数，条件是当A是具有ω-氨基或ω-（C = O） - 基团的氨基酸时，k等于1。

    Preparation of camptothecin analogs
    25.
    发明授权
    Preparation of camptothecin analogs 失效
    喜树碱类似物的制备

    公开(公告)号：US5541327A

    公开(公告)日：1996-07-30

    申请号：US340034

    申请日：1994-11-14

    申请人： Samuel J. Danishefsky ,  William G. Bornmann ,  Wang Shen ,  Craig A. Coburn

    发明人： Samuel J. Danishefsky ,  William G. Bornmann ,  Wang Shen ,  Craig A. Coburn

    IPC分类号： C07D491/14 ,  C07D491/147 ,  C07D491/22 ,  C07H17/00

    CPC分类号： C07D491/14 ,  C07H17/00

    摘要： Substituted analogues of camptothecin possessing cytotoxic activity towards cancer cells, of the general structure: ##STR1## wherein E is H, CO.sub.2 R, CONH.sub.2, CONHR, CONR.sub.2, acyl, or CN; X is H, OH, or OR; R.sup.1, R.sup.2, R.sup.3, and R.sup.4 are independently the same or different and are H, or a linear or branched chain alkyl, alkylaryl, or hydroxyalkyl group, or an aryl group; R.sup.5, R.sup.6, R.sup.7, R.sup.8, and R.sup.9 are independently the same or different and are H, or a linear or branched chain alkyl, alkylaryl, alkoxy, hydroxyalkyl, or aminoalkoxy group, or an aryl or aryloxy group, or a C-glycal, or CO.sub.2 R, nitro, cyano, Cl, F, Br, I, SR.sup.10, NR.sup.11 R.sup.12, OR.sup.13 ; R is H, or a linear or branched chain alkyl, alkylaryl, or hydroxyalkyl group, or an aryl group; R.sup.10, R.sup.11 and R.sup.12 are independently the same or different and are H, or a linear or branched chain alkyl, alkylaryl, hydroxyalkyl, or acyl group, or an aryl group; R.sup.13 is glycosyl; n is 0 or 1; with the proviso that when R.sup.1 is ethyl, and n is 0, E, R.sup.2, R.sup.3, and R.sup.4 are not all H. Intermediate compounds leading to the camptothecin analogues comprise substituted tricyclic compounds which consist of rings C, D, and E fused together. Methods for preparing the analogues involve condensation of such intermediates with variably substituted protected .alpha.-aminobenzaldehydes.

    摘要翻译： 具有一般结构的具有对癌细胞的细胞毒性活性的喜树碱的取代类似物：其中E是H，CO 2 R，CONH 2，CONHR，CONR 2，酰基或CN; X是H，OH或OR; R 1，R 2，R 3和R 4独立地相同或不同，为H，或直链或支链烷基，烷基芳基或羟烷基或芳基; R 5，R 6，R 7，R 8和R 9独立地相同或不同，为H，或直链或支链烷基，烷基芳基，烷氧基，羟基烷基或氨基烷氧基，或芳基或芳氧基或C- ，或CO 2 R，硝基，氰基，Cl，F，Br，I，SR10，NR 11 R 12，OR 13; R为H或直链或支链烷基，烷基芳基或羟烷基或芳基; R 10，R 11和R 12独立地相同或不同，为H，或直链或支链烷基，烷基芳基，羟基烷基或酰基或芳基; R13是糖基; n为0或1; 条件是当R 1为乙基且n为0时，E，R 2，R 3和R 4不全为H.导致喜树碱类似物的中间体化合物包含由稠合在一起的环C，D和E组成的取代的三环化合物 。 制备类似物的方法涉及这种中间体与可变取代的被保护的α-氨基苯甲醛的缩合。