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1. 发明专利

CS190399B2 PROCESS FOR PREPARING CAPHALEXINE 未知
公开(公告)号：CS190399B2
公开(公告)日：1979-05-31
申请号：CS63976
申请日：1972-05-10
申请人： RUBINFELD JOSEPH , LEMIEUX RAYMOND U , RAAP RINTJE
发明人： RUBINFELD JOSEPH , LEMIEUX RAYMOND U , RAAP RINTJE
IPC分类号： C07D501/04 , A23K20060101 , A61K20060101 , A61K31/43 , A61K31/545 , A61K31/546 , C07D20060101 , C07D499/00 , C07D501/00 , C07D501/02 , C07D501/10 , C07D501/18 , C07D501/22 , C07D501/58 , C07D501/60 , C07F7/18
摘要： 1391838 Penicillins and cephalosporins BRISTOL MYERS CO 11 May 1972 [11 May 1971] 22164/72 Heading C2C [Also in Division C3] A process for the rearrangement of a 6- acylamidopenicillanic acid sulphoxide of Formula I wherein R is the side chain of a fermentation produced penicillin into a 7-acylamido-3- methylceph-3-em-4-carboxylic acid of Formula II comprises heating the penicillanic acid sulphoxide (free acid form) in a weakly basic solvent in the presence of a catalyst comprising a strong acid either alone or in combination with a nitrogen base having a pKb of not less than 4. R may be hexyl, heptyl, thiophene-2-methyl, phenylmethyl, phenyl, phenoxymethyl or phenylmercaptomethyl. Alternatively, when R is one of the specified phenyl-containing groups. the phenyl radical may be substituted so that it is expressed by the formula in which Z is H, Cl, CH 3 , CH 3 0 or N0 2 . The above-mentioned rearrangement process may be employed in the preparation of cephalexin or hetacephalexin or non-toxic pharmaceutically acceptable salts thereof, and such antibiotic substances, thus obtained, may be formulated into pharmaceutical compositions together with an inert pharmaceutically acceptable carrier. Thus, a process for the preparation of cephalexin or a non-toxic pharmaceutically acceptable salt thereof comprises (A) oxidizing a fermentationproduced penicillin or a salt thereof to prqduce a 6-acylamido penicillanic acid sulphoxide of Formula I above; (B) converting the sulphoxide to a 7-acylamido-3-methylceph-3-em-4-carboxylic acid by the above-mentioned rearrangement process; (c) reacting the 4-carboxylic acid with a silylating agent of the formula or wherein R 2 , R 3 and R 4 are hydrogen, halogen, C 1 -C 7 alkyl, halo-(C 1 -C 7 alkyl), phenyl, benzyl, tolyl or dimethylaminophenyl, at least one of the R 2 , R 3 and R 4 groups being other than halogen or hydrogen; R 1 is C 1 -C 7 alkyl; m is 1 or 2; and X is halogen or wherein R 5 is hydrogen or C 1 -C 7 alkyl and R 8 is hydrogen, C 1 -C 7 alkyl or under anhydrous .conditions in an inert solvent, and in the presence of an acid-deactivating tertiary amine to form the corresponding silyl ester of the 4-carboxylic, acid; (D) reacting the silyl ester with an excess of a halogenating agent under anhydrous conditions, in an inert solvent and in the presence of an acid-deactivating tertiary amine, to form the corresponding imino halide; (E) reacting the imino halide with a C 1 -C 12 aliphatic alcohol or with a phenylalkyl alcohol (of 1-7 alkyl carbon atoms), to produce the corresponding imino ether; (F) splitting the imino bond of the imino ether by hydrolysis or alcoholysis, in the optional presence of a silylating agent as specified in step (C), to produce 7-amino-desacetoxycephalosporanic acid (7-ADCA) or, when the silylating agent is present, to produce the'mono- or-disilyi derivative of 7-ADCA; (G) if the mono-- or di-silyl derivative has not been prepared in step (F), then preparing such derivative by reacting the 7-ADCA with a silylating agent as specified in step (C); (H) N-acylating the silyl derivative with phenylglycyi chloride hydrochloride in an inert non-aqueous organic solvent; and (I) cleaving by hydrolysis or alcoholysis the silyl groups in the acylation product to form cephalexin, or, optionallly forming a nontoxic pharmaceutically acceptable salt of cephalexin. If the process is modified in one of the following'' ways, then the product is hetacephalexin instead of cephalexin: (1) in step (H) acetone is present in the N-acylation reaction mixture to provide silylated hetacephalexin, or (2) acetone is reacted with the product of step (H) to provide silylated hetacephalexin, the silylated material in each case then being cleaved as in step,. (I); or (3) acetone is reacted with the product of, step (I) to provide hetacephalexin or a non, toxic pharmaceutically acceptable salt thereof.

2. 发明专利

CS190400B2 PROCESS FOR PREPARING HETACEPHALEXINE 未知
公开(公告)号：CS190400B2
公开(公告)日：1979-05-31
申请号：CS64076
申请日：1972-05-10
申请人： RUBINFELD JOSEPH , LEMIEUX RAYMOND U , RAAP RINTJE
发明人： RUBINFELD JOSEPH , LEMIEUX RAYMOND U , RAAP RINTJE
IPC分类号： C07D501/04 , A23K20060101 , A61K20060101 , A61K31/43 , A61K31/545 , A61K31/546 , C07D20060101 , C07D499/00 , C07D501/00 , C07D501/02 , C07D501/10 , C07D501/18 , C07D501/22 , C07D501/58 , C07D501/60 , C07F7/18
摘要： 1391838 Penicillins and cephalosporins BRISTOL MYERS CO 11 May 1972 [11 May 1971] 22164/72 Heading C2C [Also in Division C3] A process for the rearrangement of a 6- acylamidopenicillanic acid sulphoxide of Formula I wherein R is the side chain of a fermentation produced penicillin into a 7-acylamido-3- methylceph-3-em-4-carboxylic acid of Formula II comprises heating the penicillanic acid sulphoxide (free acid form) in a weakly basic solvent in the presence of a catalyst comprising a strong acid either alone or in combination with a nitrogen base having a pKb of not less than 4. R may be hexyl, heptyl, thiophene-2-methyl, phenylmethyl, phenyl, phenoxymethyl or phenylmercaptomethyl. Alternatively, when R is one of the specified phenyl-containing groups. the phenyl radical may be substituted so that it is expressed by the formula in which Z is H, Cl, CH 3 , CH 3 0 or N0 2 . The above-mentioned rearrangement process may be employed in the preparation of cephalexin or hetacephalexin or non-toxic pharmaceutically acceptable salts thereof, and such antibiotic substances, thus obtained, may be formulated into pharmaceutical compositions together with an inert pharmaceutically acceptable carrier. Thus, a process for the preparation of cephalexin or a non-toxic pharmaceutically acceptable salt thereof comprises (A) oxidizing a fermentationproduced penicillin or a salt thereof to prqduce a 6-acylamido penicillanic acid sulphoxide of Formula I above; (B) converting the sulphoxide to a 7-acylamido-3-methylceph-3-em-4-carboxylic acid by the above-mentioned rearrangement process; (c) reacting the 4-carboxylic acid with a silylating agent of the formula or wherein R 2 , R 3 and R 4 are hydrogen, halogen, C 1 -C 7 alkyl, halo-(C 1 -C 7 alkyl), phenyl, benzyl, tolyl or dimethylaminophenyl, at least one of the R 2 , R 3 and R 4 groups being other than halogen or hydrogen; R 1 is C 1 -C 7 alkyl; m is 1 or 2; and X is halogen or wherein R 5 is hydrogen or C 1 -C 7 alkyl and R 8 is hydrogen, C 1 -C 7 alkyl or under anhydrous .conditions in an inert solvent, and in the presence of an acid-deactivating tertiary amine to form the corresponding silyl ester of the 4-carboxylic, acid; (D) reacting the silyl ester with an excess of a halogenating agent under anhydrous conditions, in an inert solvent and in the presence of an acid-deactivating tertiary amine, to form the corresponding imino halide; (E) reacting the imino halide with a C 1 -C 12 aliphatic alcohol or with a phenylalkyl alcohol (of 1-7 alkyl carbon atoms), to produce the corresponding imino ether; (F) splitting the imino bond of the imino ether by hydrolysis or alcoholysis, in the optional presence of a silylating agent as specified in step (C), to produce 7-amino-desacetoxycephalosporanic acid (7-ADCA) or, when the silylating agent is present, to produce the'mono- or-disilyi derivative of 7-ADCA; (G) if the mono-- or di-silyl derivative has not been prepared in step (F), then preparing such derivative by reacting the 7-ADCA with a silylating agent as specified in step (C); (H) N-acylating the silyl derivative with phenylglycyi chloride hydrochloride in an inert non-aqueous organic solvent; and (I) cleaving by hydrolysis or alcoholysis the silyl groups in the acylation product to form cephalexin, or, optionallly forming a nontoxic pharmaceutically acceptable salt of cephalexin. If the process is modified in one of the following'' ways, then the product is hetacephalexin instead of cephalexin: (1) in step (H) acetone is present in the N-acylation reaction mixture to provide silylated hetacephalexin, or (2) acetone is reacted with the product of step (H) to provide silylated hetacephalexin, the silylated material in each case then being cleaved as in step,. (I); or (3) acetone is reacted with the product of, step (I) to provide hetacephalexin or a non, toxic pharmaceutically acceptable salt thereof.

3. 发明专利

CS190367B2 PROCESS FOR PREPARING DERIVATIVES OF CEPHALOSPORINE 未知
公开(公告)号：CS190367B2
公开(公告)日：1979-05-31
申请号：CS312972
申请日：1972-05-10
申请人： RUBINFELD JOSEPH , LEMIEUX RAYMOND U , RAAP RINTJE
发明人： RUBINFELD JOSEPH , LEMIEUX RAYMOND U , RAAP RINTJE
IPC分类号： C07D501/04 , A23K20060101 , A61K20060101 , A61K31/43 , A61K31/545 , A61K31/546 , C07D20060101 , C07D499/00 , C07D501/00 , C07D501/02 , C07D501/10 , C07D501/18 , C07D501/22 , C07D501/58 , C07D501/60 , C07F7/18
摘要： 1391838 Penicillins and cephalosporins BRISTOL MYERS CO 11 May 1972 [11 May 1971] 22164/72 Heading C2C [Also in Division C3] A process for the rearrangement of a 6- acylamidopenicillanic acid sulphoxide of Formula I wherein R is the side chain of a fermentation produced penicillin into a 7-acylamido-3- methylceph-3-em-4-carboxylic acid of Formula II comprises heating the penicillanic acid sulphoxide (free acid form) in a weakly basic solvent in the presence of a catalyst comprising a strong acid either alone or in combination with a nitrogen base having a pKb of not less than 4. R may be hexyl, heptyl, thiophene-2-methyl, phenylmethyl, phenyl, phenoxymethyl or phenylmercaptomethyl. Alternatively, when R is one of the specified phenyl-containing groups. the phenyl radical may be substituted so that it is expressed by the formula in which Z is H, Cl, CH 3 , CH 3 0 or N0 2 . The above-mentioned rearrangement process may be employed in the preparation of cephalexin or hetacephalexin or non-toxic pharmaceutically acceptable salts thereof, and such antibiotic substances, thus obtained, may be formulated into pharmaceutical compositions together with an inert pharmaceutically acceptable carrier. Thus, a process for the preparation of cephalexin or a non-toxic pharmaceutically acceptable salt thereof comprises (A) oxidizing a fermentationproduced penicillin or a salt thereof to prqduce a 6-acylamido penicillanic acid sulphoxide of Formula I above; (B) converting the sulphoxide to a 7-acylamido-3-methylceph-3-em-4-carboxylic acid by the above-mentioned rearrangement process; (c) reacting the 4-carboxylic acid with a silylating agent of the formula or wherein R 2 , R 3 and R 4 are hydrogen, halogen, C 1 -C 7 alkyl, halo-(C 1 -C 7 alkyl), phenyl, benzyl, tolyl or dimethylaminophenyl, at least one of the R 2 , R 3 and R 4 groups being other than halogen or hydrogen; R 1 is C 1 -C 7 alkyl; m is 1 or 2; and X is halogen or wherein R 5 is hydrogen or C 1 -C 7 alkyl and R 8 is hydrogen, C 1 -C 7 alkyl or under anhydrous .conditions in an inert solvent, and in the presence of an acid-deactivating tertiary amine to form the corresponding silyl ester of the 4-carboxylic, acid; (D) reacting the silyl ester with an excess of a halogenating agent under anhydrous conditions, in an inert solvent and in the presence of an acid-deactivating tertiary amine, to form the corresponding imino halide; (E) reacting the imino halide with a C 1 -C 12 aliphatic alcohol or with a phenylalkyl alcohol (of 1-7 alkyl carbon atoms), to produce the corresponding imino ether; (F) splitting the imino bond of the imino ether by hydrolysis or alcoholysis, in the optional presence of a silylating agent as specified in step (C), to produce 7-amino-desacetoxycephalosporanic acid (7-ADCA) or, when the silylating agent is present, to produce the'mono- or-disilyi derivative of 7-ADCA; (G) if the mono-- or di-silyl derivative has not been prepared in step (F), then preparing such derivative by reacting the 7-ADCA with a silylating agent as specified in step (C); (H) N-acylating the silyl derivative with phenylglycyi chloride hydrochloride in an inert non-aqueous organic solvent; and (I) cleaving by hydrolysis or alcoholysis the silyl groups in the acylation product to form cephalexin, or, optionallly forming a nontoxic pharmaceutically acceptable salt of cephalexin. If the process is modified in one of the following'' ways, then the product is hetacephalexin instead of cephalexin: (1) in step (H) acetone is present in the N-acylation reaction mixture to provide silylated hetacephalexin, or (2) acetone is reacted with the product of step (H) to provide silylated hetacephalexin, the silylated material in each case then being cleaved as in step,. (I); or (3) acetone is reacted with the product of, step (I) to provide hetacephalexin or a non, toxic pharmaceutically acceptable salt thereof.

4. 发明申请

WO0174401A3 CAMPTOTHECIN COMPLEXES 审中-公开
标题翻译： CAMPTOTHECIN复合物
公开(公告)号：WO0174401A3
公开(公告)日：2002-05-02
申请号：PCT/US0106829
申请日：2001-03-02
申请人： SUPERGEN INC , RUBINFELD JOSEPH , WRENN SIMEON M
发明人： RUBINFELD JOSEPH , WRENN SIMEON M
IPC分类号： A61K31/4745 , A61K47/48 , B65G21/14
CPC分类号： B82Y5/00 , A61K31/4745 , A61K47/6901 , A61K47/6951 , B65G21/14
摘要： Disclosed are compositions that include a camptothecin and an amorphous cyclodextrin. The camptothecin may be substituted or unsubstituted. Also disclosed are methods of treating undesirable or uncontrolled cell proliferation by administering the inventive compositions. Finally, implants including an implant structure and the inventive composition are disclosed.
摘要翻译：公开了包括喜树碱和无定形环糊精的组合物。喜树碱可以是取代或未取代的。还公开了通过施用本发明组合物治疗不期望或不受控制的细胞增殖的方法。最后，公开了包括植入物结构和本发明组合物的植入物。

5. 发明申请

WO2005034845A3 COMPOSITIONS AND METHODS FOR TREATMENT OF CANCER 审中-公开
标题翻译：用于治疗癌症的组合物和方法
公开(公告)号：WO2005034845A3
公开(公告)日：2005-09-15
申请号：PCT/US2004022367
申请日：2004-07-13
申请人： SUPERGEN INC , RUBINFELD JOSEPH
发明人： RUBINFELD JOSEPH
IPC分类号： A61K31/16 , A61K31/706 , A61K31/7072 , A61K31/40
CPC分类号： A61K31/706 , A61K31/16 , A61K2300/00
摘要： Compositions and methods for treatment of conditions related to the overexpression of EZH2, such as late stage prostate cancer, using a DNA methylation inhibitor and/or a histone deacetylase inhibitor, optionally in combination with an EZH2 antagonist and/or an antineoplastic agent, to specifically target diseases associated with EZH2 overexpression. Further provided are reagents and kits for treatment of EZH2 overexpression.
摘要翻译：使用DNA甲基化抑制剂和/或组蛋白去乙酰化酶抑制剂，任选地与EZH2拮抗剂和/或抗肿瘤剂组合和治疗与EZH2过表达相关的病症（例如晚期前列腺癌）目标疾病与EZH2过表达。进一步提供了用于治疗EZH2过表达的试剂和试剂盒。

6. 发明申请

WO2002067681A1 RESTORE CANCER-SUPPRESSING FUNCTIONS TO NEOPLASTIC CELLS THROUGH DNA HYPOMETHYLATION 审中-公开
标题翻译：通过DNA高效液相色谱法恢复对巨噬细胞的抑制功能
公开(公告)号：WO2002067681A1
公开(公告)日：2002-09-06
申请号：PCT/US2002/004135
申请日：2002-02-11
申请人： SUPERGEN, INC. , RUBINFELD, Joseph , CHANG, Lucy , DIMARTINO, Jorge
发明人： RUBINFELD, Joseph , CHANG, Lucy , DIMARTINO, Jorge
IPC分类号： A01N43/04
CPC分类号： A61K31/495 , A61K31/00 , A61K31/57 , A61K39/39558 , A61K2300/00
摘要： Compositions and methods are provided for treating diseases associated with abnormal cell proliferation such as cancer by storing inherent tumor-suppressing functions of neoplastic cells through DNA hypomethylation. The method comprises: delivering to a patient suffering from cancer a therapeutically effective amount of a DNA mehtylation inhibitor such as decitabine, in combination with an effective amount of an anti-neoplastic agent whose activity as an anti-neoplastic agent in vivo is adversely affected by aberrant DNA methylation. The anti-neoplastic agent can be an alkylating agent, an antibiotic agent, an antimetabolic agent, a retinoid, a hormonal agent, a plant-derived agent, an anti-angiogenesis agent and a biologic agent such as monoclonal antibody and interferon.
摘要翻译：通过DNA低位甲基化存储肿瘤细胞的固有肿瘤抑制功能，提供了用于治疗与异常细胞增殖相关的疾病的组合物和方法。该方法包括：向患有癌症的患者递送治疗有效量的DNA甲氧基化抑制剂例如地西他滨，与有效量的抗肿瘤剂组合，其抗体活性作为体内抗肿瘤剂受到不利影响异常DNA甲基化。抗肿瘤剂可以是烷化剂，抗生素，抗代谢剂，类视色素，激素，植物衍生剂，抗血管生成剂和生物制剂如单克隆抗体和干扰素。

7. 发明申请

WO0180843A3 INHIBITION OF ABNORMAL CELL PROLIFERATION WITH CAMPTOTHECIN AND COMBINATIONS INCLUDING THE SAME 审中-公开
标题翻译：抑制异常细胞增殖与包涵体的组合
公开(公告)号：WO0180843A3
公开(公告)日：2002-08-15
申请号：PCT/US0112848
申请日：2001-04-19
申请人： SUPERGEN INC , RUBINFELD JOSEPH
发明人： RUBINFELD JOSEPH
IPC分类号： A61K31/44 , A61K31/4745 , A61K31/70 , A61K45/06 , A61K31/437 , A61P35/00
CPC分类号： A61K45/06 , A61K31/44 , A61K31/4745 , A61K31/70 , A61K2300/00
摘要： A method for treating diseases associated with abnormal cell proliferation comprises delivering to a patient in need of treatment a compound selected from the group consisting of 20(S)-comptothecin, analog of 20(S)-comptothecin, derivative of 20(S)-camptothecin, prodrug of 20(S)-camptothecin, and pharmaceutically active metabolite of 20(S)-camptothecin, in combination with an effective amount of one or more agents selected form the group consisting of alkylating agent, antibiotic agent, an alkylating agent, antibiotic agent, antimetabolic agent, hormonal agent, plant-derived agent, anti-angiogenesis agent and biologic agent. The method can be used to treat benign tumors, malignant or metastatic tumors, leukemia and diseases associated with abnormal angiogenesis.
摘要翻译：用于治疗与异常细胞增殖相关的疾病的方法包括向需要治疗的患者递送选自20（S） - 兴奋素，类似物20（S） - 兴奋剂，20（S） - 喜树碱，20（S） - 喜树碱的前药和20（S） - 喜树碱的药物活性代谢物，与有效量的一种或多种选自烷基化剂，抗生素，烷化剂，抗生素，抗代谢剂，激素，植物衍生剂，抗血管生成剂和生物制剂。该方法可用于治疗良性肿瘤，恶性或转移性肿瘤，白血病和与异常血管发生相关的疾病。

8. 发明申请

WO2003103672A1 SEQUENTIAL THERAPY COMPRISING A 20(S)-CAMPTOTHECIN AND AN ANTHRACYCLINE 审中-公开
标题翻译：包含20（S） - 角叉菜胶和ANTHRACYCLINE的顺序疗法
公开(公告)号：WO2003103672A1
公开(公告)日：2003-12-18
申请号：PCT/US2003/016744
申请日：2003-05-28
申请人： SUPERGEN, INC. , RUBINFELD, Joseph
发明人： RUBINFELD, Joseph
IPC分类号： A61K31/4745
CPC分类号： A61K31/70 , A61K45/06
摘要： A method is provided for treating a patient having a disease associated with undesirable or uncontrolled cell proliferation. The method comprises: administering to the patient an anthracycline for a period of time during which a 20(S)-camptothecin is not present in a pharmacologically active form in patient's blood, and administering a 20(S)-camptothecin to the patient.
摘要翻译：提供了一种治疗患有与不良或不受控制的细胞增殖相关的疾病的患者的方法。所述方法包括：向患者施用蒽环类药物，其中20（S） - 喜树碱在患者血液中不以药理活性形式存在，并且向患者施用20（S） - 喜树碱。

9. 发明申请

WO2003065995A3 METHOD FOR TREATING DISEASES ASSOCIATED WITH ABNORMAL KINASE ACTIVITY 审中-公开
公开(公告)号：WO2003065995A3
公开(公告)日：2003-08-14
申请号：PCT/US2003/003537
申请日：2003-02-06
申请人： SUPERGEN, INC. , LYONS, John , RUBINFELD, Joseph
发明人： LYONS, John , RUBINFELD, Joseph
IPC分类号： A61K39/00
摘要： Methods are provided for treating diseases associated with abnormal activity of kinases such as chronic myelogenous leukemia. The method comprises: administering a DNA methylation inhibitor to the patient in therapeutically effective amount; and administering a kinase inhibitor such as imatinib mesylate to the patient in therapeutically effective amount, such that the in vivo activity of the kinase is reduced relative to that prior to the treatment. The method can be used to treat cancer associated with abnormal activity of kinases such as phosphatidylinositol 3'-kinase (P13K), protein kinases including serine/threonine kinases such as Raf kinases, protein kinase kinases such as MEK, and tyrosine kinases such as those in the epidermal growth factor receptor family (EGFR), platelet-derived growth factor receptor family (PDGFR), vascular endothelial growth factor receptor (VEGFR) family, nerve growth factor receptor family (NGFR), fibroblast growth factor receptor family (FGFR) insulin receptor family, ephrin receptor family, Met family, Ror family, c-kit family, Src family, Fes family, JAK family, Fak family, Btk family, Syk/ZAP-70 family, and Abl family.

10. 发明申请

WO2003065995A2 METHOD FOR TREATING DISEASES ASSOCIATED WITH ABNORMAL KINASE ACTIVITY 审中-公开
标题翻译：用于治疗与异常激酶活性相关的疾病的方法
公开(公告)号：WO2003065995A2
公开(公告)日：2003-08-14
申请号：PCT/US2003/003537
申请日：2003-02-06
申请人： SUPERGEN, INC. , LYONS, John , RUBINFELD, Joseph
发明人： LYONS, John , RUBINFELD, Joseph
IPC分类号： A61K
CPC分类号： A61K31/7068 , A61K31/00 , A61K31/706 , A61K45/06
摘要： Methods are provided for treating diseases associated with abnormal activity of kinases such as chronic myelogenous leukemia. The method comprises: administering a DNA methylation inhibitor to the patient in therapeutically effective amount; and administering a kinase inhibitor such as imatinib mesylate to the patient in therapeutically effective amount, such that the in vivo activity of the kinase is reduced relative to that prior to the treatment. The method can be used to treat cancer associated with abnormal activity of kinases such as phosphatidylinositol 3'-kinase (P13K), protein kinases including serine/threonine kinases such as Raf kinases, protein kinase kinases such as MEK, and tyrosine kinases such as those in the epidermal growth factor receptor family (EGFR), platelet-derived growth factor receptor family (PDGFR), vascular endothelial growth factor receptor (VEGFR) family, nerve growth factor receptor family (NGFR), fibroblast growth factor receptor family (FGFR) insulin receptor family, ephrin receptor family, Met family, Ror family, c-kit family, Src family, Fes family, JAK family, Fak family, Btk family, Syk/ZAP-70 family, and Abl family.
摘要翻译：提供了用于治疗与慢性粒细胞白血病等激酶异常活动相关的疾病的方法。该方法包括：以治疗有效量向患者施用DNA甲基化抑制剂; 并以治疗有效量向患者施用激酶抑制剂如甲磺酸伊马替尼，使得激酶的体内活性相对于治疗前的活性降低。该方法可用于治疗与磷脂酰肌醇3'-激酶（P13K），蛋白激酶（包括丝氨酸/苏氨酸激酶，如Raf激酶，蛋白激酶激酶如MEK）和酪氨酸激酶（如酪氨酸激酶）等异常活性相关的癌症。在表皮生长因子受体家族（EGFR），血小板衍生生长因子受体家族（PDGFR），血管内皮生长因子受体（VEGFR）家族，神经生长因子受体家族（NGFR），成纤维细胞生长因子受体家族（FGFR）胰岛素受体家族，ephrin受体家族，Met家族，Ror家族，c-kit家族，Src家族，Fes家族，JAK家族，Fak家族，Btk家族，Syk / ZAP-70家族和Abl家族。

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