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1. 发明授权

US5674732A Rapamycin producer 失效
标题翻译：雷帕霉素生产者
公开(公告)号：US5674732A
公开(公告)日：1997-10-07
申请号：US325378
申请日：1994-10-26
申请人： Hiroyuki Nishida , Tatsuo Sakakibara , Yuji Yamauchi , Taisuke Inagaki , Yasuhiro Kojima , Nakao Kojima
发明人： Hiroyuki Nishida , Tatsuo Sakakibara , Yuji Yamauchi , Taisuke Inagaki , Yasuhiro Kojima , Nakao Kojima
IPC分类号： C12N1/20
CPC分类号： C12R1/045
摘要： The present invention provides a novel culture which belongs to Actinoplanes (Actinoplanes sp. FERM BP-3832). This culture is capable of producing rapamycin more than ten times efficiently than the cultures which have been reported (e.g., Streptomyces hygroscopicus ATCC 29253). The present invention provides a process for the production of rapamycin which comprises cultivating Actinoplanes sp. FERM BP-3832 and thereafter isolating rapamycin from the fermentation mixture.
摘要翻译： PCT No.PCT / US93 / 01534 Sec。 371日期：1994年10月26日 102（e）日期1994年10月26日PCT 1993年2月26日PCT PCT。公开号WO93 / 22446 日期：11月11日，11日本发明提供了属于动植物平面（Actinoplanes sp.FERM BP-3832）的新型培养物。该培养物能够比已报道的培养物（例如，吸水链霉菌ATCC 29253）有效地产生雷帕霉素的十倍以上。本发明提供了一种雷帕霉素的生产方法，其包括培养飞蓟素sp。 FERM BP-3832，然后从发酵混合物中分离雷帕霉素。

2. 发明授权

US06187568B1 Macrocyclic lactone compounds and their production process 失效
标题翻译：大环内酯化合物及其生产工艺
公开(公告)号：US06187568B1
公开(公告)日：2001-02-13
申请号：US09378062
申请日：1999-08-20
申请人： Hiroyuki Nishida , Yuji Yamauchi , Taisuke Inagaki , Yasuhiro Kojima , Nakao Kojima
发明人： Hiroyuki Nishida , Yuji Yamauchi , Taisuke Inagaki , Yasuhiro Kojima , Nakao Kojima
IPC分类号： C12P1718
CPC分类号： C07D498/18 , C12P17/188
摘要： This invention provides a process for producing a macrocyclic lactone compound, which comprises cultivating Actinoplanes sp. FERM BP-3832, in the presence of L-proline, L-hydroxyproline or L-nipecotic acid, and then isolating a macrocylic lactone compound from the fermentation broth. The compounds produced by this process include a compound of the following formula: The present invention also relates to a pharmaceutical composition comprising the same, which is useful as immunosuppressive, antimycotic, antitumor agent or the like.
摘要翻译：本发明提供了一种制备大环内酯化合物的方法，其包括培养活性平板体。 FERM BP-3832，在L-脯氨酸，L-羟脯氨酸或L-乳酸的存在下，然后从发酵液中分离大环内酯化合物。通过该方法制备的化合物包括下式的化合物：本发明还涉及包含该化合物的药物组合物，其可用作免疫抑制，抗真菌剂，抗肿瘤剂等。

3. 发明授权

US6001998A Macrocyclic lactone compounds and their production process 失效
标题翻译：大环内酯化合物及其生产工艺
公开(公告)号：US6001998A
公开(公告)日：1999-12-14
申请号：US836213
申请日：1997-10-27
申请人： Hiroyuki Nishida , Yuji Yamauchi , Taisuke Inagaki , Yasuhiro Kojima , Nakao Kojima
发明人： Hiroyuki Nishida , Yuji Yamauchi , Taisuke Inagaki , Yasuhiro Kojima , Nakao Kojima
IPC分类号： B65B57/02 , A61K31/40 , A61K31/401 , A61K31/445 , A61K31/70 , A61K35/00 , A61P31/04 , A61P35/00 , A61P37/06 , B65G43/00 , C07D20060101 , C07D209/00 , C07D273/00 , C07D311/00 , C07D498/18 , C07H19/01 , C12P1/06 , C12P17/18 , C12R1/045 , G01B11/26 , G05B19/02 , G05B19/05 , G05D3/00 , G05D3/12
CPC分类号： C07D498/18 , C12P17/188
摘要： This invention provides a process for producing a macrocyclic lactone compound, which comprises cultivating Actinoplanes sp. FERM BP-3832, in the presence of L-proline, L-hydroxyproline or L-nipecotic acid, and then isolating a macrocyclic lactone compound from the fermentation broth. The compounds produced by this process include a compound of formula (I). The present invention also relates to a pharmaceutical composition comprising the same, which is useful as immunosuppressive, antimycotic, antitumor agent or the like.
摘要翻译： PCT No.PCT / IB95 / 00870 Sec。 371日期1997年10月27日第 102（e）1997年10月27日PCT PCT 1995年10月13日PCT公布。公开号WO96 / 15131 日期1996年5月23日本发明提供了一种制备大环内酯化合物的方法，其包括培养活性平板体。 FERM BP-3832，在L-脯氨酸，L-羟脯氨酸或L-乳酸的存在下，然后从发酵液中分离大环内酯化合物。通过该方法制备的化合物包括式（I）的化合物。本发明还涉及含有该组合物的药物组合物，其可用作免疫抑制，抗真菌剂，抗肿瘤剂等。

4. 发明授权

US06194442B1 5-substituted picolinic acid compounds and their method of use 失效
标题翻译： 5-取代吡啶甲酸化合物及其使用方法
公开(公告)号：US06194442B1
公开(公告)日：2001-02-27
申请号：US09460483
申请日：1999-12-14
申请人： Hideo Hirai , Katsuomi Ichikawa , Nakao Kojima , Hiroyuki Nishida , Kunio Satake , Nobuji Yoshikawa
发明人： Hideo Hirai , Katsuomi Ichikawa , Nakao Kojima , Hiroyuki Nishida , Kunio Satake , Nobuji Yoshikawa
IPC分类号： A61K3144
CPC分类号： A61K31/44 , Y02A50/411
摘要： The present invention provides novel 5-substituted picolinic acid compounds of formula (I) or a pharmaceutically acceptable salt thereof: wherein R1 and R2 are independently H, C2-C6 acyl or halo-substituted benzoyl; and R3 is —C(O)O—C1-C6 alkyl, C(O)OH, CN, CONH2, CONHCH3, CON(CH3)2, 1-methyltetrazole or 2-methyltetrazole, with the proviso that when R2 is acetyl and R3 is methoxycarbonyl, R1 is not H; and that when R3 is CN, CONH2, CONHCH3, CON(CH3)2, 1-methyltetrazole or 2-methyltetrazole, R1 and R2 are H. The present invention also relates to a pharmaceutical composition comprising compound of the present invention, which is useful in the treatment of IL-1 and TNF mediated diseases or the like. The present invention further relates to a process for producing the compounds of the formula (I).
摘要翻译：本发明提供式（I）的新的5-取代的吡啶甲酸化合物或其药学上可接受的盐：其中R 1和R 2独立地为H，C 2 -C 6酰基或卤素取代的苯甲酰基; 并且R 3是-C（O）O-C 1 -C 6烷基，C（O）OH，CN，CONH 2，CONHCH 3，CON（CH 3）2,1-甲基四唑或2-甲基四唑，条件是当R 2是乙酰基和 R3是甲氧基羰基，R1不是H; 当R3为CN，CONH2，CONHCH3，CON（CH3）2,1-甲基四唑或2-甲基四唑时，R 1和R 2为H.本发明还涉及含有本发明化合物的药物组合物，其有用在治疗IL-1和TNF介导的疾病等中。本发明还涉及制备式（I）化合物的方法。

5. 发明授权

US06416979B1 5-substituted picolinic acid compounds production by Marasmiellus sp 失效
标题翻译：由马拉斯马司属（Malasmiellus sp。）生产的5-取代吡啶甲酸化合物
公开(公告)号：US06416979B1
公开(公告)日：2002-07-09
申请号：US09657730
申请日：2000-09-08
申请人： Hideo Hirai , Katsuomi Ichikawa , Nakao Kojima , Hiroyuki Nishida , Kunio Satake , Nobuji Yoshikawa
发明人： Hideo Hirai , Katsuomi Ichikawa , Nakao Kojima , Hiroyuki Nishida , Kunio Satake , Nobuji Yoshikawa
IPC分类号： C12P1712
CPC分类号： A61K31/44
摘要： The present invention provides novel 5-substituted picolinic acid compounds of formula (I) or a pharmaceutically acceptable salt thereof: wherein R1 and R2 are independently H, C2-C6 acyl or halo-substituted benzoyl; and R3 is —C(O)O—C1-C6 alkyl, C(O)OH, CN, CONH2, CONHCH3, CON(CH3)2, 1-methyltetrazole or 2-methyltetrazole, with the proviso that when R2 is acetyl and R3 is methoxycarbonyl, R1 is not H; and that when R3 is CN, CONH2, CONHCH3, CON(CH3)2, 1-methyltetrazole or 2-methyltetrazole, R1 and R2 are H. The present invention also relates to a pharmaceutical composition comprising compound of the present invention, which is useful in the treatment of IL-1 and TNF mediated diseases or the like. The present invention further relates to a process for producing the compounds of the formula (I).
摘要翻译：本发明提供式（I）的新的5-取代的吡啶甲酸化合物或其药学上可接受的盐：其中R 1和R 2独立地为H，C 2 -C 6酰基或卤素取代的苯甲酰基; 并且R 3是-C（O）O-C 1 -C 6烷基，C（O）OH，CN，CONH 2，CONHCH 3，CON（CH 3）2,1-甲基四唑或2-甲基四唑，条件是当R 2是乙酰基和 R3是甲氧基羰基，R1不是H; 当R3为CN，CONH2，CONHCH3，CON（CH3）2,1-甲基四唑或2-甲基四唑时，R 1和R 2为H.本发明还涉及含有本发明化合物的药物组合物，其有用在治疗IL-1和TNF介导的疾病等中。本发明还涉及制备式（I）化合物的方法。

6. 发明授权

US06221899B1 Terpenoid lactone compounds and their production process 失效
标题翻译：萜类内酯化合物及其制备方法
公开(公告)号：US06221899B1
公开(公告)日：2001-04-24
申请号：US09596728
申请日：2000-06-16
申请人： Hiroyuki Nishida , Masaya Ikunaka , Nobuji Yoshikawa , Katsuomi Ichikawa , Nakao Kojima
发明人： Hiroyuki Nishida , Masaya Ikunaka , Nobuji Yoshikawa , Katsuomi Ichikawa , Nakao Kojima
IPC分类号： A61K3135
CPC分类号： A61K31/4741 , A61K31/365 , A61K31/366 , Y02A50/411
摘要： This invention provides terpenoid lactone compounds, and processes for producing the terpenoid lactone compounds, which comprise cultivating Oidiodedron griseum FERM BP-5778 and then isolating the terpenoid lactone compounds from the fermentation broth. The present invention also provides a pharmaceutical composition comprising the teipenoid lactone compound, which is useful in the treatment of IL-1 and TNF mediated diseases or the like.
摘要翻译：本发明提供萜类内酯化合物，以及萜类内酯化合物的制备方法，其包括培育Oidiodedron griseum FERM BP-5778，然后从发酵液中分离萜类内酯化合物。本发明还提供了一种药物组合物，其包含可用于治疗IL-1和TNF介导的疾病等的脯氨酸内酯化合物。

7. 发明授权

US6034107A 5-Substituted picolinic acid compounds and their production process 失效
标题翻译： 5-取代的吡啶甲酸化合物及其制备方法
公开(公告)号：US6034107A
公开(公告)日：2000-03-07
申请号：US178949
申请日：1998-10-26
申请人： Hideo Hirai , Katsuomi Ichikawa , Nakao Kojima , Hiroyuki Nishida , Kunio Satake , Nobuji Yoshikawa
发明人： Hideo Hirai , Katsuomi Ichikawa , Nakao Kojima , Hiroyuki Nishida , Kunio Satake , Nobuji Yoshikawa
IPC分类号： C07D213/78 , A61K31/00 , A61K31/44 , A61K31/4427 , A61K31/4439 , A61P11/00 , A61P19/00 , A61P19/02 , A61P29/00 , A61P43/00 , C07D213/79 , C07D213/81 , C07D213/84 , C07D401/04 , C12N1/14 , C12P17/12 , C12P17/16 , C12R1/645
CPC分类号： C07D213/79 , C07D213/81 , C07D213/84 , C07D401/04 , C12P17/12
摘要： The present invention provides novel 5-substituted picolinic acid compounds of formula (I) or a pharmaceutically acceptable salt thereof: ##STR1## wherein R.sup.1 and R.sup.2 are independently H, C.sub.2 -C.sub.6 acyl or halo-substituted benzoyl; and R.sup.3 is --C(O)O--C.sub.1 -C.sub.6 alkyl, C(O)OH, CN, CONH.sub.2, CONHCH.sub.3, CON(CH.sub.3).sub.2, 1-methyltetrazole or 2-methyltetrazole, with the proviso that when R.sub.2 is acetyl and R.sup.3 is methoxycarbonyl, R.sup.1 is not H; and that when R.sup.3 is CN, CONH.sub.2, CONHCH.sub.3, CON(CH.sub.3).sub.2, 1-methyltetrazole or 2-methyltetrazole, R.sup.1 and R.sup.2 are H.The present invention also relates to a pharmaceutical composition comprising compound of the present invention, which is useful in the treatment of IL-1 and TNF mediated diseases or the like.The present invention further relates to a process for producing the compounds of the formula (I).
摘要翻译：本发明提供式（I）的新的5-取代的吡啶甲酸化合物或其药学上可接受的盐：其中R 1和R 2独立地为H，C 2 -C 6酰基或卤素取代的苯甲酰基; 并且R 3是-C（O）O-C 1 -C 6烷基，C（O）OH，CN，CONH 2，CONHCH 3，CON（CH 3）2,1-甲基四唑或2-甲基四唑，条件是当R 2是乙酰基和 R3是甲氧基羰基，R1不是H; 当R 3为CN时，CONH 2，CONHCH 3，CON（CH 3）2，1-甲基四唑或2-甲基四唑，R 1和R 2为H.本发明还涉及含有本发明化合物的药物组合物，在治疗IL-1和TNF介导的疾病等中。本发明还涉及制备式（I）化合物的方法。

8. 发明授权

US06391616B1 Oidiodendron strain for the production of terpenoid lactone compounds 失效
标题翻译：用于生产萜类内酯化合物的Oidiodendron菌株
公开(公告)号：US06391616B1
公开(公告)日：2002-05-21
申请号：US09596140
申请日：2000-06-16
申请人： Hiroyuki Nishida , Masaya Ikunaka , Nobuji Yoshikawa , Katsuomi Ichikawa , Nakao Kojima
发明人： Hiroyuki Nishida , Masaya Ikunaka , Nobuji Yoshikawa , Katsuomi Ichikawa , Nakao Kojima
IPC分类号： C12N114
CPC分类号： C07D307/92 , A61K31/365 , A61K31/366 , A61K31/4741 , C07D311/92 , C07D491/06 , C07D493/06 , Y02A50/411
摘要： This invention provides terpenoid lactone compounds, and processes for producing the terpenoid lactone compounds, which comprise cultivating Oidiodedron griseum FERM BP-5778 and then isolating the terpenoid lactone compounds from the fermentation broth. The present invention also provides a pharmaceutical composition comprising the terpenoid lactone compound, which is useful in the treatment of IL-1 and TNF mediated diseases or the like.
摘要翻译：本发明提供萜类内酯化合物，以及萜类内酯化合物的制备方法，其包括培育Oidiodedron griseum FERM BP-5778，然后从发酵液中分离萜类内酯化合物。本发明还提供了包含萜类内酯化合物的药物组合物，其可用于治疗IL-1和TNF介导的疾病等。

9. 发明授权

US06225339B1 Terpenoid lactone compounds and their production process 失效
标题翻译：萜类内酯化合物及其制备方法
公开(公告)号：US06225339B1
公开(公告)日：2001-05-01
申请号：US09232080
申请日：1999-01-15
申请人： Hiroyuki Nishida , Masaya Ikunaka , Nobuji Yoshikawa , Katsuomi Ichikawa , Nakao Kojima
发明人： Hiroyuki Nishida , Masaya Ikunaka , Nobuji Yoshikawa , Katsuomi Ichikawa , Nakao Kojima
IPC分类号： A61K3135
CPC分类号： C07D307/92 , A61K31/365 , A61K31/366 , A61K31/4741 , C07D311/92 , C07D491/06 , C07D493/06 , Y02A50/411
摘要： This invention provides terpenoid lactone compounds, and processes for producing the terpenoid lactone compounds, which comprise cultivating Oidiodedron griseum FERM BP-5778 and then isolating the terpenoid lactone compounds from the fermentation broth. The present invention also provides a pharmaceutical composition comprising the terpenoid lactone compound, which is useful in the treatment of IL-1 and TNF mediated diseases or the like.
摘要翻译：本发明提供萜类内酯化合物，以及萜类内酯化合物的制备方法，其包括培育Oidiodedron griseum FERM BP-5778，然后从发酵液中分离萜类内酯化合物。本发明还提供了包含萜类内酯化合物的药物组合物，其可用于治疗IL-1和TNF介导的疾病等。

10. 发明授权

US5885959A Cyclic peptide compounds and their production process 失效
标题翻译：环肽化合物及其制备方法
公开(公告)号：US5885959A
公开(公告)日：1999-03-23
申请号：US999627
申请日：1997-12-03
申请人： Hideo Hirai , Nakao Kojima , Hiroyuki Nishida , Toshiyuki Saito , Nobuji Yoshikawa
发明人： Hideo Hirai , Nakao Kojima , Hiroyuki Nishida , Toshiyuki Saito , Nobuji Yoshikawa
IPC分类号： C12P21/04 , A61K38/00 , A61P25/04 , A61P25/30 , A61P39/02 , C07K5/12 , C12P21/02 , C12R1/645 , A61K38/12 , C07K5/00 , C07K7/00 , C07K16/00
CPC分类号： C07K5/126 , C12P21/02 , A61K38/00
摘要： This invention provides processes for producing novel cyclic peptide compounds, which comprise cultivating Ctenomyces serratus FERM BP-5731 and then isolating the cyclic peptide compounds from the fermentation broth. The compounds produced by these processes include a cyclic peptide compound of the following formula (I): ##STR1## The present invention also relates to a pharmaceutical composition comprising the same, which is useful in the treatment of severe pain, detoxication of narcotics dependency or acute narcotics intoxication or the like.
摘要翻译：本发明提供了生产新型环肽化合物的方法，其包括培养C ivating atus ERM FERM BP-5731，然后从发酵液中分离出环状肽化合物。通过这些方法制备的化合物包括下式（I）的环肽化合物：（I）本发明还涉及包含其的药物组合物，其可用于治疗严重疼痛，解毒麻醉品依赖或急性毒品中毒等。

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