公开(公告)号：US4419522A

公开(公告)日：1983-12-06

申请号：US315182

申请日：1981-10-26

申请人： Ilona Elekes ,  Laszlo Institoris ,  Kalman Medzihradsz ,  Laszlo tvos ,  Hedvig Medzihradszky-Schweiger ,  Katalin De Gleria ,  Janos Sugar ,  Somfai Relle ,  Sandor Eckhardt ,  Ivan Hidy ,  Sandor Kerpel-Fronius

发明人： Ilona Elekes ,  Laszlo Institoris ,  Kalman Medzihradsz ,  Laszlo tvos ,  Hedvig Medzihradszky-Schweiger ,  Katalin De Gleria ,  Janos Sugar ,  Somfai Relle ,  Sandor Eckhardt ,  Ivan Hidy ,  Sandor Kerpel-Fronius

IPC分类号： C07C69/003 ,  A61K31/22 ,  A61K31/225 ,  A61K31/335 ,  A61K31/336 ,  A61P35/00 ,  A61P35/02 ,  C07D303/16 ,  C07D407/12 ,  C07C69/63 ,  C07C69/635 ,  C07C69/65 ,  C07C69/653 ,  C07C69/657

CPC分类号： C07D303/16

摘要： The invention relates to new hexitols having the general formula (I) and (II), ##STR1## wherein the hexitol skeleton is dulcitol, mannitol or iditol,X represents halogen, preferably bromine,R is a saturated or unsaturated C.sub.4-10 alkylcarbonyl group which also contains a free carboxy group, andR.sup.1 is hydrogen, a saturated or unsaturated C.sub.4-10 alkylcarbonyl group which also contains a free carboxy group, a saturated or unsaturated C.sub.2-10 alkylcarbonyl group, a saturated or unsaturated C.sub.4-10 alkylcarbonyl group which also contains an alkoxycarbonyl group, or a saturated or unsaturated C.sub.8-10 aralkylcarbonyl group,and salts of these compounds. The new compounds according to the invention have tumor-inhibiting affects.The above compounds are prepared according to the invention so that(a) a compound of the general formula (IX), whereinthe hexitol skeleton is dulcitol, mannitol or iditol,Q is a saturated or unsaturated C.sub.11-17 alkylcarbonyl group which also contains a benzyloxycarbonyl group, andQ.sup.1 is hydrogen, a saturated or unsaturated C.sub.2-10 alkylcarbonyl group, a saturated or unsaturated C.sub.4-10 alkylcarbonyl group which also contains an alkoxycarbonyl group, a saturated or unsaturated C.sub.11-17 alkylcarbonyl group which also contains a benzyloxycarbonyl group, or a saturated or unsaturated C.sub.8-10 aralkylcarbonyl group, is hydrogenated in an anhydrous solvent in the presence of a weakly active catalyst which does not affect the epoxide ring, or(b) a 1,2-5,6-dianhydrohexitol of the general formula (X), wherein the hexitol skeleton is dulcitol, mannitol or iditol, is reacted with a dicarboxylic acid anhydride of the general formula (XI), wherein A is a C.sub.2-10 alkyl, aralkyl or aryl group, or(c) a compound of the general formula (I) is reacted with an alkali halide and/or hydrogen halide. ##STR2##

摘要翻译： 本发明涉及具有通式（I）和（II）的新己二醇，其中己糖醇骨架是杜尔醇醇，甘露糖醇或甘油，X代表卤素，优选溴，R是饱和或不饱和的C 4-10烷基羰基 其还含有游离的羧基，并且R 1是氢，也含有游离羧基，饱和或不饱和的C 2-10烷基羰基的饱和或不饱和C 4-10烷基羰基，饱和或不饱和的C 4-10烷基羰基， 还含有烷氧基羰基，或饱和或不饱和的C 8-10芳烷基羰基，以及这些化合物的盐。 根据本发明的新化合物具有肿瘤抑制作用。 根据本发明制备上述化合物，使得（a）通式（Ⅸ）的化合物，其中己糖醇骨架是二糖醇，甘露糖醇或甘露糖醇，Q是饱和或不饱和的C 11-17烷基羰基，其还含有 苄氧基羰基，Q 1为氢，饱和或不饱和的C 2-10烷基羰基，饱和或不饱和的还含有烷氧基羰基的C 4-10烷基羰基，也含有苄氧基羰基的饱和或不饱和C 11-17烷基羰基， 或饱和或不饱和的C 8-10芳烷基羰基在无影响环氧化物环的弱活性催化剂的存在下，在无水溶剂中氢化，或（b）一般的1,2-5,6-二脱水己糖醇 式（X）其中己糖醇骨架是杜尔醇醇，甘露糖醇或甘油，与通式（XI）的二羧酸酐反应，其中A是C 2-10烷基，芳烷基或芳基，或（c） 组合 和通式（I）的化合物与碱金属卤化物和/或卤化氢反应。

公开(公告)号：US4490378A

公开(公告)日：1984-12-25

申请号：US503791

申请日：1983-06-13

申请人： Lajos Dancsi ,  Tibor Keve ,  Gyorgy Fekete ,  Eszter Dezseri ,  Sandor Gorog ,  Tibor cs ,  Csaba Szantay ,  Lajos Szabo ,  Katalin Honty ,  Sandor Eckhardt ,  Ivan Hindi ,  Sandor Kerpel-Fronius ,  Zsuzsanna Relle nee Somfa ,  Janos Sugar

发明人： Lajos Dancsi ,  Tibor Keve ,  Gyorgy Fekete ,  Eszter Dezseri ,  Sandor Gorog ,  Tibor cs ,  Csaba Szantay ,  Lajos Szabo ,  Katalin Honty ,  Sandor Eckhardt ,  Ivan Hindi ,  Sandor Kerpel-Fronius ,  Zsuzsanna Relle nee Somfa ,  Janos Sugar

IPC分类号： A61K31/475 ,  A61P35/00 ,  C07D519/04

CPC分类号： C07D519/04 ,  Y10S514/908

摘要： The invention relates to new cytostatic compound, process for their preparation and pharmaceutical compositions containing them. More particularly, there are provided new compounds of the general formula ##STR1## in which R.sup.4 is .beta.-hydroxyl andR.sup.3 is .alpha.-ethyl; orR.sup.4 is hydrogen andR.sup.3 is .beta.-ethyl;R" is a straight chained alkyl having from 1 to 10 carbon atoms, or a branched chained alkyl having from 3 to 10 carbon atoms, in which groups the carbon atom attached to the >N.sub.a --CH.sub.2 --O-- group has a primary or secondary configuration or an alkenyl or alkinyl having from 3 to 6 carbon atoms, or an aralkyl having from 1 to 3 carbon atoms in the alkyl moiety;R.sup.1 is methoxy andR.sup.2 is acetyl, provided that if R.sup.3 is .alpha.-ethyl and R.sup.4 .beta.-hydroxyl,R.sup.4 is other than ethyl.These compounds and N-desmethyl-N-(ethoxymethyl)-vinblastine can be prepared according to the invention by transetherification of compounds of the compounds of the general formula ##STR2## with a large excess of alcohols of the general formulaR"--OH [III]Pharmaceutical compositions containing compounds of the general formula [I] as active ingredients are also within the scope of invention.

摘要翻译： 本发明涉及新的细胞生长抑制化合物，其制备方法和含有它们的药物组合物。 更具体地，提供了通式为“IMAGE”/ I /的新化合物，其中R 4是β-羟基和R 3是α-乙基; 或R4是氢，R3是β-乙基; R“是具有1至10个碳原子的直链烷基或具有3至10个碳原子的支链烷基，其中与> Na-CH 2 -O-基团连接的碳原子具有伯或 二级构型或具有3至6个碳原子的烯基或炔基，或在烷基部分具有1至3个碳原子的芳烷基; R1是甲氧基，R2是乙酰基，条件是如果R3是α-乙基和R4β-羟基，R4不是乙基。 这些化合物和N-去甲基-N-（乙氧基甲基） - 长春花碱可以根据本发明通过将通式为“IMAGE”/ II /的化合物的化合物与大量过量的通式R' '-OH [III]含有通式[I]化合物作为活性成分的药物组合物也在本发明的范围内。

公开(公告)号：US4410459A

公开(公告)日：1983-10-18

申请号：US293611

申请日：1981-08-17

申请人： Lajos Dancsi ,  Tibor Keve ,  Lajos Szabo ,  Katalin Honty ,  Sandor Eckhardt ,  Ivan Hindi ,  Sandor Kerpel-Fronius ,  Gyorgy Fekete ,  Eszter Dezseri ,  Sandor Gorog ,  Tibor Acs ,  Csaba Szantay ,  Zsuzsanna Relle nee Somfai ,  Janos Sugar

发明人： Lajos Dancsi ,  Tibor Keve ,  Lajos Szabo ,  Katalin Honty ,  Sandor Eckhardt ,  Ivan Hindi ,  Sandor Kerpel-Fronius ,  Gyorgy Fekete ,  Eszter Dezseri ,  Sandor Gorog ,  Tibor Acs ,  Csaba Szantay ,  Zsuzsanna Relle nee Somfai ,  Janos Sugar

IPC分类号： A61K31/475 ,  A61P35/00 ,  C07D519/04

CPC分类号： C07D519/04 ,  Y10S514/908

摘要： The invention relates to new cytostatic compound, process for their preparation and pharmaceutical compositions containing them. More particularly, there are provided new compounds of the general formula ##STR1## in which R.sup.4 is .beta.-hydroxyl andR.sup.3 is .alpha.-ethyl; orR.sup.4 is hydrogen andR.sup.3 is .beta.-ethyl;R" is a straight chained alkyl having from 1 to 10 carbon atoms, or a branched chained alkyl having from 3 to 10 carbon atoms, in which groups the carbon atom attached to the >N.sub.a -CH.sub.2 -O-- group has a primary or secondary configuration or an alkenyl or alkinyl having from 3 to 6 carbon atoms, or an aralkyl having from 1 to 3 carbon atoms in the alkyl moiety;R.sup.1 is methoxy andR.sup.2 is acetyl,provided that if R.sup.3 is .alpha.-ethyl and R.sup.4 .beta.-hydroxyl, R.sup.4 is other than ethyl.These compounds and N-desmethyl-N- ethoxy- methyl -vinblastine can be prepared according to the invention by transetherification of compounds of the compounds of the general formula ##STR2## with a large excess of alcohols of the general formulaR"--OH (III)Pharmaceutical compositions containing compounds of the general formula /I/ as active ingredients are also within the scope of invention.

摘要翻译： 本发明涉及新的细胞生长抑制化合物，其制备方法和含有它们的药物组合物。 更具体地，提供了通式为（I）的新化合物，其中R 4是β-羟基并且R 3是α-乙基; 或R4是氢，R3是β-乙基; R“是具有1至10个碳原子的直链烷基或具有3至10个碳原子的支链烷基，其中与> Na-CH 2 -O-基团连接的碳原子具有伯或 二级构型或具有3至6个碳原子的烯基或炔基，或在烷基部分具有1至3个碳原子的芳烷基; R1是甲氧基，R2是乙酰基，条件是如果R3是α-乙基和R4β-羟基，R4不是乙基。 这些化合物和N-去甲基-N-乙氧基 - 甲基 - 长春花碱可以根据本发明通过将通式为“IMAGE”（II）的化合物的化合物与大量过量的通式R' '-OH（III）含有通式I I化合物作为活性成分的药物组合物也在本发明的范围内。