公开(公告)号：EP1710244A1

公开(公告)日：2006-10-11

申请号：EP05704397.8

申请日：2005-01-28

申请人： Eisai R&D Management Co., Ltd. ,  MERCIAN CORPORATION

发明人： ISHIHARA, Hiroshi ,  TAKEDA, Susumu ,  YAMADA, Tomonari ,  ASAHI, Yoshiaki

IPC分类号： C07D407/06 ,  C07D313/00 ,  C12P17/08 ,  C08B37/16

CPC分类号： C12N1/20 ,  C07D313/00 ,  C12P17/162

摘要： The present invention provides a method for stabilizing a macrolide compound, and an efficient method for producing the compound. Specifically, it provides a method for stabilizing a macrolide compound, in which a 12-membered ring macrolide compound, such as a compound expressed by the formula (1) and a cyclodextrin are both present, and a method for producing a macrolide compound, in which a cyclodextrin is made to be present in a culture broth of actinomycetes having an ability of producing the macrolide compound.

摘要翻译： 本发明提供了一种稳定大环内酯类化合物的方法和一种制备该化合物的有效方法。 具体地说，本发明提供了稳定大环内酯类化合物的方法，其中存在12元环大环内酯化合物，例如式（1）表示的化合物和环糊精两者，以及大环内酯类化合物的制备方法， 使得环糊精存在于具有产生大环内酯化合物的能力的放线菌的培养液中。

公开(公告)号：EP1770165B1

公开(公告)日：2011-12-21

申请号：EP05766205.8

申请日：2005-07-19

申请人： Eisai R&D Management Co., Ltd. ,  MERCIAN CORPORATION

发明人： MACHIDA, Kazuhiro ,  ARISAWA, Akira ,  TAKEDA, Susumu ,  YOSHIDA, Masashi ,  TSUCHIDA, Toshio

IPC分类号： C12N15/52 ,  C07K14/36 ,  C12N9/00 ,  C12N9/02 ,  C12P17/16 ,  C12P17/08

CPC分类号： C12P17/08 ,  C07K14/36 ,  C12N9/0071 ,  C12N9/0073 ,  C12N15/52 ,  C12P17/162

摘要： A polypeptide participating in the biosynthesis of pladienolide as a macrolide compound; a DNA coding for such a polypeptide; a variant thereof; a transformant in which part or the whole of such a DNA or variant thereof has been incorporated; and a process for producing pladienolide as a macrolide compound with the use of such a transformant. In particular, there is provided an isolated pure DNA comprising at least one region coding for a polypeptide participating in the biosynthesis of pladienolide. Further, there are provided a polypeptide coded for by this DNA and a recombinant plasmid capable of self-replication or integration replication carrying this DNA. Still further, there are provided a transformant carrying this DNA and a process for producing pladienolide, characterized in that this transformant is cultured in a culture medium and pladienolide is collected from the culture solution.

公开(公告)号：EP1770165A1

公开(公告)日：2007-04-04

申请号：EP05766205.8

申请日：2005-07-19

申请人： Eisai R&D Management Co., Ltd. ,  MERCIAN CORPORATION

发明人： MACHIDA, Kazuhiro ,  ARISAWA, Akira ,  TAKEDA, Susumu ,  YOSHIDA, Masashi ,  TSUCHIDA, Toshio

IPC分类号： C12N15/52 ,  C07K14/36 ,  C12N1/15 ,  C12N1/19 ,  C12N1/21 ,  C12N5/10 ,  C12N9/00 ,  C12N9/02 ,  C12P17/16

CPC分类号： C12P17/08 ,  C07K14/36 ,  C12N9/0071 ,  C12N9/0073 ,  C12N15/52 ,  C12P17/162

摘要： The present invention provides polypeptides that participate in the biosynthesis of the pladienolide macrolide compounds, DNA that encodes these polypeptides and variants of this DNA, transformants that maintain all or a portion of this DNA or variant thereof, and a method of producing the pladienolide macrolide compounds using these transformants. More particularly, it provides an isolated pure DNA that contains at least one region encoding a polypeptide that participates in pladienolide biosynthesis; polypeptide encoded by this DNA; a self-replicating or integrated-replicating recombinant plasmid carrying this DNA; a transformant maintaining this DNA; and a method of producing a pladienolide, characterized by culturing this transformant on culture medium and collecting pladienolide from this culture medium.

摘要翻译： 本发明提供了参与扁桃苷内酰胺大环内酯化合物的生物合成的多肽，编码这些多肽的DNA和该DNA的变体，保持该DNA或其变体的全部或一部分的转化体，以及生产该扁桃苷内酰胺大环内酯化合物的方法 使用这些转化体。 更具体地，其提供了分离的纯DNA，其含有至少一个编码参与泛二烯内酯生物合成的多肽的区域; 由该DNA编码的多肽; 携带该DNA的自复制或整合复制重组质粒; 维持该DNA的转化体; 以及生产普拉二烯内酯的方法，其特征在于在培养基上培养该转化体并从该培养基中收集普拉地奈内酯。

公开(公告)号：EP1548121B1

公开(公告)日：2015-04-29

申请号：EP03771459.9

申请日：2003-07-31

申请人： Eisai R&D Management Co., Ltd.

发明人： KOTAKE, Yoshihiko ,  NIIJIMA, Jun ,  FUKUDA, Yoshio ,  NAGAI, Mitsuo ,  KANADA, Regina Mikie ,  TAKEDA, Susumu ,  NAKASHIMA, Takashi ,  YOSHIDA, Masashi ,  TSUCHIDA, Toshio ,  SAMESHIMA, Tomohiro

IPC分类号： C07D407/06 ,  C07D313/00 ,  C12P17/16 ,  C12P17/08

CPC分类号： C07D407/06 ,  C07D313/00 ,  C12P17/08 ,  C12P17/16 ,  C12P17/162

公开(公告)号：EP1548121A1

公开(公告)日：2005-06-29

申请号：EP03771459.9

申请日：2003-07-31

申请人： MERCIAN CORPORATION ,  Eisai Co., Ltd.

发明人： KOTAKE, Yoshihiko ,  NIIJIMA, Jun ,  FUKUDA, Yoshio ,  NAGAI, Mitsuo ,  KANADA, Regina Mikie ,  TAKEDA, Susumu ,  NAKASHIMA, Takashi ,  YOSHIDA, Masashi ,  TSUCHIDA, Toshio ,  SAMESHIMA, Tomohiro

IPC分类号： C12P17/16

CPC分类号： C07D407/06 ,  C07D313/00 ,  C12P17/08 ,  C12P17/16 ,  C12P17/162

摘要： Compounds represented by the following general formula (I), pharmacologically acceptable salts thereof or hydrates of the same: (I) wherein W represents
and R 3 , R 7 , R 16 , R 17 , R 20 , R 21 and R 21' are the same or different and each represents hydrogen, etc. Because of inhibiting angiogenesis and inhibiting the production of VEGF particularly in hypoxia, the compounds (I) are useful as remedies for solid cancer.

摘要翻译： 由以下通式（I）表示的化合物，其药理学上可接受的盐或其水合物：其中W表示和R 3，R 7，R 16，R 17， R 20，R 21和R 21'均相同或不同，各自表示氢等。由于抑制血管发生并抑制VEGF的产生，特别是在缺氧中，化合物（I）可用作 固体癌治疗。

公开(公告)号：EP1580278A1

公开(公告)日：2005-09-28

申请号：EP03775924.8

申请日：2003-11-27

申请人： MERCIAN CORPORATION ,  Eisai Co., Ltd.

发明人： OKUDA, Akifumi ,  YAMAMOTO, Satoshi ,  SAKAI, Takashi ,  TAKEDA, Susumu ,  NAKASHIMA, Takashi ,  KANEKO, Katsura ,  SAMESHIMA, Tomohiro ,  KATO, Taira ,  KAWAMURA, Naoto

IPC分类号： C12P17/16 ,  C07D407/06 ,  C12N1/20 ,  A61P35/00 ,  A61K31/336

CPC分类号： C07D407/06 ,  A61K31/336 ,  C12P17/162

摘要： The present invention provides a novel method of producing the 12-membered ring macrolide compound 11107D having an antitumor activity by biological transformation. Starting material which is the 12-membered ringmacrolide compound 11107B represented by the formula (I) is incubated in the presence of a strain belonging to the genus Mortierella, the genus Streptomyces or the family Micromonosporaceae (for example, Streptomyces sp. AB-1704 strain (FERM BP-8551)), each of which has the ability of transforming the 12-membered ring macrolide compound 11107B into a 11107D substance represented by the formula (II), or a preparation of its cultured mycelia and oxygen, and then 11107D substance which is a target material is collected from the treating solution.

摘要翻译： 本发明提供了一种通过生物转化生产具有抗肿瘤活性的12元环大环内酯化合物11107D的新方法。 在属于被孢霉属，链霉菌属或小单孢菌科（例如链霉菌属AB-1704菌株）的菌株存在下，将由式（I）表示的12-元环大环内酯化合物11107B （FERM BP-8551）），它们各自具有将12元环大环内酯化合物11107B转化为由式（II）表示的11107D物质或其培养的菌丝体和氧的制剂的能力，然后将11107D物质 从处理溶液中收集作为目标物质的物质。

公开(公告)号：EP1380579A1

公开(公告)日：2004-01-14

申请号：EP02711280.4

申请日：2002-02-01

申请人： MERCIAN CORPORATION ,  Eisai Co., Ltd.

发明人： MIZUI, Yoshiharu ,  SAKAI, Takashi ,  YAMAMOTO, Satoshi ,  KOMEDA, Keisuke ,  FUJITA, Masanori ,  OKUDA, Akifumi ,  KISHI, Kumiko ,  NIIJIMA, Jun ,  NAGAI, Mitsuo ,  OKAMOTO, Kiyoshi ,  IWATA, Masao ,  KOTAKE, Yoshihiko ,  UENAKA, Toshimitsu ,  ASAI, Naoki ,  MATSUFUJI, Motoko ,  SAMESHIMA, Tomohiro ,  KAWAMURA, Naoto ,  DOBASHI, Kazuyuki ,  NAKASHIMA, Takashi ,  YOSHIDA, Masashi ,  TSUCHIDA, Toshio ,  TAKEDA, Susumu ,  YAMADA, Tomonari ,  NORIHISA, Koji ,  YAMORI, Takao

IPC分类号： C07D313/00 ,  C07D405/14 ,  C07D407/06 ,  C07D493/10 ,  C07D493/04 ,  A61K31/335 ,  A61K31/336 ,  A61K31/4427 ,  A61K31/4523 ,  A61K31/455 ,  A61K31/4025 ,  A61K31/5377 ,  A61K31/496 ,  A61K31/74 ,  A61P43/00 ,  A61P7/00 ,  A61P35/00 ,  A61P35/04 ,  A61P29/00 ,  A61P19/02 ,  A61P27/02

CPC分类号： C07D405/14 ,  A61K31/335 ,  A61K31/336 ,  A61K31/4025 ,  A61K31/4427 ,  A61K31/4523 ,  A61K31/455 ,  A61K31/496 ,  A61K31/5377 ,  A61K31/74 ,  C07D313/00 ,  C07D407/06 ,  C07D407/14 ,  C07D493/04 ,  C07D493/08 ,  C12P17/02

摘要： The presentinvention provides a novel bioactive substance having an antitumor activity and a process for producing it, and a medical use thereof. Namely, it provides a 12-membered ring macrolide compound represented by the following formula obtained from the incubation solution of Streptomyces sp. Mer. 11107 or a variant thereof, a pharmacologically acceptable salt thereof or a hydrate of them, and a process for producing it.

摘要翻译： 本发明提供了具有抗肿瘤活性的新型生物活性物质及其生产方法及其医疗用途。 也就是说，提供了由链霉菌（Streptomyces sp。）培养溶液得到的下式所示的12元环大环内酯化合物。 Mer的。 11107或其变体，其药理学上可接受的盐或它们的水合物及其制备方法。