公开(公告)号：US20170240538A1

公开(公告)日：2017-08-24

申请号：US15501888

申请日：2015-08-10

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Scott D. Larsen ,  Kristoff Homan ,  Helen Waldschmidt ,  John J.G. Tesmer

IPC: C07D413/14 ,  C07D405/14 ,  C07D403/14 ,  C07D401/14 ,  C07D403/12

CPC classification number: C07D413/14 ,  C07D401/14 ,  C07D403/12 ,  C07D403/14 ,  C07D405/14

Abstract: Disclosed herein are novel GRK2 inhibitors and methods for their use in treating or preventing heart disease, such as cardiac failure, cardiac hypertrophy, and hypertension. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salt thereof: wherein the substituents are as described.

公开(公告)号：US20150250769A1

公开(公告)日：2015-09-10

申请号：US14642203

申请日：2015-03-09

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  BOARD OF TRUSTEES OF MICHIGAN STATE UNIVERSITY

Inventor： Scott D. Larsen ,  Jessica L. Bell ,  Richard Neubig ,  Kim Hutchings

IPC: A61K31/4245 ,  A61K45/06

CPC classification number: A61K31/4245 ,  A61K31/415 ,  A61K31/4184 ,  A61K31/4196 ,  A61K31/422 ,  A61K31/433 ,  A61K31/4439 ,  A61K31/513 ,  A61K45/06 ,  Y02A50/401 ,  Y02A50/475 ,  Y02A50/481 ,  A61K2300/00

Abstract: The present disclosure relates to methods, compositions, and kits for the inhibition of signaling by members of the Rho GTPase family. Specifically, the disclosure relates to methods, compositions and kits for the inhibition of RhoA and/or RhoC transcriptional signaling and action of the transcription co-factors MRTF-A and/or MRTF-B. The disclosure finds use in treatment of Rho-mediated disease states (e.g., tumor metastasis and fibrosis), Rho-mediated biological conditions, and in cell signaling research.

Abstract translation: 本公开涉及用于抑制Rho GTP酶家族的信号传导的方法，组合物和试剂盒。 具体地，本公开涉及用于抑制RhoA和/或RhoC转录信号传导和转录辅因子MRTF-A和/或MRTF-B的作用的方法，组合物和试剂盒。 该公开内容用于治疗Rho介导的疾病状态（例如肿瘤转移和纤维化），Rho介导的生物学条件和细胞信号传导研究。

公开(公告)号：US10662183B2

公开(公告)日：2020-05-26

申请号：US14934769

申请日：2015-11-06

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  BOARD OF TRUSTEES OF MICHIGAN STATE UNIVERSITY

Inventor： Scott D. Larsen ,  Richard Neubig ,  Andrew Haak ,  Kim Hutchings ,  Walajapet Rajeswaran ,  Dinesh Khanna ,  Erika Mathes Lisabeth

IPC: C07D211/06 ,  C07D211/60 ,  C07D417/14 ,  C07D405/10 ,  C07D409/10 ,  C07D405/14 ,  C07D401/10 ,  C07D401/06 ,  C07D417/06 ,  C07D413/14 ,  C07D417/10 ,  C07D413/06 ,  C07D405/06

Abstract: Disclosed herein are inhibitors of gene transcription mediated by myocardin-related transcription factor and serum response factor, or both myocardin-related transcription factor and serum response factor (“MRTF/SRF”), and methods for their use in treating or preventing cancer and fibrosis. In particular, disclosed herein are compounds of Formula (I) and Formula (II), and pharmaceutically acceptable salts thereof: wherein the substituents are as described.

公开(公告)号：US20190255055A1

公开(公告)日：2019-08-22

申请号：US16311533

申请日：2017-06-20

Applicant: The Regents of the University of Michigan ,  Indiana University Research and Technology Corporation

Inventor： Scott D. Larsen ,  Brandt C. Huddle ,  Kun Yang ,  Ronald Buckanovich ,  Thomas Hurley

IPC: A61K31/519 ,  A61P31/00 ,  A61P35/00 ,  A61K45/06 ,  C07D487/04

Abstract: This invention is in the field of medicinal chemistry. In particular, the invention relates to a new class of small-molecules having a thiopyrimidinone structure which function as inhibitors of ALDH protein, and their use as therapeutics for the treatment of cancer and other diseases.

公开(公告)号：US10202340B2

公开(公告)日：2019-02-12

申请号：US15546320

申请日：2016-02-01

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Scott D. Larsen ,  Akira Abe ,  Liming Shu ,  Michael William Wilson ,  Richard F. Keep ,  Duxin Sun ,  James A. Shayman

IPC: A61K31/4015 ,  C07D207/06 ,  C07D263/20 ,  C07D207/04 ,  C07D263/24 ,  C07D205/04 ,  C07D207/09 ,  C07D207/10 ,  C07D295/125 ,  C07D295/13

Abstract: Glucosylceramide synthase inhibitors and compositions containing the same are disclosed. Methods of using the glucosylceramide synthase inhibitors in the treatment of diseases and conditions wherein inhibition of glucosylceramide synthase provides a benefit, like Gaucher disease and Fabry disease, also are disclosed.

公开(公告)号：US11220479B2

公开(公告)日：2022-01-11

申请号：US17076852

申请日：2020-10-22

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN

Inventor： Scott D. Larsen ,  James A. Shayman ,  Kim Hutchings ,  Neil Moss ,  Qin Jiang ,  Nicholas Mayhew ,  Emily Freeman ,  Zohreh Sajjadi Hashemi

IPC: C07D205/04 ,  C07D207/09 ,  C07D405/12

Abstract: Glucosylceramide synthase inhibitors and compositions containing the same are disclosed. Methods of using the glucosylceramide synthase inhibitors in the treatment of diseases and conditions wherein inhibition of glucosylceramide synthase provides a benefit, like Gaucher disease and Fabry disease, also are disclosed.

公开(公告)号：US10851072B2

公开(公告)日：2020-12-01

申请号：US16376349

申请日：2019-04-05

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  BOARD OF TRUSTEES OF MICHIGAN STATE UNIVERSITY

Inventor： Scott D. Larsen ,  Richard Neubig ,  Kim Hutchings ,  Dylan Kahl ,  Erika Mathes Lisabeth

IPC: C07D271/113 ,  C07D271/06 ,  C07D413/12 ,  A61P35/00

Abstract: Disclosed herein are inhibitors of Rho/MRTF/SRF-mediated gene transcription, and methods for their use in treating or preventing diseases such as cancer and fibrosis. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof: wherein the substituents are as described.

公开(公告)号：US20190308947A1

公开(公告)日：2019-10-10

申请号：US16376349

申请日：2019-04-05

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  BOARD OF TRUSTEES OF MICHIGAN STATE UNIVERSITY

Inventor： Scott D. Larsen ,  Richard Neubig ,  Kim Hutchings ,  Dylan Kahl ,  Erika Mathes Lisabeth

IPC: C07D271/113 ,  C07D413/12

Abstract: Disclosed herein are inhibitors of Rho/MRTF/SRF-mediated gene transcription, and methods for their use in treating or preventing diseases such as cancer and fibrosis. In particular, disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof: wherein the substituents are as described.

公开(公告)号：US09504688B2

公开(公告)日：2016-11-29

申请号：US14397798

申请日：2013-05-02

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  THE CURATORS OF THE UNIVERSITY OF MISSOURI

Inventor： David Ginsburg ,  Scott D. Larsen ,  Bryan Yestrepsky ,  Hongmin Sun

IPC: C07D239/70 ,  C07D487/04 ,  C07D487/10 ,  A61L31/08 ,  A61L31/16 ,  A61K31/517 ,  A61K45/06 ,  A61K31/505 ,  A01N43/54 ,  A01N43/90 ,  A01N43/84 ,  A61K31/5377 ,  C07D239/56 ,  C07D471/10 ,  C07D491/107

CPC classification number: A61K31/517 ,  A01N43/54 ,  A01N43/84 ,  A01N43/90 ,  A61K31/505 ,  A61K31/5377 ,  A61K45/06 ,  A61L31/08 ,  A61L31/16 ,  A61L2300/404 ,  C07D239/56 ,  C07D239/70 ,  C07D471/10 ,  C07D487/10 ,  C07D491/107

Abstract: The present invention relates to chemical compounds, methods for their discovery, and their therapeutic and research use. In particular, the present invention provides compounds as therapeutic agents against bacterial infections (e.g., biofilms).

Abstract translation: 本发明涉及化学化合物，其发现方法及其治疗和研究用途。 特别地，本发明提供了作为抗细菌感染（例如生物膜）的治疗剂的化合物。

公开(公告)号：US20160145251A1

公开(公告)日：2016-05-26

申请号：US14934769

申请日：2015-11-06

Applicant: THE REGENTS OF THE UNIVERSITY OF MICHIGAN ,  BOARD OF TRUSTEES OF MICHIGAN STATE UNIVERSITY

Inventor： Scott D. Larsen ,  Richard Neubig ,  Andrew Haak ,  Kim Hutchings ,  Walajapet Rajeswaran

IPC: C07D417/14 ,  C07D409/10 ,  C07D405/14 ,  C07D401/10 ,  C07D211/60 ,  C07D417/06 ,  C07D413/14 ,  C07D417/10 ,  C07D413/06 ,  C07D405/06 ,  C07D405/10 ,  C07D401/06

Abstract: Disclosed herein are inhibitors of gene transcription mediated by myocardin-related transcription factor and serum response factor, or both myocardin-related transcription factor and serum response factor (“MRTF/SRF”), and methods for their use in treating or preventing cancer and fibrosis. In particular, disclosed herein are compounds of Formula (I) and Formula (II), and pharmaceutically acceptable salts thereof: wherein the substituents are as described.

Abstract translation: 本文公开了由心肌素相关转录因子和血清响应因子或心肌素相关转录因子和血清反应因子（“MRTF / SRF”）介导的基因转录抑制剂及其用于治疗或预防癌症和纤维化的方法 。 特别地，本文公开了式（I）和式（II）的化合物及其药学上可接受的盐：其中取代基如所述。