公开(公告)号：US06228391B1

公开(公告)日：2001-05-08

申请号：US09202193

申请日：1998-12-10

Applicant: Kazuhiro Shimizu ,  Masashi Isozaki ,  Kazunori Koiwai

Inventor： Kazuhiro Shimizu ,  Masashi Isozaki ,  Kazunori Koiwai

IPC: C07C25714

CPC classification number: C07C257/18 ,  A61K9/1272 ,  C07C257/14 ,  C07C335/32 ,  C07C335/36

Abstract: Novel amidine derivatives of the formula (1); and drug carriers such as liposomes or emulsions comprising the derivatives, which can enclose genetic materials or drugs and transfer them to cells or affected sites efficiently and safely, wherein A is an aromatic ring, R1 and R2 are the same or different and independently represent an alkyl group having any one of 10 to 25 carbon atoms, and an alkenyl group having any one of 10 to 25 carbon atoms, X and Y are the same or different and independently represent —O—, —S—, —COO—, —OCO—, —CONH—, or —NHCO—, m is 0 or 1, and n is 0 or a natural number of 1 to 6.

Abstract translation: 式（1）的新型脒衍生物; 和药物载体如脂质体或包含衍生物的乳剂，其可以包裹遗传材料或药物并且有效和安全地将它们转移到细胞或受影响的位点，其中A是芳环，R 1和R 2相同或不同并且独立地表示 具有10至25个碳原子的任何一个的烷基和具有10至25个碳原子的任何一个的烯基可以相同或不同并且独立地表示-O - ， - S - ， - COO - ， - OCO-，-CONH-或-NHCO-，m为0或1，n为0或自然数为1至6。

公开(公告)号：US20080146796A1

公开(公告)日：2008-06-19

申请号：US11984988

申请日：2007-11-26

Applicant: Tetsuro Kawanishi ,  Masashi Isozaki

Inventor： Tetsuro Kawanishi ,  Masashi Isozaki

IPC: C07D487/14

CPC classification number: C07D498/18 ,  B01D15/322 ,  B01D15/325

Abstract: A process for preparing an o-alkylated rapamycin derivative represented by the following general formula (1) is provided. The process includes the steps of reacting rapamycin with an alkyl triflate, purifying the resulting reaction product with a normal phase chromatograph and further purifying a purified product, which has been purified with the normal phase chromatograph, with a reverse phase chromatography wherein R represents an alkyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, acyloxyalkyl, aminoalkyl, alkylaminoalkyl, alkoxycarbonylaminoalkyl, acylaminoalkyl, or aryl.

Abstract translation: 提供了制备由以下通式（1）表示的邻烷基化的雷帕霉素衍生物的方法。 该方法包括以下步骤：使雷帕霉素与三氟甲磺酸烷基酯反应，用正相色谱法纯化所得反应产物，并进一步纯化已经用正相色谱法纯化的纯化产物，其中R代表烷基 ，芳基烷基，羟基烷基，烷氧基烷基，酰氧基烷基，氨基烷基，烷基氨基烷基，烷氧基羰基氨基烷基，酰基氨基烷基或芳基。

公开(公告)号：US20050192311A1

公开(公告)日：2005-09-01

申请号：US11067718

申请日：2005-03-01

Applicant: Masashi Isozaki ,  Tetsuro Kawanishi

Inventor： Masashi Isozaki ,  Tetsuro Kawanishi

IPC: A61F2/82 ,  A61K31/436 ,  A61L31/00 ,  A61M29/02 ,  A61P31/10 ,  A61P35/00 ,  A61P37/06 ,  C07D498/18 ,  A61K31/4745 ,  C07D491/14

CPC classification number: C07D498/18

Abstract: Disclosed herein is a process for production of an O-alkylrapamycin derivative represented by the general formula (1) below by reaction between rapamycin and alkyl triflate in an organic solvent, characterized in that the reaction is carried out in the presence of trialkylamine. (where R denotes alkyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, acyloxyalkyl, aminoalkyl, alkylaminoalkyl, alkoxycarbonylaminoalkyl, acylaminoalkyl, or aryl.) This process is capable of producing O-alkylrapamycin derivative efficiently owing to improvement in reaction yields for O-alkylation.

Abstract translation: 本文公开了通过在有机溶剂中雷帕霉素和三氟甲磺酸烷基酯之间的反应制备由以下通式（1）表示的O-烷基雷帕霉素衍生物的方法，其特征在于反应在三烷基胺存在下进行。 （其中R表示烷基，芳基烷基，羟基烷基，烷氧基烷基，酰氧基烷基，氨基烷基，烷基氨基烷基，烷氧基羰基氨基烷基，酰氨基烷基或芳基）。由于O-烷基化的反应产率提高，该方法能够有效地生产O-烷基雷帕霉素衍生物。

公开(公告)号：US20070160646A1

公开(公告)日：2007-07-12

申请号：US11723367

申请日：2007-03-19

Applicant: Masashi Isozaki ,  Tetsuro Kawanishi

Inventor： Masashi Isozaki ,  Tetsuro Kawanishi

IPC: A61F2/02

CPC classification number: C07D498/18

Abstract: A stent coated by a compound represented by the general formula (1) below which is produced by reaction between rapamycin and alkyl triflate in an organic solvent which is a chlorine-containing organic solvent, wherein said reaction is carried out in the presence of trialkylamine, where R denotes alkyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, acyloxyalkyl, aminoalkyl, alkylaminoalkyl, alkoxycarbonylaminoalkyl, acylaminoalkyl, or aryl.

Abstract translation: 一种由下述通式（1）表示的化合物包被的支架，其通过雷帕霉素和三氟甲磺酸烷基酯在有机溶剂（其为含氯有机溶剂）中的反应制备，其中所述反应在三烷基胺存在下进行， 其中R表示烷基，芳基烷基，羟基烷基，烷氧基烷基，酰氧基烷基，氨基烷基，烷基氨基烷基，烷氧基羰基氨基烷基，酰氨基烷基或芳基。

公开(公告)号：US07193078B2

公开(公告)日：2007-03-20

申请号：US11067718

申请日：2005-03-01

Applicant: Masashi Isozaki ,  Tetsuro Kawanishi

Inventor： Masashi Isozaki ,  Tetsuro Kawanishi

IPC: C07D498/18

CPC classification number: C07D498/18

Abstract: Disclosed herein is a process for production of an O-alkylrapamycin derivative represented by the general formula (1) below by reaction between rapamycin and alkyl triflate in an organic solvent, characterized in that the reaction is carried out in the presence of trialkylamine. (where R denotes alkyl, arylalkyl, hydroxyalkyl, alkoxyalkyl, acyloxyalkyl, aminoalkyl, alkylaminoalkyl, alkoxycarbonylaminoalkyl, acylaminoalkyl, or aryl.) This process is capable of producing O-alkylrapamycin derivative efficiently owing to improvement in reaction yields for O-alkylation.

Abstract translation: 本文公开了通过在有机溶剂中雷帕霉素和三氟甲磺酸烷基酯之间的反应制备由以下通式（1）表示的O-烷基雷帕霉素衍生物的方法，其特征在于反应在三烷基胺存在下进行。 （其中R表示烷基，芳基烷基，羟基烷基，烷氧基烷基，酰氧基烷基，氨基烷基，烷基氨基烷基，烷氧基羰基氨基烷基，酰氨基烷基或芳基）。由于O-烷基化的反应产率提高，该方法能够有效地生产O-烷基雷帕霉素衍生物。

公开(公告)号：US5190961A

公开(公告)日：1993-03-02

申请号：US739437

申请日：1991-08-02

Applicant: Hirokazu Hasegawa ,  Isamu Endo ,  Shingo Koyama ,  Masashi Isozaki ,  Yukari Yoshiyama ,  Shigenori Nozawa ,  Norio Arakawa

Inventor： Hirokazu Hasegawa ,  Isamu Endo ,  Shingo Koyama ,  Masashi Isozaki ,  Yukari Yoshiyama ,  Shigenori Nozawa ,  Norio Arakawa

IPC: A61K31/17 ,  A61P1/04 ,  A61P31/04 ,  C07C335/08 ,  C07C335/14 ,  C07C335/16 ,  C07D213/75 ,  C07D295/08 ,  C07D295/096 ,  C07D307/52 ,  C07D333/20

CPC classification number: C07D213/75 ,  C07C335/08 ,  C07D295/096 ,  C07D307/52 ,  C07D333/20 ,  C07C2101/14

Abstract: Thiourea derivatives represented by the formula (I) ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and each represents a lower alkyl group, or R.sub.1 or R.sub.2 taken together represent a group having the formula --(CH.sub.2).sub.m --in which m is 4 or 5, R.sub.3 represents a lower alkyl group or a cycloalkyl group or a group having the formula--(CH.sub.2).sub.l --R.sub.4 in which R.sub.4 is a phenyl, naphthyl, pyridyl, furyl or thienyl group optionally having 1-3 substituents selected from the group consisting of lower alkyl, lower alkoxy, phenoxy, lower alkylthio, hydroxy, halogen, nitro, cyano and trifluoromethyl, and l represents an integer of 0 to 2 and n represents an integer of 1 to 5 or a physiologically acceptable salt thereof.The compounds of the invention are useful as a therapeutic agent for peptic ulcers which is also effective on prevention of the recurrence after discontinuation of the administration due to the antimicrobial activity against Helicobacter pyroli.

Abstract translation: 由式（I）表示的硫脲衍生物其中R 1和R 2相同或不同并且各自表示低级烷基，或者R 1或R 2一起表示具有式 - （CH 2）m - 其中m为4或5，R 3表示低级烷基或环烷基或具有式 - （CH 2）1 -R 4的基团，其中R 4为苯基，萘基，吡啶基，呋喃基或噻吩基， 3个选自低级烷基，低级烷氧基，苯氧基，低级烷硫基，羟基，卤素，硝基，氰基和三氟甲基的取代基，l表示0〜2的整数，n表示1〜5的整数或生理上 其可接受的盐。 本发明的化合物可用作消化性溃疡的治疗剂，其对于防止由于对幽门螺杆菌的抗微生物活性而在停止施用后的复发也是有效的。

公开(公告)号：US08945526B2

公开(公告)日：2015-02-03

申请号：US11812131

申请日：2007-06-15

Applicant: Hitoshi Akitsu ,  Eiichi Ozeki ,  Ryoji Fushimi ,  Shunsaku Kimura ,  Masashi Isozaki ,  Shigenori Nozawa

Inventor： Hitoshi Akitsu ,  Eiichi Ozeki ,  Ryoji Fushimi ,  Shunsaku Kimura ,  Masashi Isozaki ,  Shigenori Nozawa

IPC: A61K31/74 ,  C08G69/10 ,  A61K49/00 ,  B82Y5/00

CPC classification number: C08G69/10 ,  A61K49/0034 ,  A61K49/0043 ,  A61K49/0052 ,  A61K49/0093 ,  B82Y5/00

Abstract: The present invention provides a novel amphiphilic substance, a nanoparticle using the novel amphiphilic substance, which can be used as a nanocarrier having high biocompatibility, a drug delivery system and a probe useful for the system, and, a molecular imaging system and a probe useful for the system. An amphiphilic block polymer comprising a hydrophilic block; and a hydrophobic block, wherein the hydrophilic block is a hydrophilic polypeptide chain having 10 or more sarcosine units, and the hydrophobic block is a hydrophobic molecular chain comprising units selected from the group consisting of amino acid units and hydroxyl acid units as essential structural units, and having 5 or more of the essential structural units.

Abstract translation: 本发明提供一种新颖的两亲物质，使用该新型两亲性物质的纳米粒子，其可以用作具有高生物相容性的纳米载体，药物递送系统和可用于该系统的探针，以及分子成像系统和有用的探针 为系统。 包含亲水嵌段的两亲嵌段聚合物; 和疏水嵌段，其中所述亲水嵌段是具有10个或更多个肌氨酸单元的亲水性多肽链，疏水嵌段是包含选自氨基酸单元和羟基酸单元作为必需结构单元的单元的疏水分子链， 并具有5个以上的基本结构单元。

公开(公告)号：US20080279916A1

公开(公告)日：2008-11-13

申请号：US10594427

申请日：2005-03-25

Applicant: Masashi Isozaki ,  Keisuke Yoshino ,  Kyoko Taguchi ,  Masayo Kondo

Inventor： Masashi Isozaki ,  Keisuke Yoshino ,  Kyoko Taguchi ,  Masayo Kondo

IPC: A61K9/127 ,  A61P43/00

CPC classification number: A61K9/1271 ,  A61K9/1272 ,  A61K31/704

Abstract: A liposome preparation is provided. This liposome preparation is capable of stably encapsulating a drug which is unstable under an acidic condition, and such stable encapsulation is realized without detracting the effect realized by the modification of the membrane by a hydrophilic macromolecule such as stability in blood. More specifically, the liposome preparation comprises a unilamellar vesicle formed from a lipid bilayer comprising a phospholipid as its main membrane component, and an interior aqueous phase of the vesicle at a pH of up to 5. The liposome has a drug loaded therein, and the vesicle is modified with a hydrophilic macromolecule only on its exterior surface.

Abstract translation: 提供了脂质体制剂。 该脂质体制剂能够稳定地包封在酸性条件下不稳定的药物，并且实现这种稳定的包封，而不会降低通过亲水性高分子如血液稳定性改性膜所产生的效果。 更具体地说，脂质体制剂包括由包含磷脂作为其主要成分的脂质双层形成的单层囊泡和pH至多为5的囊泡的内部水相。脂质体中装载有药物，并且 囊泡仅在其外表面上用亲水性大分子修饰。

公开(公告)号：US5214053A

公开(公告)日：1993-05-25

申请号：US939692

申请日：1992-09-02

Applicant: Keiichi Nakazawa ,  Masashi Isozaki ,  Shingo Koyama

Inventor： Keiichi Nakazawa ,  Masashi Isozaki ,  Shingo Koyama

IPC: A61K31/335 ,  A61K31/357 ,  A61K31/435 ,  A61P1/04 ,  A61P31/00 ,  A61P31/04 ,  C07D317/48 ,  C07D317/58 ,  C07D317/66 ,  C07D319/18 ,  C07D405/12 ,  C07D405/14

CPC classification number: C07D405/12 ,  C07D317/66 ,  C07D319/18

Abstract: Thiourea derivatives represented by the formula (I) ##STR1## wherein R.sub.1 and R.sub.2 are the same or different and each represents a lower alkyl group, or R.sub.1 and R.sub.2 taken together represent a group having the formula --(CH.sub.2).sub.x --CHR.sub.3 --(CH.sub.2).sub.y -- in which R.sub.3 represents hydrogen or a lower alkyl group and x and y represent an integer of 0 to 2, respectively, A represents the formula --CH.dbd.CH-- or --CH.dbd.N--, 1 is 1 or 2, m represents an integer of 0 to 2 and n represents an integer of 1 to 5.The thiourea derivatives possess an antiulcer activity and an antimicrobial activity against Helicobacter pyroli and are useful as an antiulcer agent and an antimicrobial agent against Helicobacter pyroli.

公开(公告)号：US5037837A

公开(公告)日：1991-08-06

申请号：US607670

申请日：1990-11-01

Applicant: Yoshiyuki Shikata ,  Ryoichi Nanba ,  Isamu Endo ,  Masashi Isozaki ,  Tadashi Okumura ,  Masazumi Miyakoshi ,  Shingo Koyama

Inventor： Yoshiyuki Shikata ,  Ryoichi Nanba ,  Isamu Endo ,  Masashi Isozaki ,  Tadashi Okumura ,  Masazumi Miyakoshi ,  Shingo Koyama

IPC: A61K31/165 ,  A61K31/445 ,  A61P1/04 ,  A61P43/00 ,  C07D295/096

CPC classification number: C07D295/096

Abstract: Novel phenoxypropylamine derivative having the formula (I) ##STR1## wherein R.sub.1 and R.sub.2 represent a hydrogen atom, a hydroxy group, a lower alkyl group or a lower alkoxy group, and R.sub.3 and R.sub.4 represent a lower alkyl group, or R.sub.3 and R.sub.4 taken together represent a group having the formula (CH.sub.2).sub.m wherein m represents 4 or 5, and n represents an integer of from 2 to 6 or a pharmaceutically acceptable salt thereof.The compounds are useful as a 5-lipoxygenase inhibitor and an antiulcer agent.