公开(公告)号：EP2428508A1

公开(公告)日：2012-03-14

申请号：EP10772177.1

申请日：2010-05-06

申请人： Astellas Pharma Inc. ,  Kotobuki Pharmaceutical Co., Ltd.

发明人： SHIMADA, Itsuro ,  KUROSAWA, Kazuo ,  MATSUYA, Takahiro ,  IIKUBO, Kazuhiko ,  KONDOH, Yutaka ,  KAMIKAWA, Akio ,  TOMIYAMA, Hiroshi ,  IWAI, Yoshinori

IPC分类号： C07D239/48 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/505 ,  A61K31/506 ,  A61K31/5377 ,  A61K31/541 ,  A61K31/55 ,  A61P35/00 ,  A61P43/00 ,  C07D241/26 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/08 ,  C07D491/113

CPC分类号： C07D239/48 ,  C07D241/26 ,  C07D241/28 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/08 ,  C07D491/113

摘要： Provided is a compound useful as an inhibitor against the kinase activity of EML4-ALK fusion protein.
As a result of intensive and extensive studies on compounds having inhibitory activity against the kinase activity of EMLA-ALK fusion protein, the present inventors found that the diamino heterocyclic carboxamide compounds of the present invention had inhibitory activity against the kinase activity of EML4-ALK fusion protein. By this finding, the present invention was completed. The compounds of the present invention can be used as a pharmaceutical composition for preventing and/or treating cancer, such as lung cancer, non-small cell lung cancer, and small cell lung cancer.

摘要翻译： 提供了可用作抑制EML4-ALK融合蛋白的激酶活性的化合物。 作为对具有针对EMLA-ALK融合蛋白的激酶活性的抑制活性的化合物进行了深入研究的结果，本发明人发现本发明的二氨基杂环羧酰胺化合物对EML4-ALK融合体的激酶活性具有抑制活性 蛋白。 通过这一发现，完成了本发明。 本发明的化合物可以用作预防和/或治疗癌症的药物组合物，例如肺癌，非小细胞肺癌和小细胞肺癌。

公开(公告)号：EP2428508B1

公开(公告)日：2015-12-16

申请号：EP10772177.1

申请日：2010-05-06

申请人： Astellas Pharma Inc. ,  Kotobuki Pharmaceutical Co., Ltd.

发明人： SHIMADA, Itsuro ,  KUROSAWA, Kazuo ,  MATSUYA, Takahiro ,  IIKUBO, Kazuhiko ,  KONDOH, Yutaka ,  KAMIKAWA, Akio ,  TOMIYAMA, Hiroshi ,  IWAI, Yoshinori

IPC分类号： C07D239/48 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/505 ,  A61K31/506 ,  A61P35/00 ,  C07D241/26 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/08 ,  C07D491/113

CPC分类号： C07D239/48 ,  C07D241/26 ,  C07D241/28 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/08 ,  C07D491/113

公开(公告)号：EP4253373A1

公开(公告)日：2023-10-04

申请号：EP21898136.3

申请日：2021-11-29

申请人： Astellas Pharma Inc. ,  Kotobuki Pharmaceutical Co., Ltd.

发明人： WATANABE, Hideyuki ,  KAMIKUBO, Takashi ,  KAMIKAWA, Akio ,  WASHIO, Takuya ,  SEKI, Yohei ,  OKUYAMA, Keiichiro ,  IKEDA, Osamu ,  TOMIYAMA, Hiroshi ,  IWAI, Yoshinori ,  NAKAMURA, Akihiko ,  MIYASAKA, Kozo

IPC分类号： C07D401/12 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/496 ,  A61K31/501 ,  A61K31/519 ,  A61P35/00 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D407/14 ,  C07D413/04 ,  C07D413/14 ,  C07D487/04

摘要： A compound useful as an active ingredient of a pharmaceutical composition for treatment of cancer related to activation of immune cells or cancer resistant to anti-PD-1 antibody/anti-PD-L1 antibody therapy is provided.
The present inventors have conducted studies on a compound useful as an active ingredient of a pharmaceutical composition for treatment of cancer related to activation of immune cells or cancer resistant to anti-PD-1 antibody/anti-PD-L1 antibody therapy, and confirmed that a heteroaryl carboxamide compound has DGK ξ (DGKzeta) inhibitory effect, leading to completion of the present invention. The heteroaryl carboxamide compound of the present invention has DGK ξ inhibitory effect, and can be used as a therapeutic agent for treatment of cancer related to activation of immune cells or cancer resistant to anti-PD-1 antibody/anti-PD-L1 antibody therapy.

公开(公告)号：EP2428508B9

公开(公告)日：2016-04-20

申请号：EP10772177.1

申请日：2010-05-06

申请人： Astellas Pharma Inc. ,  Kotobuki Pharmaceutical Co., Ltd.

发明人： SHIMADA, Itsuro ,  KUROSAWA, Kazuo ,  MATSUYA, Takahiro ,  IIKUBO, Kazuhiko ,  KONDOH, Yutaka ,  KAMIKAWA, Akio ,  TOMIYAMA, Hiroshi ,  IWAI, Yoshinori

IPC分类号： C07D239/48 ,  A61K31/4965 ,  A61K31/497 ,  A61K31/505 ,  A61K31/506 ,  A61P35/00 ,  C07D241/26 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/08 ,  C07D491/113

CPC分类号： C07D239/48 ,  C07D241/26 ,  C07D241/28 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D405/12 ,  C07D405/14 ,  C07D409/12 ,  C07D413/12 ,  C07D417/12 ,  C07D471/08 ,  C07D491/113

公开(公告)号：EP2172461A1

公开(公告)日：2010-04-07

申请号：EP08777903.9

申请日：2008-07-04

申请人： Astellas Pharma Inc.

发明人： KONDOH, Yutaka ,  IIKUBO, Kazuhiko ,  KUROMITSU, Sadao ,  SHINDO, Nobuaki ,  SOGA, Takatoshi ,  FURUTANI, Takashi ,  SHIMADA, Itsuro ,  MATSUYA, Takahiro ,  KUROSAWA, Kazuo ,  KAMIKAWA, Akio ,  MANO, Hiroyuki

IPC分类号： C07D239/95 ,  A61K31/517 ,  A61K31/53 ,  A61K31/5377 ,  A61K31/541 ,  A61P35/00 ,  A61P43/00 ,  C07D251/18 ,  C07D251/50 ,  C07D251/52 ,  C07D251/54 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12

CPC分类号： A61K31/551 ,  A61K31/517 ,  A61K31/53 ,  A61K31/5377 ,  A61K31/541 ,  C07D239/95 ,  C07D251/18 ,  C07D251/48 ,  C07D251/50 ,  C07D251/52 ,  C07D251/70 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D417/12 ,  C07D471/10 ,  C07D487/08 ,  C07D491/113 ,  C07D498/10

摘要： The present invention provides a compound which is useful as an inhibitor against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins.
As a result of extensive and intensive studies on compounds having an inhibitory effect against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins, the inventors of the present invention have found that the di(arylamino)aryl compound of the present invention has inhibitory activity against the kinase activity of EML4-ALK fusion proteins and mutant EGFR proteins. This finding led to the completion of the present invention. The compound of the present invention can be used as a pharmaceutical composition for preventing and/or treating cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive cancer, EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive lung cancer, or EML4-ALK fusion polynucleotide-positive and/or mutant EGFR polynucleotide-positive non-small cell lung cancer, etc.

摘要翻译： 本发明提供了可用作抑制EML4-ALK融合蛋白和突变型EGFR蛋白激酶活性的化合物。 作为对具有对EML4-ALK融合蛋白和突变EGFR蛋白的激酶活性具有抑制作用的化合物的广泛和深入研究的结果，本发明的发明人已经发现本发明的二（芳基氨基）芳基化合物具有 对EML4-ALK融合蛋白和突变型EGFR蛋白激酶活性的抑制活性。 这一发现导致了本发明的完成。 本发明的化合物可以用作预防和/或治疗癌症，肺癌，非小细胞肺癌，小细胞肺癌，EML4-ALK融合多核苷酸阳性和/或突变型EGFR多核苷酸的药物组合物， 阳性癌症，EML4-ALK融合多核苷酸阳性和/或突变型EGFR多核苷酸阳性肺癌或EML4-ALK融合多核苷酸阳性和/或突变型EGFR多核苷酸阳性非小细胞肺癌等。

公开(公告)号：EP2172454A1

公开(公告)日：2010-04-07

申请号：EP08791469.3

申请日：2008-07-23

申请人： Astellas Pharma Inc.

发明人： KAKEFUDA, Akio ,  KONDOH, Yutaka ,  HIRANO, Masaaki ,  KAMIKAWA, Akio ,  ENJO, Kentaro ,  FURUTANI, Takashi

IPC分类号： C07D209/08 ,  A61K31/404 ,  A61K31/4184 ,  A61K31/4439 ,  A61P5/24 ,  A61P5/28 ,  A61P5/38 ,  A61P13/08 ,  A61P15/00 ,  A61P17/00 ,  A61P17/08 ,  A61P17/10 ,  A61P17/14 ,  A61P35/00 ,  A61P43/00 ,  C07D209/12 ,  C07D235/06 ,  C07D235/10 ,  C07D235/12 ,  C07D235/26 ,  C07D401/04

CPC分类号： C07D209/08 ,  C07D209/12 ,  C07D235/06 ,  C07D235/08 ,  C07D235/10 ,  C07D235/12 ,  C07D235/18 ,  C07D235/26 ,  C07D401/04 ,  C07D401/06 ,  C07D405/04

摘要： Provided is a novel and excellent method for treating and/or preventing benign prostatic hyperplasia, prostate cancer, and the like based on selective inhibitory activity against 17βHSD type 5. It was found that an indole or benzimidazole derivative, where a nitrogen atom of the indole ring or benzimidazole ring is substituted with a phenyl group substituted with COOH, has a potent selective inhibitory activity against 17βHSD type 5 and may become an agent for treating and/or an agent for preventing a disease associated with 17βHSD type 5, such as benign prostatic hyperplasia, prostate cancer and the like, without accompanying adverse effects due to a decrease in testosterone; and the present invention has thus been competed.

摘要翻译： 本发明提供一种基于对17βHSD5型的选择性抑制活性来治疗和/或预防良性前列腺增生，前列腺癌等的新颖且优异的方法。发现吲哚或苯并咪唑衍生物，其中吲哚的氮原子 环或苯并咪唑环被取代有COOH的苯基取代，对17βHSD5型具有有效的选择性抑制活性，并可成为用于治疗和/或预防17βHSD5型相关疾病的药剂，例如良性前列腺 增生，前列腺癌等，而没有伴随睾酮降低引起的副作用; 并且因此本发明已经被竞争。

公开(公告)号：EP1932832A1

公开(公告)日：2008-06-18

申请号：EP06811388.5

申请日：2006-10-06

申请人： Astellas Pharma Inc.

发明人： SATO, Junji ,  HATTORI, Kazuyuki ,  KUBOTA, Hirokazu ,  MUNAKATA, Ryosuke ,  ASANO, Toru ,  MAEDA, Junko ,  KAWAKAMI, Masakatsu ,  KAMIKAWA, Akio

IPC分类号： C07D213/79 ,  A61K31/381 ,  A61K31/4025 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/42 ,  A61K31/425 ,  A61K31/426 ,  A61K31/427 ,  A61K31/4418 ,  A61K31/443 ,  A61K31/4436 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/4535

CPC分类号： C07D213/79 ,  C07D231/14 ,  C07D261/18 ,  C07D275/03 ,  C07D277/56 ,  C07D333/38 ,  C07D333/60 ,  C07D333/76 ,  C07D401/10 ,  C07D405/10 ,  C07D409/10 ,  C07D413/10 ,  C07D417/10

摘要： It is intended to provide an agent for treating or preventing hyperuricemia, gout, inflammatory bowel disease, diabetic nephropathy, diabetic retinopathy and so on which has a non-nucleic acid structure and exerts an excellent xanthine oxidase inhibiting action and a hypouricemic effect. It has been confirmed that a novel triarylcarboxylic acid derivative, which is characterized by having a carboxyl-substituted heteroaryl group and an aromatic ring group such as a phenyl group attached in para-position on a benzene ring and further carrying a cyano group on the same benzene ring, has a potent xanthine oxidase inhibiting action and a hypouricemic effect. Thus, it is found out that this compound is appropriately usable as an agent for treating or preventing hyperuricemia, gout, inflammatory bowel disease, diabetic nephropathy, diabetic retinopathy and so on.

摘要翻译： 旨在提供用于治疗或预防高尿酸血症，痛风，炎性肠病，糖尿病性肾病，糖尿病性视网膜病等的具有非核酸结构并且发挥优异的黄嘌呤氧化酶抑制作用和低血糖作用的药剂。 已经证实了一种新的三芳基羧酸衍生物，其特征在于在苯环的对位具有羧基取代的杂芳基和诸如苯基的芳环基团，并且在其上还携带有氰基 苯环，具有强效的黄嘌呤氧化酶抑制作用和低氧效应。 由此可知，该化合物适合用作治疗或预防高尿酸血症，痛风，炎症性肠病，糖尿病性肾病，糖尿病性视网膜病等的药剂。

公开(公告)号：EP1990335A1

公开(公告)日：2008-11-12

申请号：EP07737642.4

申请日：2007-03-01

申请人： Astellas Pharma Inc.

发明人： NIIMI, Tatsuya ,  KAMIKAWA, Akio ,  AMANO, Yasushi ,  YAMAGUCHI, Tomohiko ,  SUZUMURA, Kenichi ,  ENJO, Kentaro ,  FURUTANI, Takashi ,  KAKEFUDA, Akio ,  KONDOH, Yutaka ,  HIRANO, Masaaki

IPC分类号： C07D209/42 ,  A61K31/404 ,  A61K31/407 ,  A61K31/4155 ,  A61K31/4178 ,  A61K31/4245 ,  A61K31/427 ,  A61K31/428 ,  A61K31/433 ,  A61K31/4439 ,  A61K31/538 ,  A61P5/24 ,  A61P5/38 ,  A61P13/08 ,  A61P15/00 ,  A61P15/08 ,  A61P17/08 ,  A61P17/10 ,  A61P17/14 ,  A61P35/00

CPC分类号： C07D209/08 ,  C07D401/12 ,  C07D403/12 ,  C07D405/12 ,  C07D409/12 ,  C07D409/14 ,  C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D471/04 ,  C07D513/04

摘要： To provide a novel and excellent method for treating and/or preventing prostatic cancer, benign prostatic hyperplasia, acne, seborrhea, hirsutism, baldness, alopecia, precocious puberty, adrenal hypertrophy, polycystic ovary syndrome, breast cancer, lung cancer, endometriosis, leiomyoma and the like based on selective inhibitory activity against 17βHSD type 5.
It was found that an N-sulfonylindole derivative, where the indole ring is substituted by a carboxy group, a carboxy-substituted lower alkyl group or a carboxy-substituted lower alkenyl group at its carbon atom, has potent selective inhibitory activity against 17βHSD type 5 and may become a therapeutic agent and/or preventive agent for benign prostatic hyperplasia, prostatic cancer and the like without accompanying adverse drug reactions due to a decrease in testosterone; and the present invention has thus been completed.

摘要翻译： 提供治疗和/或预防前列腺癌，良性前列腺增生，痤疮，皮脂溢，多毛症，秃发，脱发，早熟性青春期，肾上腺肥大，多囊卵巢综合征，乳腺癌，肺癌，子宫内膜异位症，平滑肌瘤和 其基于对17,2HSD型5的选择性抑制活性。发现其吲哚环被羧基取代的N-磺基吲哚衍生物，羧基取代的低级烷基或羧基取代的低级烯基 碳原子对17,2HSD 5型具有有效的选择性抑制活性，并且可能成为由于睾丸激素降低引起的伴有不良药物反应的良性前列腺增生，前列腺癌等的治疗剂和/或预防剂; 从而完成了本发明。

公开(公告)号：EP1932832B1

公开(公告)日：2010-12-01

申请号：EP06811388.5

申请日：2006-10-06

申请人： Astellas Pharma Inc.

发明人： SATO, Junji ,  HATTORI, Kazuyuki ,  KUBOTA, Hirokazu ,  MUNAKATA, Ryosuke ,  ASANO, Toru ,  MAEDA (WATANABE), Junko. ,  KAWAKAMI, Masakatsu ,  KAMIKAWA, Akio

IPC分类号： C07D213/79 ,  A61K31/381 ,  A61K31/4025 ,  A61K31/404 ,  A61K31/415 ,  A61K31/4155 ,  A61K31/42 ,  A61K31/425 ,  A61K31/426 ,  A61K31/427 ,  A61K31/4418 ,  A61P19/06

CPC分类号： C07D213/79 ,  C07D231/14 ,  C07D261/18 ,  C07D275/03 ,  C07D277/56 ,  C07D333/38 ,  C07D333/60 ,  C07D333/76 ,  C07D401/10 ,  C07D405/10 ,  C07D409/10 ,  C07D413/10 ,  C07D417/10

摘要： It is intended to provide a remedy or a preventive for hyperuricemia, gout, inflammatory bowel disease, diabetic nephropathy, diabetic retinitis and so on which has a non-nucleic acid structure and exerts an excellent xanthine oxidase inhibitory effect and a uric acid level-lowering effect. It has been confirmed that a novel triarylcarboxlic acid derivative, which is characterized by having a carboxyl-substituted heteroaryl group and an aromatic ring group such as a phenyl group attached in para-position on a benzene ring and further carrying a cyano group on the same benzene ring, has a potent xanthine oxidase inhibitory effect and a uric acid level-lowering effect. Thus, it is found out that this compound is appropriately usable as a remedy or a preventive for hyperuricemia, gout, inflammatory bowel disease, diabetic nephropathy, diabetic retinitis and so on.

摘要翻译： 其目的在于提供具有非核酸结构并发挥出色的黄嘌呤氧化酶抑制作用和尿酸水平降低作用的高尿酸血症，痛风，炎性肠病，糖尿病性肾病，糖尿病性视网膜炎等的治疗或预防 影响。 已经证实了一种新的三芳基羧酸衍生物，其特征在于在苯环的对位具有羧基取代的杂芳基和诸如苯基的芳环基团，并且在其上还带有氰基 苯环，具有强效的黄嘌呤氧化酶抑制作用和尿酸水平降低作用。 因此，发现该化合物适合用作高尿酸血症，痛风，炎性肠病，糖尿病肾病，糖尿病性视网膜炎等的治疗或预防。

公开(公告)号：EP2181990A1

公开(公告)日：2010-05-05

申请号：EP08828181.1

申请日：2008-08-28

申请人： Astellas Pharma Inc.

发明人： KAKEFUDA, Akio ,  WATANABE, Kazushi ,  KAMIKAWA, Akio ,  ENJO, Kentaro ,  FURUTANI, Takashi ,  YASUDA, Minoru

IPC分类号： C07D401/06 ,  A61K31/4465 ,  A61P13/08 ,  A61P35/00 ,  C07D401/14 ,  C07D491/056

CPC分类号： C07D401/06

摘要： As a result of studies on compounds having a selective inhibitory activity against 17βHSD type 5, the present inventors have confirmed that a {1-[(indol-2-yl)carbonyl]piperidyl}alkanol derivative has a potent selective inhibitory activity against 17βHSD type 5. The invention has been completed based on these findings. The compound of the present invention can be used as an agent for treating and/or an agent for preventing diseases associated with 17βHSD type 5, such as benign prostatic hyperplasia and prostate cancer, without accompanying adverse effects due to a decrease in testosterone.

摘要翻译： 作为对17,2HSD 5型选择性抑制活性的化合物的研究结果，本发明人证实{1 - [（吲哚-2-基）羰基]哌啶基}链烷醇衍生物对17,2HSD型具有有效的选择性抑制活性 基于这些发现完成了本发明。 本发明的化合物可以用作治疗和/或预防与17,2HSD 5型相关的疾病的药物，例如良性前列腺增生和前列腺癌，而不伴随睾丸激素降低引起的不良反应。