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公开(公告)号：US10259821B2
公开(公告)日：2019-04-16
申请号：US15873571
申请日：2018-01-17
发明人： Ippei Sato , Takashi Kamikubo , Masanori Miura , Yuji Matsushima , Hiroaki Tanaka , Yasuhiro Shiina , Susumu Yamaki , Tomoyuki Saito , Hiroshi Kiyohara , Munemichi Ohe , Kayoko Mihara , Bradley Paul Morgan , Fady Malik , Scott Emile Collibee , Luke Ashcraft , Pu-Ping Lu , Jeffrey Michael Warrington , Marc Garard
IPC分类号： C07D491/20 , C07D491/107 , C07D471/04 , C07D471/10 , C07D217/24 , C07D217/26
摘要： Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.
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公开(公告)号：US20180148458A1
公开(公告)日：2018-05-31
申请号：US15873571
申请日：2018-01-17
发明人： Ippei Sato , Takashi Kamikubo , Masanori Miura , Yuji Matsushima , Hiroaki Tanaka , Yasuhiro Shiina , Susumu Yamaki , Tomoyuki Saito , Hiroshi Kiyohara , Munemichi Ohe , Kayoko Mihara , Bradley Paul Morgan , Fady Malik , Scott Emile Collibee , Luke Ashcraft , Pu-Ping Lu , Jeffrey Michael Warrington , Marc Garard
IPC分类号： C07D491/20 , C07D491/107 , C07D471/04 , C07D471/10 , C07D217/24 , C07D217/26
CPC分类号： C07D491/20 , C07D217/24 , C07D217/26 , C07D471/04 , C07D471/10 , C07D491/107
摘要： Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.
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公开(公告)号：US09914741B2
公开(公告)日：2018-03-13
申请号：US15429738
申请日：2017-02-10
发明人： Ippei Sato , Takashi Kamikubo , Masanori Miura , Yuji Matsushima , Hiroaki Tanaka , Yasuhiro Shiina , Susumu Yamaki , Tomoyuki Saito , Hiroshi Kiyohara , Munemichi Ohe , Kayoko Mihara , Bradley Paul Morgan , Fady Malik , Scott Emile Collibee , Luke Ashcraft , Pu-Ping Lu , Jeffrey Michael Warrington , Marc Garard
IPC分类号： C07D491/20 , C07D471/10 , C07D471/04 , C07D217/26 , C07D491/107 , C07D217/24
CPC分类号： C07D491/20 , C07D217/24 , C07D217/26 , C07D471/04 , C07D471/10 , C07D491/107
摘要： Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.
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公开(公告)号：US10689393B2
公开(公告)日：2020-06-23
申请号：US16291481
申请日：2019-03-04
发明人： Ippei Sato , Takashi Kamikubo , Masanori Miura , Yuji Matsushima , Hiroaki Tanaka , Yasuhiro Shiina , Susumu Yamaki , Tomoyuki Saito , Hiroshi Kiyohara , Munemichi Ohe , Kayoko Mihara , Bradley Paul Morgan , Fady Malik , Scott Emile Collibee , Luke Ashcraft , Pu-Ping Lu , Jeffrey Michael Warrington , Marc Garard
IPC分类号： C07D491/20 , C07D471/10 , C07D217/26 , C07D491/107 , C07D471/04 , C07D217/24 , A61P21/00
摘要： Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.
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公开(公告)号：US20190194220A1
公开(公告)日：2019-06-27
申请号：US16291481
申请日：2019-03-04
发明人： Ippei Sato , Takashi Kamikubo , Masanori Miura , Yuji Matsushima , Hiroaki Tanaka , Yasuhiro Shiina , Susumu Yamaki , Tomoyuki Saito , Hiroshi Kiyohara , Munemichi Ohe , Kayoko Mihara , Bradley Paul Morgan , Fady Malik , Scott Emile Collibee , Luke Ashcraft , Pu-Ping Lu , Jeffrey Michael Warrington , Marc Garard
IPC分类号： C07D491/20 , C07D471/10 , C07D217/26 , C07D491/107 , C07D217/24 , C07D471/04
摘要： Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.
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公开(公告)号：US12077519B2
公开(公告)日：2024-09-03
申请号：US18521400
申请日：2023-11-28
发明人： Hideyuki Watanabe , Takashi Kamikubo , Akio Kamikawa , Takuya Washio , Yohei Seki , Keiichiro Okuyama , Osamu Ikeda , Hiroshi Tomiyama , Yoshinori Iwai , Akihiko Nakamura , Kozo Miyasaka
IPC分类号： C07D401/12 , A61K31/454 , A61K31/4545 , A61K31/496 , A61K31/501 , A61K31/519 , A61P35/00 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/14 , C07D413/04 , C07D413/14 , C07D487/04
CPC分类号： C07D401/12 , A61K31/454 , A61K31/4545 , A61K31/496 , A61K31/501 , A61K31/519 , A61P35/00 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/14 , 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：US20240101532A1
公开(公告)日：2024-03-28
申请号：US18521400
申请日：2023-11-28
发明人： Hideyuki Watanabe , Takashi Kamikubo , Akio Kamikawa , Takuya Washio , Yohei Seki , Keiichiro Okuyama , Osamu Ikeda , Hiroshi Tomiyama , Yoshinori Iwai , Akihiko Nakamura , Kozo Miyasaka
IPC分类号： C07D401/12 , A61K31/454 , A61K31/4545 , A61K31/496 , A61K31/501 , A61K31/519 , A61P35/00 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/14 , C07D413/04 , C07D413/14 , C07D487/04
CPC分类号： C07D401/12 , A61K31/454 , A61K31/4545 , A61K31/496 , A61K31/501 , A61K31/519 , A61P35/00 , C07D401/14 , C07D403/12 , C07D403/14 , C07D405/14 , 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：US20240043403A1
公开(公告)日：2024-02-08
申请号：US18254829
申请日：2021-11-29
发明人： Hideyuki Watanabe , Takashi Kamikubo , Akio Kamikawa , Takuya Washio , Yohei Seki , Keiichiro Okuyama , Osamu Ikeda , Hiroshi Tomiyama , Yoshinori Iwai , Akihiko Nakamura , Kozo Miyasaka
IPC分类号： C07D401/12 , A61P35/00 , A61K31/454 , C07D487/04 , A61K31/4545 , A61K31/496 , A61K31/501 , C07D403/14 , C07D413/14 , C07D401/14 , C07D403/12 , C07D405/14 , C07D413/04 , A61K31/519
CPC分类号： C07D401/12 , A61P35/00 , A61K31/454 , C07D487/04 , A61K31/4545 , A61K31/496 , A61K31/501 , C07D403/14 , C07D413/14 , C07D401/14 , C07D403/12 , C07D405/14 , C07D413/04 , A61K31/519
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：US11479561B2
公开(公告)日：2022-10-25
申请号：US16871532
申请日：2020-05-11
发明人： Ippei Sato , Takashi Kamikubo , Masanori Miura , Yuji Matsushima , Hiroaki Tanaka , Yasuhiro Shiina , Susumu Yamaki , Tomoyuki Saito , Hiroshi Kiyohara , Munemichi Ohe , Kayoko Mihara , Bradley Paul Morgan , Fady Malik , Scott Emile Collibee , Luke Ashcraft , Pu-Ping Lu , Jeffrey Michael Warrington , Marc Garard
IPC分类号： A61K31/4747 , A61K31/472 , C07D491/20 , C07D491/107 , C07D217/24 , C07D471/04 , C07D217/26 , C07D471/10 , A61P21/00
摘要： Novel tetrahydroisoquinoline derivative compounds are disclosed herein that may be used as an active ingredient for a pharmaceutical composition, and in particular, for a pharmaceutical composition useful for preventing or treating a disease or condition responsive to modulation of the contractility of the skeletal sarcomere. This may be accomplished, for example, by modulation of the troponin complex of the fast skeletal muscle sarcomere through one or more of fast skeletal myosin, actin, tropomyosin, troponin C, troponin I, and troponin T, and fragments and isoforms thereof. The tetrahydroisoquinoline derivative compounds can thus be used as an agent for preventing or treating 1) neuromuscular disorders, 2) disorders of voluntary muscle, 3) CNS disorders in which muscle weakness, atrophy, and fatigue are prominent symptoms, 4) muscle symptoms stemming from systemic disorders, and 5) dysfunctions of pelvic floor and urethral/anal sphincter muscle.
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