公开(公告)号：US5466677A

公开(公告)日：1995-11-14

申请号：US204020

申请日：1994-02-28

申请人： Anthony D. Baxter ,  Eric K. Baylis ,  Stephen P. Collingwood ,  Roger J. Taylor ,  Alain De Mesmaeker ,  Chantal Schmit

发明人： Anthony D. Baxter ,  Eric K. Baylis ,  Stephen P. Collingwood ,  Roger J. Taylor ,  Alain De Mesmaeker ,  Chantal Schmit

IPC分类号： G01N33/569 ,  A61K31/665 ,  A61K31/70 ,  A61K31/7042 ,  A61K31/7052 ,  A61K31/7064 ,  A61K31/7072 ,  A61K31/7076 ,  A61P31/12 ,  A61P31/16 ,  C07F9/6512 ,  C07F9/655 ,  C07F9/6561 ,  C07H19/04 ,  C07H19/06 ,  C07H19/16 ,  C07H21/00 ,  C07H21/02 ,  C07H21/04

CPC分类号： C07H21/00 ,  C07H19/04

摘要： A dinucleotide analogue of formula ##STR1## where B.sup.1 and B.sup.2 are each independently a monovalent nucleoside base radical;R.sup.1 is R.sup.1.sub.a or Z;R.sup.1.sub.a, R.sup.2, R.sup.3 and R.sup.4 are each independently hydrogen, halogen or hydroxy;R.sup.5 is R.sup.5.sub.a or Z;R.sup.6 is hydrogen or R.sup.6.sub.a ;R.sup.7 is hydrogen, alkyl-N,N-dialkylphosphoramidyl or R.sup.7.sub.a, R.sup.8 is R.sup.8.sub.a or Z, or the indicated R.sup.7 O and R.sup.8 together denote an isopropylidenedioxy group;R.sup.5.sub.a and R.sup.8.sub.a are each independently hydrogen, halogen, hydroxy, --OR.sup.10, --OCOR.sup.10 or silyloxy substituted by three C.sub.1 -C.sub.15 hydrocarbyl groups;R.sup.6.sub.a and R.sup.7.sub.a are each independently a C.sub.1 -C.sub.10 aliphatic radical, a C.sub.6 -C.sub.15 aromatic radical, a C.sub.7 -C.sub.30 araliphatic radical, --COR.sup.11, --SO.sub.2 R.sup.11 or silyl substituted by three C.sub.1 -C.sub.15 hydrocarbyl groups;R.sup.9 is hydrogen, a C.sub.1 -C.sub.8 aliphatic radical, a C.sub.3 -C.sub.8 cycloaliphatic radical, a C.sub.6 -C.sub.15 aromatic radical, a C.sub.7 -C.sub.13 araliphatic radical, an alkali metal ion or an ammonium ion;R.sup.10 and R.sup.11 are each independently a C.sub.1 -C.sub.10 aliphatic radical, a C.sub.3 -C.sub.8 cycloaliphatic radical, a C.sub.6 -C.sub.15 aromatic radical or a C.sub.7 -C.sub.16 araliphatic radical;R.sup.x and R.sup.y are independently hydrogen, halogen, hydroxy, a C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.6 -C.sub.15 aryl, C.sub.7 -C.sub.16 aralkyl, C.sub.1 -C.sub.10 alkoxy, C.sub.2 -C.sub.10 alkenoxy, C.sub.6 -C.sub.10 aryloxy or C.sub.7 -C.sub.16 aralkyloxy group, which is substituted or unsubstituted, or --OCOR.sup.z ;R.sup.z is a substituted or unsubstituted C.sub.1 -C.sub.10 alkyl, C.sub.2 -C.sub.10 alkenyl, C.sub.3 -C.sub.8 cycloalkyl, C.sub.6 -C.sub.15 aryl or C.sub.7 -C.sub.16 aralkyl group; andZ is C.sub.6 -C.sub.10 aryloxythiocarbonyloxy, the C.sub.6 -C.sub.10 aryl group being substituted or unsubstituted.

摘要翻译： 式Ⅰ的二核苷酸类似物，其中B1和B2各自独立地是一价核苷碱基; R1为R1a或Z; R1a，R2，R3和R4各自独立地为氢，卤素或羟基; R5为R5a或Z; R6是氢或R6a; R7是氢，烷​​基-N，N-二烷基磷酰胺基或R7a，R8是R8a或Z，或者所指示的R7O和R8一起表示异丙烯二氧基; R5a和R8a各自独立地为氢，卤素，羟基，-OR10，-OCOR10或被三个C1-C15烃基取代的甲硅烷氧基; R6a和R7a各自独立地为C1-C10脂族基团，C6-C15芳族基团，C7-C30芳脂族基团，-COR11，-SO2R11或被三个C1-C15烃基取代的甲硅烷基基团; R9是氢，C1-C8脂族基团，C3-C8脂环族基团，C6-C15芳族基团，C7-C13芳脂族基团，碱金属离子或铵离子; R 10和R 11各自独立地为C 1 -C 10脂族基团，C 3 -C 8脂环族基团，C 6 -C 15芳族基团或C 7 -C 16芳脂族基团; Rx和Ry独立地是氢，卤素，羟基，C1-C10烷基，C2-C10烯基，C3-C8环烷基，C6-C15芳基，C7-C16芳烷基，C1-C10烷氧基，C2-C10链烯氧基，C6-C10芳氧基 或取代或未取代的C 7 -C 16芳烷氧基或-OCOR z; Rz是取代或未取代的C1-C10烷基，C2-C10烯基，C3-C8环烷基，C6-C15芳基或C7-C16芳烷基; Z为C6-C10芳氧基硫代羰氧基，C6-C10芳基为取代或未取代的。

公开(公告)号：US5508270A

公开(公告)日：1996-04-16

申请号：US203962

申请日：1994-02-28

申请人： Anthony D. Baxter ,  Eric K. Baylis ,  Stephen P. Collingwood ,  Roger J. Taylor ,  Alain Mesmaeker ,  Chantal Schmit

发明人： Anthony D. Baxter ,  Eric K. Baylis ,  Stephen P. Collingwood ,  Roger J. Taylor ,  Alain Mesmaeker ,  Chantal Schmit

IPC分类号： C07H9/04 ,  C07F9/30 ,  C07H13/06 ,  C07H19/06 ,  C07H19/10 ,  C07H19/16 ,  C07H19/20 ,  C07H21/00 ,  A61K31/70

CPC分类号： C07H19/10 ,  C07H19/20 ,  C07H21/00 ,  Y02P20/55

摘要： A compound of formula ##STR1## where R.sup.1 is hydrogen or a protecting group Q;R.sup.2 is hydrogen, a C.sub.1 -C.sub.8 aliphatic radical, a C.sub.6 -C.sub.15 aromatic radical, a C.sub.3 -C.sub.8 cycloaliphatic radical, a C.sub.7 -C.sub.13 araliphatic radical, an alkali metal ion or an ammonium ion;R.sup.3 and R.sup.4 are independently hydrogen, halogen or hydroxy;R.sup.5 is C.sub.6 -C.sub.10 aryloxythiocarbonyloxy, the C.sub.6 -C.sub.10 aryl group being unsubstituted or substituted, or R.sup.5.sub.a ;R.sup.5.sub.a is hydrogen, fluorine, chlorine, hydroxy, --OR.sup.8, --OCOR.sup.8 or silyloxy substituted by three C.sub.1 -C.sub.15 hydrocarbyl groups;R.sup.6 is hydrogen, a C.sub.1 -C.sub.10 aliphatic radical, a C.sub.6 -C.sub.15 aromatic radical, a C.sub.7 -C.sub.16 araliphatic radical, --COR.sup.9, --SO.sub.2 R.sup.9 or silyl substituted by three C.sub.1 -C.sub.15 hydrocarbyl groups;R.sup.7 is a monovalent nucleoside base radical, hydroxyl, --OR.sup.8 or --OCOR.sup.8, andR.sup.9 are independently a C.sub.1 -C.sub.10 aliphatic radical, a C.sub.3 -C.sub.8 cycloaliphatic radical, a C.sub.6 -C.sub.15 aromatic radical or a C.sub.7 -C.sub.16 araliphatic radical; orR.sup.5 and the indicated R.sup.6 O-together denote an isopropylidenedioxy group or R.sup.5 and R.sup.7 together denote an isopropylidenedioxy group, provided that when R.sup.5 and R.sup.7 together denote isopropylidenedioxy, R.sup.1 R.sup.2, R.sup.3 R.sup.4 and R.sup.6 are not all hydrogen. The disclosure further relates to a method of preparing the compounds of formula I by reacting a olefinic acetonide with a phosphinate compound and to the use of the compounds of formula I as pharmaceutical agents.

摘要翻译： 式Ⅰ的化合物，其中R 1是氢或保护基团Q; R2是氢，C1-C8脂族基团，C6-C15芳族基团，C3-C8脂环族基团，C7-C13芳脂族基团，碱金属离子或铵离子; R3和R4独立地是氢，卤素或羟基; R5是C6-C10芳氧基硫代羰氧基，C6-C10芳基是未取代或取代的，或R5a; R5a是氢，氟，氯，羟基，-OR8，-OCOR8或被三个C1-C15烃基取代的甲硅烷氧基; R 6是氢，C 1 -C 10脂族基，C 6 -C 15芳基，C 7 -C 16芳脂基，-COR 9，-SO 2 R 9或被三个C 1 -C 15烃基取代的甲硅烷基; R7是单价核苷碱基，羟基-OR8或-OCOR8，R9独立地是C1-C10脂族基团，C3-C8脂环族基团，C6-C15芳族基团或C7-C16芳脂族基团; 或R5和所示的R6O一起表示异丙烯二氧基，或者R 5和R 7一起表示异亚丙二氧基，条件是当R 5和R 7一起表示异亚丙二氧基时，R 1 R 2，R 3 R 4和R 6不全为氢。 本公开还涉及通过使烯属丙烯腈与次膦酸盐化合物反应制备式I化合物的方法，以及式I化合物作为药剂的用途。