公开(公告)号：US20230192594A1

公开(公告)日：2023-06-22

申请号：US18170048

申请日：2023-02-16

申请人： The United States of America, as Represented by the Secretary, Department of Health ,  University of Maryland, Baltimore

发明人： Craig Thomas ,  Carlos Zarate ,  Ruin Moaddel ,  Todd Gould ,  Panos Zanos ,  Patrick Morris

IPC分类号： C07C225/20 ,  C07C221/00 ,  C07C269/06

CPC分类号： C07C225/20 ,  C07C221/00 ,  C07C269/06 ,  C07B2200/13 ,  C07C2601/14 ,  C07C2601/16

摘要： The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketam-ine (HNK) includes preparation of (R)-norket-amine via chiral resolution from racemic norketamine via a chiral resolution with L-pyro-glutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hy-droxynorketamine hydrochloride salts.

公开(公告)号：US11897875B2

公开(公告)日：2024-02-13

申请号：US17883734

申请日：2022-08-09

申请人： UNIVERSITY OF MARYLAND, BALTIMORE ,  THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

发明人： Scott Thompson ,  Adam Van Dyke ,  Craig Thomas ,  Patrick Morris

IPC分类号： C07D417/14 ,  A61P25/24 ,  C07D261/08 ,  C07D413/12 ,  C07D413/14 ,  A61K9/19 ,  A61K45/06

CPC分类号： C07D417/14 ,  A61P25/24 ,  C07D261/08 ,  C07D413/12 ,  C07D413/14 ,  A61K9/19 ,  A61K45/06 ,  C07B2200/05

摘要： The present invention relates to novel alpha5 subunit-selective negative allosteric modulators of GABAA receptors that have been deuterated to improve their medicinal properties by prolonging their half-lives, rendering them useful as fast-acting pharmaceutical treatments for depression related disorders.

公开(公告)号：US11613514B2

公开(公告)日：2023-03-28

申请号：US17155162

申请日：2021-01-22

申请人： THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES ,  University of Maryland, Baltimore

发明人： Craig Thomas ,  Carlos Zarate ,  Ruin Moaddel ,  Todd Gould ,  Panos Zanos ,  Patrick Morris

IPC分类号： C07C225/20 ,  C07C221/00 ,  C07C269/06

摘要： The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

公开(公告)号：US11459320B2

公开(公告)日：2022-10-04

申请号：US16642445

申请日：2018-08-28

申请人： UNIVERSITY OF MARYLAND, BALTIMORE ,  THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

发明人： Scott Thompson ,  Adam Van Dyke ,  Craig Thomas ,  Patrick Morris

IPC分类号： C07D417/14 ,  A61P25/24 ,  C07D261/08 ,  C07D413/12 ,  A61K9/19 ,  A61K45/06

摘要： The present invention relates to novel alpha5 subunit-selective negative allosteric modulators of GABAA receptors that have been deuterated to improve their medicinal properties by prolonging their half-lives, rendering them useful as fast-acting pharmaceutical treatments for depression related disorders.

公开(公告)号：US20220396572A1

公开(公告)日：2022-12-15

申请号：US17883734

申请日：2022-08-09

申请人： UNIVERSITY OF MARYLAND, BALTIMORE ,  THE UNITED STATES OF AMERICA, AS REPRESENTED BY THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVIC

发明人： Scott Thompson ,  Adam Van Dyke ,  Craig Thomas ,  Patrick Morris

IPC分类号： C07D417/14 ,  A61P25/24 ,  C07D413/14

摘要： The present invention relates to novel alpha5 subunit-selective negative allosteric modulators of GABAA receptors that have been deuterated to improve their medicinal properties by prolonging their half-lives, rendering them useful as fast-acting pharmaceutical treatments for depression related disorders.

公开(公告)号：US20150374697A1

公开(公告)日：2015-12-31

申请号：US14730707

申请日：2015-06-04

申请人： The United States of America, as Represented by the Secretary, Department of Health and Human Serv ,  The Rockefeller University ,  Icahn School of Medicine at Mount Sinai

发明人： Barry S. Coller ,  Craig Thomas ,  Marta Filizola ,  Joshua McCoy ,  Wenwei Huang ,  Min Shen

IPC分类号： A61K31/519 ,  A61K45/06

CPC分类号： A61K31/519 ,  A61K31/497 ,  A61K45/06 ,  C07D487/04 ,  C07D513/04 ,  A61K2300/00

摘要： The present invention relates to compounds and compositions useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.

摘要翻译： 本发明涉及可用于抑制和/或减少血小板沉积，粘附和/或聚集的化合物和组合物。 本发明还涉及用于治疗或预防血栓形成障碍的方法，包括中风，心肌梗死，不稳定型心绞痛，外周血管疾病，血管成形术或支架放置后的突然闭合以及血管手术导致的血栓形成。

公开(公告)号：US10919842B2

公开(公告)日：2021-02-16

申请号：US16088371

申请日：2017-03-27

申请人： The United States of America, As Represented by the Secretary, Department of Health and Human Services ,  University of Maryland

发明人： Craig Thomas ,  Carlos Zarate ,  Ruin Moaddel ,  Todd Gould ,  Panos Zanos ,  Patrick Morris

IPC分类号： C07C225/20 ,  C07C221/00 ,  C07C269/06

摘要： The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

公开(公告)号：US20190135732A1

公开(公告)日：2019-05-09

申请号：US16088371

申请日：2017-03-27

申请人： The United States of America, As Represented by the Secretary, Department of Health and Human Serv ,  University of Maryland

发明人： Craig Thomas ,  Carlos Zarate ,  Ruin Moaddel ,  Todd Gould ,  Panos Zanos ,  Patrick Morris

IPC分类号： C07C225/20 ,  C07C221/00

摘要： The disclosure provides a method for synthesizing free base forms of (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine. In an embodiment synthesis of (2R,6R)-hydroxynorketamine (HNK) includes preparation of (R)-norketamine via chiral resolution from racemic norketamine via a chiral resolution with L-pyroglutamic acid. The disclosure also provided crystal forms of the corresponding (2R,6R)-hydroxynorketamine (HNK) and (2S,6S)-hydroxynorketamine hydrochloride salts.

公开(公告)号：US09532989B2

公开(公告)日：2017-01-03

申请号：US14730707

申请日：2015-06-04

申请人： The United States of America, as Represented by the Secretary, Department of Health and Human Services ,  The Rockefeller University ,  Icahn School of Medicine at Mount Sinai

发明人： Barry S. Coller ,  Craig Thomas ,  Marta Filizola ,  Joshua McCoy ,  Wenwei Huang ,  Min Shen

IPC分类号： A01N43/90 ,  A61K31/519 ,  C07D487/04 ,  A61K31/497 ,  A61K45/06 ,  C07D513/04

CPC分类号： A61K31/519 ,  A61K31/497 ,  A61K45/06 ,  C07D487/04 ,  C07D513/04 ,  A61K2300/00

摘要： The present invention relates to compounds of Formula P-I where the variables (e.g. R1, Y, A, R1, Ra, Ra′, Rb, Rb′, Rc, Rc′, Rd, Rd′, Re, or Re′) and compositions useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.

摘要翻译： 本发明涉及可用于抑制和/或减少血小板沉积，粘附和/或聚集的化合物和组合物。 本发明还涉及用于治疗或预防血栓形成障碍的方法，包括中风，心肌梗死，不稳定型心绞痛，外周血管疾病，血管成形术或支架放置后的突然闭合以及血管手术导致的血栓形成。

公开(公告)号：US09303044B2

公开(公告)日：2016-04-05

申请号：US14372488

申请日：2013-01-16

申请人： The Rockefeller University ,  The United States of America, as Represented by the Secretary, Department of Health and Human Services ,  Mount Sinai School of Medicine, Office of Technology and Business Development

发明人： Barry S. Coller ,  Craig Thomas ,  Marta Filizola ,  Joshua McCoy ,  Wenwei Huang ,  Min Shen ,  Jian-Kang Jiang

IPC分类号： A01N43/90 ,  A61K31/519 ,  C07D471/00 ,  C07D487/00 ,  C07D491/00 ,  C07D513/04 ,  A61K45/06 ,  A61K31/436 ,  A61K31/337 ,  A61K31/4353 ,  A61K31/727 ,  A61L31/02 ,  A61L31/10 ,  A61L31/16

CPC分类号： C07D513/04 ,  A61K31/337 ,  A61K31/4353 ,  A61K31/436 ,  A61K31/519 ,  A61K31/727 ,  A61K45/06 ,  A61L31/022 ,  A61L31/10 ,  A61L31/16 ,  A61L2300/416 ,  A61L2300/42 ,  A61L2300/45 ,  A61K2300/00

摘要： The present invention relates to compounds and compositions of Formula P useful for inhibiting and/or reducing platelet deposition, adhesion and/or aggregation. The definitions of variables A, B, R2, R3, R4, Ra, Ra′, Rb, Rb′, Rc, Rd, Rd′, Re, and Re′ are provided in the disclosure. The present invention further relates to methods for the treatment or prophylaxis of thrombotic disorders, including stroke, myocardial infarction, unstable angina, peripheral vascular disease, abrupt closure following angioplasty or stent placement and thrombosis as a result of vascular surgery.

摘要翻译： 本发明涉及用于抑制和/或减少血小板沉积，粘附和/或聚集的式P化合物和组合物。 在本公开中提供了变量A，B，R2，R3，R4，Ra，Ra'，Rb，Rb'，Rc，Rd，Rd'，Re和Re'的定义。 本发明还涉及用于治疗或预防血栓形成障碍的方法，包括中风，心肌梗死，不稳定型心绞痛，外周血管疾病，血管成形术或支架放置后的突然闭合以及血管手术导致的血栓形成。