公开(公告)号：US20110054168A1

公开(公告)日：2011-03-03

申请号：US12863297

申请日：2009-01-16

Applicant: Ayumu Kurimoto ,  Wataru Katoda ,  Kazuki Hashimoto ,  Kazuhiko Takashi

Inventor： Ayumu Kurimoto ,  Wataru Katoda ,  Kazuki Hashimoto ,  Kazuhiko Takashi

IPC: C07D473/18

CPC classification number: C07D473/18

Abstract: A method for preparing compound (4): wherein m and n are independently an integer of 2 to 5, R1 is C1-6 alkyl group, R2 and R3 are combined with an adjacent nitrogen atom to form pyrrolidine, morpholine, thiomorpholine, etc., and R4 is C1-3 alkyl group, or a pharmaceutically acceptable salt, which is useful as a medicament, which comprises step (a) for preparing compound (2): wherein m, n, R1, R2 and R3 are the same as defined above, or its salt which comprises subjecting compound (1): wherein k is an integer of 1 or 2, R is hydrogen atom, halogen atom, etc., or a salt thereof to debenzylation reaction, and then step (b) for preparing compound (4) or a pharmaceutically acceptable salt which comprises reacting compound (2) or its salt prepared in the above step (a) or salt thereof and compound (3): wherein R4 is C1-3 alkyl group, in the presence of a boron-containing reducing agent.

Abstract translation: 一种制备化合物（4）的方法：其中m和n独立地为2至5的整数，R 1为C 1-6烷基，R 2和R 3与相邻的氮原子结合形成吡咯烷，吗啉，硫代吗啉等。 ，和R4为C1-3烷基，或其药学上可接受的盐，其可用作药物，其包含用于制备化合物（2）的步骤（a）：其中m，n，R 1，R 2和R 3相同 或其盐，其包括使化合物（1）：其中k为1或2的整数，R为氢原子，卤素原子等或其盐进行脱苄基化反应，然后步骤（b）为 制备化合物（4）或其药学上可接受的盐，其包括使上述步骤（a）中制备的化合物（2）或其盐或其盐与化合物（3）反应：其中R 4为C 1-3烷基，在 含硼还原剂。

公开(公告)号：US20090192153A1

公开(公告)日：2009-07-30

申请号：US12067780

申请日：2006-09-21

Applicant: Kazuki Hashimoto ,  Tomoaki Nakamura ,  Kei Nakamura ,  Ayumu Kurimoto ,  Yoshiaki Isobe ,  Haruhisa Ogita ,  Ian Millichip ,  Thomas Mcinally ,  Roger Bonnert

Inventor： Kazuki Hashimoto ,  Tomoaki Nakamura ,  Kei Nakamura ,  Ayumu Kurimoto ,  Yoshiaki Isobe ,  Haruhisa Ogita ,  Ian Millichip ,  Thomas Mcinally ,  Roger Bonnert

IPC: A61K31/5377 ,  C07D473/34 ,  A61K31/522 ,  A61P37/08

CPC classification number: C07D473/18

Abstract: An adenine compound or its pharmaceutically acceptable salt as a medicament as shown following formula (1): wherein R1 is optionally substituted alkyl group, etc., X is oxygen atom, etc., A is 4 to 8 membered optionally substituted saturated or unsaturated heterocyclic group containing 1 to 2 hetero atoms selected from 1 to 3 nitrogen atoms, 0 to 1 oxygen atom and 0 to 1 sulfur atom, L1 and L2 are independently straight or branched chain alkylene, or a single bond, R2 is optionally substituted alkyl group, etc.

Abstract translation: 腺嘌呤化合物或其药学上可接受的盐作为如下式（1）所示的药物：其中R 1是任选取代的烷基等，X是氧原子等，A是4至8元任选取代的饱和或不饱和杂环 含有1至2个选自1至3个氮原子，0至1个氧原子和0至1个硫原子的杂原子的基团，L1和L2独立地为直链或支链亚烷基或单键，R2为任选取代的烷基， 等等

公开(公告)号：US20070225303A1

公开(公告)日：2007-09-27

申请号：US10594074

申请日：2005-03-25

Applicant: Haruhisa Ogita ,  Tomoaki Nakamura ,  Yoshiaki Isobe ,  Kazuki Hashimoto ,  Ayumu Kurimoto

Inventor： Haruhisa Ogita ,  Tomoaki Nakamura ,  Yoshiaki Isobe ,  Kazuki Hashimoto ,  Ayumu Kurimoto

IPC: A61K31/522 ,  C07D473/34

CPC classification number: C07D473/16 ,  A61K31/522 ,  A61K31/5377 ,  C07D473/18 ,  C07D473/24 ,  C07D473/34

Abstract: An 8-oxoadenine compound useful as an immuno-modulator having specific activity against Th1/Th2, specifically a prophylactic and therapeutic agent for a topical application for allergic diseases, viral diseases and cancers, which is represented by the following formula (1): wherein A is a group of a formula represented by the formula (2): wherein R2 is a substituted or unsubstituted alkyl group and so on, R3 is hydrogen atom or an alkyl group, R is a halogen atom and so on, n is 0˜2, X1 is oxygen atom, Z is straight or branched chain alkylene, and R1 is an alkyl group which is optionally substituted by hydroxy group, an alkoxy group, alkoxycarbonyl group and so on, or its pharmaceutically acceptable salt.

Abstract translation: 可用作对Th1 / Th2具有比活性的免疫调节剂的8-氧基腺嘌呤化合物，特别是用于过敏性疾病，病毒性疾病和癌症的局部应用的预防和治疗剂，其由下式（1）表示：其中 A是由式（2）表示的式的基团：其中R 2是取代或未取代的烷基等，R 3是氢原子或 烷基，R为卤素原子等，n为0〜2，X 1为氧原子，Z为直链或支链亚烷基，R 1为 任选被羟基，烷氧基，烷氧基羰基等取代的烷基或其药学上可接受的盐。

公开(公告)号：US08865896B2

公开(公告)日：2014-10-21

申请号：US12863291

申请日：2009-01-16

Applicant: Kazuki Hashimoto ,  Wataru Katoda ,  Kazuhiko Takahashi ,  Ayumu Kurimoto

Inventor： Kazuki Hashimoto ,  Wataru Katoda ,  Kazuhiko Takahashi ,  Ayumu Kurimoto

IPC: C07D473/02 ,  C07D413/14 ,  C07D473/18

CPC classification number: C07D473/18

Abstract: A method for producing adenine compound (1): wherein m and n are independently an integer of 2 to 5, R1 is C1-6 alkyl group, R2 and R3 are the same or different, and hydrogen atom, or C1-6 alkyl group, or R2 and R3 are combined with an adjacent nitrogen atom to form pyrrolidine, morpholine, piperidine, piperazine, etc., and R4 is C1-3 alkyl group, which comprises a step of reacting compound (2): and compound (3): in the presence of a boron-containing reducing agent.

Abstract translation: 一种腺嘌呤化合物（1）的制造方法，其中m和n分别为2〜5的整数，R1为C1-6烷基，R2和R3相同或不同，氢原子或C1-6烷基 ，或R2和R3与相邻的氮原子结合形成吡咯烷，吗啉，哌啶，哌嗪等，R4为C1-3烷基，其包括使化合物（2）与化合物（3）反应的步骤： ：在含硼还原剂的存在下。

公开(公告)号：US20110046369A1

公开(公告)日：2011-02-24

申请号：US12863291

申请日：2009-01-16

Applicant: Kazuki Hashimoto ,  Wataru Katoda ,  Kazuhiko Takahashi ,  Ayumu Kurimoto

Inventor： Kazuki Hashimoto ,  Wataru Katoda ,  Kazuhiko Takahashi ,  Ayumu Kurimoto

IPC: C07D473/18

CPC classification number: C07D473/18

Abstract: A method for producing adenine compound (1): wherein m and n are independently an integer of 2 to 5, R1 is C1-6 alkyl group, R2 and R3 are the same or different, and hydrogen atom, or C1-6 alkyl group, or R2 and R3 are combined with an adjacent nitrogen atom to form pyrrolidine, morpholine, piperidine, piperazine, etc., and R4 is C1-3 alkyl group, which comprises a step of reacting compound (2): and compound (3): in the presence of a boron-containing reducing agent.

Abstract translation: 一种腺嘌呤化合物（1）的制造方法，其中m和n分别为2〜5的整数，R1为C1-6烷基，R2和R3相同或不同，氢原子或C1-6烷基 ，或R2和R3与相邻的氮原子结合形成吡咯烷，吗啉，哌啶，哌嗪等，R4为C1-3烷基，其包括使化合物（2）与化合物（3）反应的步骤： ：在含硼还原剂的存在下。

公开(公告)号：US20110306610A1

公开(公告)日：2011-12-15

申请号：US13187260

申请日：2011-07-20

Applicant: Ayumu KURIMOTO ,  Kazuki Hashimoto ,  Yoshiaki Isobe ,  Stephen Brough ,  Ian Millichip ,  Hiroki Wada ,  Roger Bonnert ,  Thomas Mcinally

Inventor： Ayumu KURIMOTO ,  Kazuki Hashimoto ,  Yoshiaki Isobe ,  Stephen Brough ,  Ian Millichip ,  Hiroki Wada ,  Roger Bonnert ,  Thomas Mcinally

IPC: A61K31/522 ,  C07D413/14 ,  A61P37/08 ,  A61P37/00 ,  A61P31/12 ,  A61P35/00 ,  C07D473/18 ,  A61K31/5377

CPC classification number: C07D473/18 ,  A61K31/522 ,  A61K31/5377

Abstract: The present invention provides an 8-oxoadenine compound having immunemodulating activities such as an interferon inducing activity and useful as an antiviral agent and antiallergic agent, which is represented by the following formula (1): [wherein the ring A represents a 6-10 membered aromatic carbocyclic ring and the like, R represents a halogen atom, an alkyl group and the like, n represents an integer of 0-2, Z1 represents alkylene, X2 represents oxygen atom, sulfur atom, SO2, NR5, CO, CONR5, NR5CO and the like, Y1, Y2 and Y3 represent independently a single bond or an alkylene group, X1 represents oxygen atom, sulfur atom, NR4 (R4 is hydrogen atom or an alkyl group) or a single bond, R2 represents a substituted or unsubstituted alkyl group, R1 represents hydrogen atom, hydroxy group, an alkoxy group, an alkoxycarbonyl group or a haloalkyl group] or its pharmaceutically acceptable salt.

Abstract translation: 本发明提供具有免疫调节活性的8-氧代腺嘌呤化合物，例如干扰素诱导活性，可用作抗病毒剂和抗变应性剂，其由下式（1）表示：[其中环A表示6-10元 芳香族碳环等，R表示卤素原子，烷基等，n表示0-2的整数，Z1表示亚烷基，X2表示氧原子，硫原子，SO2，NR5，CO，CONR5，NR5CO 等等，Y1，Y2和Y3独立地表示单键或亚烷基，X1表示氧原子，硫原子，NR4（R4是氢原子或烷基）或单键，R2表示取代或未取代的烷基 基团，R 1表示氢原子，羟基，烷氧基，烷氧基羰基或卤代烷基]或其​​药学上可接受的盐。

公开(公告)号：US20090105212A1

公开(公告)日：2009-04-23

申请号：US12067651

申请日：2006-09-22

Applicant: Yoshiaki Isobe ,  Ayumu Kurimoto ,  Kazuki Hashimoto ,  Tomoaki Nakamura ,  Kei Nakamura

Inventor： Yoshiaki Isobe ,  Ayumu Kurimoto ,  Kazuki Hashimoto ,  Tomoaki Nakamura ,  Kei Nakamura

IPC: A61K31/522 ,  C07D473/34 ,  A61P31/18

CPC classification number: C07D473/18

Abstract: A novel adenine compound represented by the formula (1): wherein A represents an (un)substituted aromatic carbocycle or (un)substituted aromatic heterocycle; L1, L2, and L3 each independently represents linear or branched alkylene, etc.; R1 represents (un)substituted alkyl, (un)substituted aryl, etc.; R2 represents hydrogen or (un) substituted alkyl; R3 represents (un)substituted alkyl, etc., provided that R3 may be bonded to L2 or L3 to form a nitrogenous saturated heterocycle; and X represents oxygen, etc.; or a pharmaceutically acceptable salt of the compound. The compound and salt are useful as a medicine.

Abstract translation: 由式（1）表示的新型腺嘌呤化合物：其中A表示（un）取代的芳族碳环或（un）取代的芳族杂环; L1，L2和L3各自独立地表示直链或支链亚烷基等; R1表示（un）取代的烷基，（un）取代的芳基等; R2代表氢或（未）取代的烷基; R3表示（un）取代的烷基等，条件是R3可以键合到L2或L3以形成含氮饱和杂环; X表示氧等。 或该化合物的药学上可接受的盐。 化合物和盐可用作药物。

公开(公告)号：US20140045837A1

公开(公告)日：2014-02-13

申请号：US14058064

申请日：2013-10-21

Applicant: Ayumu Kurimoto ,  Kazuki Hashimoto ,  Yoshiaki Isobe ,  Stephen Brough ,  Ian Millichip ,  Hiroki Wada ,  Roger Bonnert ,  Thomas Mcinally

Inventor： Ayumu Kurimoto ,  Kazuki Hashimoto ,  Yoshiaki Isobe ,  Stephen Brough ,  Ian Millichip ,  Hiroki Wada ,  Roger Bonnert ,  Thomas Mcinally

IPC: C07D473/18

CPC classification number: C07D473/18 ,  A61K31/522 ,  A61K31/5377

Abstract: The present invention provides an 8-oxoadenine compound having immunomodulating activities such as an interferon inducing activity and useful as an antiviral agent and antiallergic agent, which is represented by the following formula (1): [wherein the ring A represents a 6-10 membered aromatic carbocyclic ring and the like, R represents a halogen atom, an alkyl group and the like, n represents an integer of 0-2, Z1 represents alkylene, X2 represents oxygen atom, sulfur atom, SO2, NR5, CO, CONR5, NR5CO and the like, Y1, Y2 and Y3 represent independently a single bond or an alkylene group, X1 represents oxygen atom, sulfur atom, NR4 (R4 is hydrogen atom or an alkyl group) or a single bond, R2 represents a substituted or unsubstituted alkyl group, R1 represents hydrogen atom, hydroxy group, an alkoxy group, an alkoxycarbonyl group or a haloalkyl group] or its pharmaceutically acceptable salt.

Abstract translation: 本发明提供具有免疫调节活性的8-氧代腺嘌呤化合物，例如干扰素诱导活性，可用作抗病毒剂和抗变应性剂，其由下式（1）表示：[其中环A表示6-10元 芳香族碳环等，R表示卤素原子，烷基等，n表示0-2的整数，Z1表示亚烷基，X2表示氧原子，硫原子，SO2，NR5，CO，CONR5，NR5CO 等等，Y1，Y2和Y3独立地表示单键或亚烷基，X1表示氧原子，硫原子，NR4（R4是氢原子或烷基）或单键，R2表示取代或未取代的烷基 基团，R 1表示氢原子，羟基，烷氧基，烷氧基羰基或卤代烷基]或其​​药学上可接受的盐。

公开(公告)号：US08575180B2

公开(公告)日：2013-11-05

申请号：US13187260

申请日：2011-07-20

Applicant: Ayumu Kurimoto ,  Kazuki Hashimoto ,  Yoshiaki Isobe ,  Stephen Brough ,  Ian Millichip ,  Hiroki Wada ,  Roger Bonnert ,  Thomas Mcinally

Inventor： Ayumu Kurimoto ,  Kazuki Hashimoto ,  Yoshiaki Isobe ,  Stephen Brough ,  Ian Millichip ,  Hiroki Wada ,  Roger Bonnert ,  Thomas Mcinally

IPC: A61K31/52 ,  C07D473/00

CPC classification number: C07D473/18 ,  A61K31/522 ,  A61K31/5377

Abstract: The present invention provides an 8-oxoadenine compound having immunemodulating activities such as an interferon inducing activity and useful as an antiviral agent and antiallergic agent, which is represented by the following formula (1): [wherein the ring A represents a 6-10 membered aromatic carbocyclic ring and the like, R represents a halogen atom, an alkyl group and the like, n represents an integer of 0-2, Z1 represents alkylene, X2 represents oxygen atom, sulfur atom, SO2, NR5, CO, CONR5, NR5CO and the like, Y1, Y2 and Y3 represent independently a single bond or an alkylene group, X1 represents oxygen atom, sulfur atom, NR4 (R4 is hydrogen atom or an alkyl group) or a single bond, R2 represents a substituted or unsubstituted alkyl group, R1 represents hydrogen atom, hydroxy group, an alkoxy group, an alkoxycarbonyl group or a haloalkyl group] or its pharmaceutically acceptable salt.

Abstract translation: 本发明提供具有免疫调节活性的8-氧代腺嘌呤化合物，例如干扰素诱导活性，可用作抗病毒剂和抗变应性剂，其由下式（1）表示：[其中环A表示6-10元 芳香族碳环等，R表示卤素原子，烷基等，n表示0-2的整数，Z1表示亚烷基，X2表示氧原子，硫原子，SO2，NR5，CO，CONR5，NR5CO 等等，Y1，Y2和Y3独立地表示单键或亚烷基，X1表示氧原子，硫原子，NR4（R4是氢原子或烷基）或单键，R2表示取代或未取代的烷基 基团，R 1表示氢原子，羟基，烷氧基，烷氧基羰基或卤代烷基]或其​​药学上可接受的盐。

公开(公告)号：US20090118263A1

公开(公告)日：2009-05-07

申请号：US12067649

申请日：2006-09-20

Applicant: Kazuki Hashimoto ,  Tomoaki Nakamura ,  Kei Nakamura ,  Ayumu Kurimoto ,  Yoshiaki Isobe

Inventor： Kazuki Hashimoto ,  Tomoaki Nakamura ,  Kei Nakamura ,  Ayumu Kurimoto ,  Yoshiaki Isobe

IPC: A61K31/551 ,  C07D473/00 ,  A61K31/522 ,  C07D413/02 ,  A61K31/5386 ,  A61P37/08 ,  A61P35/00 ,  A61P37/02 ,  A61K31/5377 ,  A61K31/496 ,  C07D243/08

CPC classification number: C07D473/16 ,  C07D473/18 ,  C07D519/00

Abstract: An adenine compound represented by the formula (1): (1) [wherein A1 and A2 each independently represents an (un)substituted aromatic carbocycle or (un)substituted aromatic heterocycle; L1, L2, and L3 each independently represents alkylene or a single bond, provided that any methylene or methine group in L2 or L3 may be bonded to the nitrogen atom adjacent to L2 and L3 to form a 4- to 7-membered saturated nitrogenous heterocycle; L4 represents alkylene or a single bond; R1 represents (un)substituted alkyl, (un)substituted aryl, etc.; R2 represents hydrogen or (un)substituted alkyl; R3 represents (un)substituted alkyl, etc.; and X represents oxygen, etc.] or a pharmaceutically acceptable salt of the compound. The compound and salt are useful as a medicine.

Abstract translation: 由式（1）表示的腺嘌呤化合物：（1）[其中，A1和A2各自独立地表示（un）取代的芳族碳环或（un）取代的芳族杂环; L1，L2和L3各自独立地表示亚烷基或单键，条件是L2或L3中的任何亚甲基或次甲基可以键合到与L2和L3相邻的氮原子上以形成4-至7-元饱和含氮杂环 ; L4表示亚烷基或单键; R1表示（un）取代的烷基，（un）取代的芳基等; R2代表氢或（未）取代的烷基; R3表示（un）取代的烷基等; X表示氧等]或化合物的药学上可接受的盐。 化合物和盐可用作药物。