公开(公告)号：US5608073A

公开(公告)日：1997-03-04

申请号：US673580

申请日：1996-07-01

申请人： Kenji Tsujihara ,  Tomiki Hashiyama ,  Motoaki Ohashi ,  Noriyuki Nakanishi

发明人： Kenji Tsujihara ,  Tomiki Hashiyama ,  Motoaki Ohashi ,  Noriyuki Nakanishi

IPC分类号： C07D263/04 ,  C07D263/06 ,  C07D305/14 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D413/12

CPC分类号： C07D263/04 ,  C07D263/06 ,  C07D305/14 ,  C07D405/12 ,  C07D407/12 ,  C07D409/12 ,  C07D413/12

摘要： A compound represented by the formula [I]: ##STR1## wherein R.sup.3 represents a lower alkanoyl group; R.sup.4 represents a substituted or unsubstituted benzoyl group; ring A represents a substituted or unsubstituted cyclopropane ring; X represents a single bond or a group represented by --O--,--S-- or --NH--, R represents a substituted or unsubstituted lower alkyl group (wherein said lower alkyl group may have a cycloalkyl moiety), a substituted or unsubstituted aryl group or a substituted or unsubstituted aromatic heterocyclic group; E represents hydrogen atom or a group represented by --CO(CH.sub.2).sub.n ZY; Y represents a residue obtained from an amino acid or a dipeptide by removing hydroxyl group in one carboxyl group therefrom (wherein amino group existing in said residue may be protected, and carboxyl group existing in said residue may be esterified or amidated); Z represents a group represented by the formula of --O-- or --NH--; and n represents 1, 2, 3, 4, 5 or 6, or a pharmaceutically acceptable salt thereof. Said compounds have excellent antitumor activity so that they are useful in the prophylaxis or treatment of a wide range of tumors such as breast cancer, ovary cancer, lung cancer, malignant melanoma and the like.

摘要翻译： 由式[I]表示的化合物：其中R 3表示低级烷酰基; R4表示取代或未取代的苯甲酰基; 环A表示取代或未取代的环丙烷环; X表示单键或由-O - ， - S-或-NH-表示的基团，R表示取代或未取代的低级烷基（其中所述低级烷基可具有环烷基部分），取代或未取代的芳基 或取代或未取代的芳族杂环基; E表示氢原子或由-CO（CH 2）n ZY表示的基团; Y表示通过从其中除去一个羧基中的羟基从氨基酸或二肽获得的残基（其中存在于所述残基中的氨基可被保护，并且所述残基中存在的羧基可被酯化或酰胺化）; Z表示由式-O-或-NH-表示的基团; 和n表示1,2,3,4,5或6或其药学上可接受的盐。 所述化合物具有优异的抗肿瘤活性，因此它们可用于预防或治疗广泛范围的肿瘤如乳腺癌，卵巢癌，肺癌，恶性黑素瘤等。

公开(公告)号：US06388078B1

公开(公告)日：2002-05-14

申请号：US09898007

申请日：2001-07-05

申请人： Takayuki Kawaguchi ,  Sumihiro Nomura ,  Kenji Tsujihara

发明人： Takayuki Kawaguchi ,  Sumihiro Nomura ,  Kenji Tsujihara

IPC分类号： C07D491147

CPC分类号： C07D491/14 ,  C07B2200/07 ,  C07D209/42 ,  C07D217/26

摘要： A camptothecin compound of the formula [XVIII]: wherein R4 is a lower alkanoyl group, R5 is an ethyl group, R7 is a —O(CH2)3NH2 group that may be protected by a —COOC(CH3)3 group, and R6, R8 and R9 are a hydrogen.

摘要翻译： 式[XVIII]的喜树碱化合物：其中R4是低级烷酰基，R5是乙基，R7是可被-COOC（CH3）3基团保护的-O（CH2）3NH2基团，R6是 R8和R9为氢。

公开(公告)号：US5837673A

公开(公告)日：1998-11-17

申请号：US689018

申请日：1996-07-30

申请人： Kenji Tsujihara ,  Takayuki Kawaguchi ,  Satoshi Okuno ,  Toshiro Yano

发明人： Kenji Tsujihara ,  Takayuki Kawaguchi ,  Satoshi Okuno ,  Toshiro Yano

IPC分类号： A61K9/00 ,  A61K31/4745 ,  A61K38/00 ,  A61K47/48 ,  A61P35/00 ,  C07D491/22 ,  C07K5/065 ,  C07K5/103 ,  C07K9/00 ,  A61K31/00 ,  A61K38/14

CPC分类号： C07D491/22 ,  A61K47/4823 ,  A61K47/48338 ,  C07K5/06078 ,  C07K5/1008 ,  C07K9/003 ,  A61K38/00

摘要： A camptothecin derivative comprising a compound of the formula �I!: ##STR1## wherein R.sup.1 is a substituted or unsubstituted lower alkyl group, X.sup.1 is a group of the formula: --NHR.sup.2 (R.sup.2 is a hydrogen atom or a lower alkyl group) or a group of --OH, and Alk is a straight chain or branched chain alkylene group having optionally an oxygen atom in the chain thereof, bound to a polysaccharide having carboxyl groups via an amino acid or a peptide, or a pharmaceutically acceptable salt thereof. Said camptothecin derivatives show enhanced antitumor activities but few side effects unlike conventional anticancer agents, and hence, these compounds are extremely useful as a medicament.

摘要翻译： 包含式[I]化合物的喜树碱衍生物：其中R1是取代或未取代的低级烷基，X1是下式的基团：-NHR2（R2是氢原子或低级烷基 基团）或一组-OH，Alk是其链中任选具有氧原子的直链或支链亚烷基，经由氨基酸或肽与具有羧基的多糖结合，或其药学上可接受的盐 其中。 所述喜树碱衍生物显示增强的抗肿瘤活性，但与常规抗癌剂不同​​的副作用很少，因此这些化合物作为药物是非常有用的。

公开(公告)号：US5650172A

公开(公告)日：1997-07-22

申请号：US479143

申请日：1995-06-07

申请人： Saburo Matsuda ,  Shigeyuki Ishikawa ,  Akira Suzuki ,  Kenji Tsujihara ,  Motoaki Ohashi

发明人： Saburo Matsuda ,  Shigeyuki Ishikawa ,  Akira Suzuki ,  Kenji Tsujihara ,  Motoaki Ohashi

IPC分类号： A61K9/107 ,  A61K9/14 ,  A61K9/19 ,  A61K47/12 ,  A61K47/18 ,  A61K47/26 ,  A61K9/10 ,  A61K9/16

CPC分类号： A61K9/14 ,  A61K9/1075 ,  A61K9/19 ,  Y10S514/937 ,  Y10S514/938

摘要： A preparation comprising a fat emulsion of fat microparticles wherein said emulsion contains a stabilizer consisting essentially of a fatty acid, a basic amino acid and a saccharide is provided. In the preparation comprising a fat emulsion of fat microparticles of the present invention, said microparticles having a mean particle diameter of at most 100 nm are stable, and so the microparticles remain in blood without being uptaken by liver. Therefore in case of administering a pharmaceutical preparation prepared by using the above-mentioned preparation of the present invention, the pharmacological activity may be expressed at a desired site. Thus the preparation is extremely useful as a drug carrier for drug delivery system. Furthermore, the pharmaceutical preparation of the present invention which is lyophilized can be easily and rapidly reconstituted into the pharmaceutical preparation comprising a fat emulsion of stable fat microparticles having a mean particle diameter of about at most 100 nm by adding distilled water, even after a long-term storage.

摘要翻译： 提供了包含脂肪微粒的脂肪乳液的制剂，其中所述乳液含有基本上由脂肪酸，碱性氨基酸和糖组成的稳定剂。 在包含本发明的脂肪微粒的脂肪乳剂的制剂中，平均粒径为100nm以下的微粒是稳定的，因此微粒保留在血液中而不被肝吸收。 因此，在施用通过使用本发明的上述制剂制备的药物的情况下，可以在期望的部位表达药理活性。 因此，该制剂作为药物递送系统的药物载体非常有用。 此外，冻干的本发明的药物制剂可以通过添加蒸馏水容易且迅速地重构成包含平均粒径为大约100nm的稳定脂肪微粒的脂肪乳剂的药物制剂，即使经过长时间 -term存储。

公开(公告)号：US5565569A

公开(公告)日：1996-10-15

申请号：US186016

申请日：1994-01-25

申请人： Kenji Tsujihara ,  Naoyuki Harada ,  Kunihiko Ozaki ,  Motoaki Ohashi ,  Koji Oda

发明人： Kenji Tsujihara ,  Naoyuki Harada ,  Kunihiko Ozaki ,  Motoaki Ohashi ,  Koji Oda

IPC分类号： C07D471/04 ,  A61K31/475

CPC分类号： C07D471/04

摘要： An ellipticine derivative of the formula [I]: ##STR1## wherein R is a substituted lower alkyl group, a substituted or unsubstituted lower alkoxy group or a heteromonocyclic group,or a pharmaceutically acceptable salt thereof, which show excellent antitumor activity, less side effects, less toxicity and/or high solubility in water and are useful as antitumor agent, and a process for preparing the same.

摘要翻译： 式[I]的玫瑰树碱衍生物：其中R是取代的低级烷基，取代或未取代的低级烷氧基或杂单环基或其药学上可接受的盐，其显示出优异的抗肿瘤活性， 较少的副作用，较少的毒性和/或在水中的高溶解性，并且可用作抗肿瘤剂，及其制备方法。

公开(公告)号：US4882447A

公开(公告)日：1989-11-21

申请号：US157969

申请日：1988-02-19

申请人： Kenji Tsujihara ,  Yoshihisa Arai ,  Osamu Ohtsuki ,  Tadashi Nakatani

发明人： Kenji Tsujihara ,  Yoshihisa Arai ,  Osamu Ohtsuki ,  Tadashi Nakatani

IPC分类号： C07F15/00

CPC分类号： C07F15/0093

摘要： Novel organic platinum complex of the formula: ##STR1## wherein R.sup.1 is hydrogen atom or a lower alkyl group, R.sup.2 is a substituted or unsubstituted lower alkyl group, a lower alkenyl group, a lower alkanoyl group, a mono- or di-lower alkylamino group, a substituted or unsubstituted nitrogen-containing hetero-monocyclic group, an oxygen-containing hetero-monocyclic group, or a group of the formula:--CH.sub.2 O(CH.sub.2 CH.sub.2 O).sub.m CH.sub.3, X is carbonyl group or sulfonyl group, m is an integer of 1 or 2,which has excellent anti-tumor activity against various tumors and is useful as an anti-tumor agent, and a process for the preparation thereof, and a pharmaceutical composition containing said compound.

公开(公告)号：US06512118B1

公开(公告)日：2003-01-28

申请号：US09227158

申请日：1999-01-08

申请人： Kenji Tsujihara ,  Takayuki Kawaguchi ,  Satoshi Okuno ,  Toshiro Yano

发明人： Kenji Tsujihara ,  Takayuki Kawaguchi ,  Satoshi Okuno ,  Toshiro Yano

IPC分类号： C07D47100

CPC分类号： C08B37/0018 ,  A61K47/61 ,  A61K47/65 ,  C08B37/0021

摘要： A camptothecin derivative comprising a compound of the formula [I] is disclosed: wherein R1, R2, R3, R4 and R5 are (A) adjacent two groups combine to form alkylene, or both are H, and one of the remaining three groups is —Xn-Alkm-R6, and the other two are H, alkyl or halogen, or (B) adjacent two groups combine to form alkylene, and one of the carbon atoms of said alkylene group is substituted by —Xn-Alkm-R6, and the remaining three groups are H, alkyl or a halogen, and one or two —CH2— of the alkylene in (A) or (B) may optionally be replaced by —O—, —S— or —NH—, X is —O— or —NH—, Alk is alkylene, R6 is —NH2, or —OH, m and n are both 0 or 1, or m is 1 and n is 0, which camptothecin compound is bound to a polysaccharide having carboxyl groups via an amino acid or a peptide, or a pharmaceutically acceptable salt thereof. Said camptothecin derivatives show enhanced antitumor activities but few side effects and are useful as a medicament.

摘要翻译： 公开了包含式[I]化合物的喜树碱衍生物：其中R1，R2，R3，R4和R5是（A）相邻的两个基团结合形成亚烷基，或两者都是H，其余三个基团之一是 -Xn-Alkm-R6，另外两个为H，烷基或卤素，或（B）相邻的两个基团结合形成亚烷基，所述亚烷基的一个碳原子被-Xn-Alkm-R6取代， 并且其余三个基团是H，烷基或卤素，并且（A）或（B）中亚烷基的一个或两个-CH 2可以任选地被-O - ， - S-或-NH-代替，X是 -O-或-NH-，Alk为亚烷基，R6为-NH2或-OH，m和n均为0或1，或m为1，n为0，喜树碱化合物与具有羧基的多糖结合 通过氨基酸或肽，或其药学上可接受的盐。 所述喜树碱衍生物显示出增强的抗肿瘤活性，但副作用很少，可用作药物。

公开(公告)号：US6015901A

公开(公告)日：2000-01-18

申请号：US172666

申请日：1998-10-15

申请人： Takayuki Kawaguchi ,  Sumihiro Nomura ,  Kenji Tsujihara

发明人： Takayuki Kawaguchi ,  Sumihiro Nomura ,  Kenji Tsujihara

IPC分类号： C07D487/04 ,  A61K31/436 ,  A61K31/4375 ,  C07D209/42 ,  C07D217/26 ,  C07D471/10 ,  C07D471/12 ,  C07D471/20 ,  C07D471/22 ,  C07D491/14 ,  C07D491/147 ,  C07D491/20 ,  C07D491/22 ,  C07D471/14

CPC分类号： C07D491/14 ,  C07D209/42 ,  C07D217/26 ,  C07B2200/07

摘要： A process for preparing S type 2-substituted hydroxy-2-indolidinyl-butyric ester compound [II]: ##STR1## wherein R.sup.0 is residue of nitrogen-containing fused heterocyclic carboxylic acid having absolute configuration of "R"(in which the nitrogen atom is protected), R.sup.1 and R.sup.2 are lower alkyl group, and E is ester residue, which is useful as an intermediate for preparing camptothecin derivatives having antitumor activities, which comprises 2-ethylating 2-substituted hydroxy-2-indolidinylacetic ester compound [I]: ##STR2## wherein the symbols are as defined above.

摘要翻译： 一种制备S型2-取代羟基-2-吲哚哩啶基 - 丁酸酯化合物[II]的方法：其中R 0是具有绝对构型“R”（其中保护氮原子）的含氮稠合杂环羧酸的残基， R 1和R 2为低级烷基，E为酯残基，其可用作制备具有抗肿瘤活性的喜树碱衍生物的中间体，其包括2-乙基化2-取代的羟基-2-吲哚哩啶基乙酸酯化合物[I]：其中 符号如上所述。

公开(公告)号：US5605904A

公开(公告)日：1997-02-25

申请号：US449273

申请日：1995-05-24

申请人： Kenji Tsujihara ,  Naoyuki Harada ,  Kunihiko Ozaki ,  Motoaki Ohashi ,  Koji Oda

发明人： Kenji Tsujihara ,  Naoyuki Harada ,  Kunihiko Ozaki ,  Motoaki Ohashi ,  Koji Oda

IPC分类号： C07D471/04 ,  A61K31/435

CPC分类号： C07D471/04

摘要： An ellipticine derivative of the formula [I]: ##STR1## wherein R is a substituted lower alkyl group, a substituted or unsubstituted lower alkoxy group or a heteromonocyclic group, or a pharmaceutically acceptable salt thereof, which show excellent antitumor activity, less side effects, less toxicity and/or high solubility in water and are useful as antitumor agent, and a process for preparing the same.

摘要翻译： 式[I]的玫瑰树碱衍生物：其中R是取代的低级烷基，取代或未取代的低级烷氧基或杂单环基或其药学上可接受的盐，其显示出优异的抗肿瘤活性， 较少的副作用，较少的毒性和/或在水中的高溶解性，并且可用作抗肿瘤剂，及其制备方法。

公开(公告)号：US4886894A

公开(公告)日：1989-12-12

申请号：US164489

申请日：1988-03-04

申请人： Kenji Tsujihara ,  Yoshihisa Arai ,  Osamu Ohtsuki ,  Tadashi Nakatani

发明人： Kenji Tsujihara ,  Yoshihisa Arai ,  Osamu Ohtsuki ,  Tadashi Nakatani

IPC分类号： A61K38/00 ,  C07F15/00 ,  C07K5/06 ,  C07K5/08

CPC分类号： C07F15/0093 ,  C07K5/06191 ,  C07K5/0827 ,  A61K38/00

摘要： Novel organic platinum complex of the formula: ##STR1## wherein R.sup.1 is hydrogen atom or a lower alkyl group; R.sup.2 is hydrogen atom, a substituted or unsubstituted lower alkyl group, a lower alkenyl group, a lower alkynyl agroup, a lower alkoxy group, a lower alkanoyl group, amino group, a substituted or unsubstituted nitrogen-containing hetero-monocyclic group, or an oxygen-containing hetero-monocyclic group, Alk is a lower alkylene group, X is carbonyl or sulfonyl group, n is 1 or 2, which has excellent anti-tumor activity against various tumors and is useful as an anti-tumor agent, and a process for the preparation thereof, and a pharmaceutical composition containing said compound.