公开(公告)号：US6118011A

公开(公告)日：2000-09-12

申请号：US753650

申请日：1996-11-27

申请人： Eric Mayhew ,  J. Craig Franklin ,  Suresh Bhatia ,  Paul A. Harmon ,  Andrew S. Janoff

发明人： Eric Mayhew ,  J. Craig Franklin ,  Suresh Bhatia ,  Paul A. Harmon ,  Andrew S. Janoff

IPC分类号： A61K9/127 ,  A61K31/335 ,  A61K31/337 ,  A61K31/66 ,  A61P35/00 ,  C07D305/14 ,  C07F9/655

CPC分类号： B82Y5/00 ,  A61K9/127 ,  C07D305/14 ,  C07F9/65512

摘要： This invention provides a taxane derivative of the formula: ##STR1## wherein a hydrophobic organic moiety is attached to a taxane. R and R.sup.1 is each indepently H or a hydrophobic organic moiety, as long as at least one of R and R.sup.1 is not H. Attachment of a hydrophobic organic moiety to the taxane so as to obtain a taxane derivative generally stabilizes the association of the derivative with a lipid, including a liposomal lipid, carrier in the plasma of animals to which the derivative-carrier association is administered. Also provided herein is a composition containing the taxane derivative and a pharmaceutically acceptable medium; desirably, the medium also contains a lipid carrier, and the derivative is associated with the carrier. Further provided herein is a method of administering taxane derivatives to animals, for example, animals afflicted with cancers.

摘要翻译： 本发明提供下式的紫杉烷衍生物：其中疏水性有机部分连接于紫杉烷。 R和R 1各自独立地为H或疏水性有机部分，只要R和R 1中的至少一个不为H.将疏水性有机部分连接到紫杉烷以获得紫杉烷衍生物通常稳定该衍生物的缔合 其中包含脂质体脂质的脂质，其中施用衍生物 - 载体缔合的动物血浆中的载体。 本文还提供含有紫杉烷衍生物和药学上可接受的介质的组合物; 理想地，培养基还含有脂质载体，并且该衍生物与载体相关联。 本文还提供了将紫杉烷衍生物施用于动物，例如患有癌症的动物的方法。

公开(公告)号：US6107332A

公开(公告)日：2000-08-22

申请号：US249004

申请日：1999-02-12

申请人： Shaukat Ali ,  J. Craig Franklin ,  Imran Ahmad ,  Eric Mayhew ,  Soumendu Bhattacharya ,  Gil Koehane ,  Andrew S. Janoff

发明人： Shaukat Ali ,  J. Craig Franklin ,  Imran Ahmad ,  Eric Mayhew ,  Soumendu Bhattacharya ,  Gil Koehane ,  Andrew S. Janoff

IPC分类号： A61K9/127 ,  A61P35/00 ,  C07D305/14 ,  A61K31/337

CPC分类号： C07D305/14 ,  A61K9/127

摘要： Provided herein is a taxane having a hydrocarbon attached at the 2' and/or 7 positions, the hydrocarbon's alpha position being occupied by a "hydrolysis-promoting group" ("HPG"). In one embodiment, the hydrolysis promoting group is stereospecifically attached to the .alpha.-carbon of the hydrophobic taxane. The Substitution of an HPG for the methylene unit ordinarily occupying the alpha position allows for enhanced in vivo hydrolysis of the hydrocarbon-taxane bond, and hence, for enhanced taxane therapeutic activity. Also provided herein are taxane-containing compositions, and methods of administering taxanes to animals, including those afflicted with cancers or inflammatory diseases.

摘要翻译： 本文提供了具有在2'和/或7位上连接的烃的紫杉烷，烃的α位置被“水解促进基团”（“HPG”）占据。 在一个实施方案中，水解促进基团立体特异性地连接到疏水紫杉烷的α-碳上。 通常占据α位置的通常占据α位置的亚甲基单元的HPG的取代允许烃 - 紫杉烷键的体内水解增强，因此增强紫杉烷治疗活性。 本文还提供了含紫杉烷的组合物，以及向动物（包括患有癌症或炎性疾病的患者）施用紫杉烷的方法。

公开(公告)号：US5939567A

公开(公告)日：1999-08-17

申请号：US988120

申请日：1997-12-10

申请人： Eric Mayhew ,  J. Craig Franklin ,  Suresh Bhatia ,  Paul A. Harmon ,  Andrew S. Janoff

发明人： Eric Mayhew ,  J. Craig Franklin ,  Suresh Bhatia ,  Paul A. Harmon ,  Andrew S. Janoff

IPC分类号： A61K9/127 ,  A61K31/335 ,  A61K31/337 ,  A61K31/66 ,  A61P35/00 ,  C07D305/14 ,  C07F9/655

CPC分类号： B82Y5/00 ,  A61K9/127 ,  C07D305/14 ,  C07F9/65512

摘要： This invention provides a taxane derivative of the formula: ##STR1## wherein a hydrophobic organic moiety is attached to a taxane. R and R.sup.1 is each indepently H or a hydrophobic organic moiety, as long as at least one of R and R.sup.1 is not H. Attachment of a hydrophobic organic moiety to the taxane so as to obtain a taxane derivative generally stabilizes the association of the derivative with a lipid, including a liposomal lipid, carrier in the plasma of animals to which the derivative-carrier association is administered. Also provided herein is a composition containing the taxane derivative and a pharmaceutically acceptable medium; desirably, the medium also contains a lipid carrier, and the derivative is associated with the carrier. Further provided herein is a method of administering taxane derivatives to animals, for example, animals afflicted with cancers.

摘要翻译： 本发明提供下式的紫杉烷衍生物：其中疏水性有机部分连接于紫杉烷。 R和R 1各自独立地为H或疏水性有机部分，只要R和R 1中的至少一个不为H.将疏水性有机部分连接到紫杉烷以获得紫杉烷衍生物通常稳定该衍生物的缔合 其中包含脂质体脂质的脂质，其中施用衍生物 - 载体缔合的动物血浆中的载体。 本文还提供含有紫杉烷衍生物和药学上可接受的介质的组合物; 理想地，培养基还含有脂质载体，并且该衍生物与载体相关联。 本文还提供了将紫杉烷衍生物施用于动物，例如患有癌症的动物的方法。