公开(公告)号：US09642835B2

公开(公告)日：2017-05-09

申请号：US13867658

申请日：2013-04-22

Applicant: STC.UNM ,  University of Kansas

Inventor： Angela Wandinger-Ness ,  Larry Sklar ,  Zurab Surviladze ,  Tudor Oprea ,  Laurie Hudson ,  Jeffrey Aube ,  Jennifer E. Golden ,  Chad E. Schroeder ,  Denise S. Simpson ,  Julica J. Noth

IPC: A61K31/415 ,  A61K45/06 ,  C07D231/06 ,  A61K31/403 ,  A61K31/407

CPC classification number: A61K31/407 ,  A61K31/403 ,  A61K31/415 ,  A61K45/06 ,  C07D231/06 ,  C12Q1/6886 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N33/573 ,  Y02A50/473 ,  Y02A50/486 ,  A61K2300/00

Abstract: The present invention relates to molecules which function as selective modulators (i.e., inhibitors and agonists, preferably inhibitors) of the Ras-homologous (Rho) family of small GTPases, in particular, Cdc42 GTPase and their use to treat diseases, for example cancers, including metastatic cancer, where Cdc42 GTPase is overexpressed or hyperactivated, genetic and acquired diseases where activation of Cdc42 GTPase plays a pivotal role (e.g., neurodegenerative diseases), rheumatoid arthritis, atherosclerosis, diabetes type I, autosomal polycystic kidney diease, cystic kidney disease, precystic kidney disease and microbial infections. Additionally, compounds according to the present invention may be used to inhibit rejection (graft host response) in transplant patients (pursuant to transplantation), to promote immunosuppression, anti-inflammatory response and to mobilize stem cell (migration) in patients in need, among others.

公开(公告)号：US09376452B2

公开(公告)日：2016-06-28

申请号：US14278468

申请日：2014-05-15

Applicant: STC.UNM ,  UNIVERSITY OF KANSAS

Inventor： Angela Wandinger-Ness ,  Larry Sklar ,  Jacob Agola ,  Zurab Surviladze ,  Jeffrey Aube ,  Jennifer Golden ,  Chad E. Schroeder ,  Denise S. Simpson

IPC: C07D495/04 ,  A61K31/381 ,  A61K45/06

CPC classification number: C07D495/04 ,  A61K31/381 ,  A61K45/06

Abstract: This invention relates to compounds and their use as inhibitors or activators of Rab7 GTPase to treat or prevent the onset of Rab 7 GTPase-associated disorders such as neuropathies, cancer, metabolic diseases of bone and lipid storage. The invention is also applicable to infectious diseases where Rab7 is inactivated or its protein-protein interactions are modulated to facilitate intracellular survival of pathogens. The compound described acts as a competitive inhibitor of nucleotide binding and as such also has utility as a scaffold for targeting other small GTPases. In one aspect, methods of treatment of the invention are used to treat or prevent the onset of hereditary sensory neuropathies such as Charcot-Marie-Tooth type 2B disease. Related pharmaceutical compositions, assays, and drug screens are also provided.

Abstract translation: 本发明涉及化合物及其作为Rab7 GTPase的抑制剂或活化剂的用途，用于治疗或预防Rab 7 GTP酶相关疾病如神经病变，癌症，骨骼和脂质储存代谢疾病的发生。 本发明也适用于Rab7灭活或其蛋白质 - 蛋白质相互作用被调节以促进病原体的细胞内存活的感染性疾病。 所描述的化合物作为核苷酸结合的竞争性抑制剂，因此也可用作靶向其他小GTP酶的支架。 一方面，本发明的治疗方法用于治疗或预防遗传性感觉神经病发作，例如Charcot-Marie-Tooth 2B型疾病。 还提供了相关的药物组合物，测定和药物筛选。

公开(公告)号：US20150197526A1

公开(公告)日：2015-07-16

申请号：US14587925

申请日：2014-12-31

Applicant: STC.UNM ,  UNIVERSITY OF KANSAS

Inventor： Richard Smith Larson ,  Larry A. Sklar ,  Bruce S. Edwards ,  Juan Jacob Strouse ,  Irena Ivnitski-Steele ,  Hydya M. Khawaja ,  Jerec Warren Ricci ,  Jeffrey Aube ,  Jennifer Elizabeth Golden ,  Tuanli Yao ,  Warren S. Weiner ,  Chad E. Schroeder

IPC: C07D487/04 ,  A61K31/4745 ,  A61K45/06 ,  A61K31/519

CPC classification number: C07D487/04 ,  A61K31/437 ,  A61K31/4745 ,  A61K31/519 ,  A61K45/06

Abstract: The present invention provides novel compounds which inhibit cancer-associated transporter proteins, methods of treating or preventing the onset of a cancer-associated transporter protein-mediated disease by administering such compounds, and pharmaceutical compositions comprising such compounds. In one embodiment, the invention provides novel pyrazolo[1,5-a]pyrimidine efflux inhibitors that are selective toward ABCG2 over ABCB1.

Abstract translation: 本发明提供抑制癌症相关转运蛋白的新型化合物，通过施用这些化合物治疗或预防癌症相关转运蛋白介导的疾病发作的方法，以及包含这些化合物的药物组合物。 在一个实施方案中，本发明提供了关于ABCB1对ABCG2有选择性的新型吡唑并[1,5-a]嘧啶外排抑制剂。

公开(公告)号：US09056111B1

公开(公告)日：2015-06-16

申请号：US13622651

申请日：2012-09-19

Applicant: STC.UNM ,  UNIVERSITY OF KANSAS

Inventor： Richard Smith Larson ,  Larry A. Sklar ,  Bruce S. Edwards ,  Juan Jacob Strouse ,  Irena Ivnitski-Steele ,  Hadya M. Khawaja ,  Jerec Warren Ricci ,  Jeffrey Aube ,  Jennifer Elizabeth Golden ,  Tuanli Yao ,  Warren S. Weiner ,  Chad E. Schroeder

IPC: A01N43/90 ,  A61K31/519 ,  C07D487/00 ,  A61K31/437 ,  C07D487/04

CPC classification number: C07D487/04 ,  A61K31/437 ,  A61K31/4745 ,  A61K31/519 ,  A61K45/06

Abstract: The present invention provides pyrazolo[1,5-a]pyrimidine compounds which inhibit cancer-associated transporter proteins, methods of treating or preventing the onset of a cancer-associated transporter protein-mediated disease by administering such compounds, and pharmaceutical compositions comprising such compounds. In one embodiment, the invention provides pyrazolo[1,5-a]pyrimidine efflux inhibitors that are selective toward ABCG2 over ABCB1. Compounds and compositions according to the present invention may be used to treat cancer, including drug resistant (DR) and multiple drug resistant (MDR) cancers.

Abstract translation: 本发明提供了抑制癌症相关转运蛋白的吡唑并[1,5-a]嘧啶化合物，通过施用这些化合物来治疗或预防与癌症相关的转运蛋白介导的疾病发作的方法，以及包含这些化合物的药物组合物 。 在一个实施方案中，本发明提供对ABCB1而言对ABCG2有选择性的吡唑并[1,5-a]嘧啶外排抑制剂。 根据本发明的化合物和组合物可用于治疗癌症，包括耐药性（DR）和多重耐药性（MDR）癌症。

公开(公告)号：US20160244457A1

公开(公告)日：2016-08-25

申请号：US15147648

申请日：2016-05-05

Applicant: UNIVERSITY OF KANSAS ,  STC.UNM

Inventor： Richard Smith Larson ,  Larry A. Sklar ,  Bruce S. Edwards ,  Juan Jacob Strouse ,  Irena lvnitski-Steele ,  Hadya M. Khawaja ,  Jerec Warren Ricci ,  Jeffrey Aube ,  Jennifer Elizabeth Golden ,  TuanIi Yao ,  Warren S. Weiner ,  Chad E. Schroeder

IPC: C07D487/04 ,  A61K31/4745 ,  A61K31/519

CPC classification number: C07D487/04 ,  A61K31/437 ,  A61K31/4745 ,  A61K31/519 ,  A61K45/06

Abstract: The present invention provides novel compounds which inhibit cancer-associated transporter proteins, methods of treating or preventing the onset of a cancer-associated transporter protein-mediated disease by administering such compounds, and pharmaceutical compositions comprising such compounds. In one embodiment, the invention provides novel pyrazolo[1,5-a]pyrimidine efflux inhibitors that are selective toward ABCG2 over ABCB1.

公开(公告)号：US10059722B2

公开(公告)日：2018-08-28

申请号：US14439373

申请日：2013-11-04

Applicant: University of Kansas ,  Cornell University

Inventor： Jeffrey Aube ,  Carl Nathan ,  Robert Smith ,  Ben S. Gold ,  Paul Hanson ,  Chunjing Liu ,  Lester Allen Mitscher ,  Maneesh Pingle ,  Frank John Schoenen

IPC: C07D501/60 ,  C07D501/16 ,  A61K31/545 ,  C07D499/44 ,  C07D277/06 ,  C07D417/12 ,  C07D513/04 ,  A61K45/06 ,  A61K31/426 ,  A61K31/427 ,  A61K31/429 ,  A61K31/43 ,  A61K31/431 ,  A61K31/4725 ,  A61K31/546

CPC classification number: C07D501/16 ,  A61K31/426 ,  A61K31/427 ,  A61K31/429 ,  A61K31/43 ,  A61K31/431 ,  A61K31/4725 ,  A61K31/545 ,  A61K31/546 ,  A61K45/06 ,  C07D277/06 ,  C07D417/12 ,  C07D499/44 ,  C07D513/04 ,  Y02A50/401 ,  Y02A50/402 ,  A61K2300/00

Abstract: This invention provides cephalosporin derivatives for killing or inhibiting the spread of microorganisms such as non-replicating Mycobacterium tuberculosis and in the treatment of infectious disease.

公开(公告)号：US20170334889A1

公开(公告)日：2017-11-23

申请号：US15672574

申请日：2017-08-09

Applicant: University of Kansas ,  The Regents of the University of Michigan ,  Wayne State University ,  Sanford-Burnham Medical Research Institute

Inventor： Jennifer E. Golden ,  Jeffrey Aube ,  Daniel P. Flaherty ,  Andrew M. Fribley ,  Randal J. Kaufman ,  Thomas D.Y. Chung ,  Anthony B. Pinkerton ,  Michael Pablo Hedrick

IPC: C07D405/12 ,  C07C303/36 ,  A61K45/06 ,  A61K31/5377 ,  A61K31/496 ,  C07D307/71 ,  A61K31/4525

Abstract: N-substituted sulfonylphenyl-5-nitrofuranyl-2-carboxamide derived compounds, which selectively activate the apoptotic, but not the adaptive arm, of the Unfolded Protein Response are provides as is their use in the treatment of diseases such as diabetes, Alzheimer's, Parkinson's, hemophilia, lysosomal storage diseases and cancer.

公开(公告)号：US09732067B2

公开(公告)日：2017-08-15

申请号：US14408736

申请日：2013-06-18

Applicant: University of Kansas ,  The Regents of the University of Michigan ,  Wayne State University ,  Sanford-Burnham Medical Research Institute

Inventor： Jennifer E. Golden ,  Jeffrey Aube ,  Daniel P. Flaherty ,  Andrew M. Fribley ,  Randal J. Kaufman ,  Thomas D. Y. Chung ,  Anthony B. Pinkerton ,  Michael Pablo Hedrick

IPC: C07D405/12 ,  C07C303/36 ,  A61K31/4525 ,  C07D307/71 ,  A61K31/496 ,  A61K31/5377 ,  A61K45/06

CPC classification number: C07D405/12 ,  A61K31/4525 ,  A61K31/496 ,  A61K31/5377 ,  A61K45/06 ,  C07C303/36 ,  C07D307/71

Abstract: N-substituted sulfonylphenyl-5-mitrofuranyl-2-carboxamide derived compounds, which selectively activate the apoptotic, but not the adaptive arm, of the Unfolded Protein Response are provided as is their use in the treatment of diseases such as diabetes, Alzheimer's, Parkinson's, hemophilia, lysosomal storage diseases and cancer.

公开(公告)号：US20170166557A1

公开(公告)日：2017-06-15

申请号：US15443232

申请日：2017-02-27

Applicant: University of Kansas ,  University of Louisville Research Foundation, Inc. ,  Southern Research Institute

Inventor： Jennifer Golden ,  Jeffrey Aube ,  Donghoon Chung ,  Chad Schroeder ,  Tuanli Yao ,  E. Lucile White ,  Nichole A. Tower

IPC: C07D409/04 ,  C07D403/12 ,  C07D239/95 ,  C07D403/06 ,  C07D401/04 ,  C07D239/91 ,  C07D239/90

CPC classification number: C07D409/04 ,  C07D239/90 ,  C07D239/91 ,  C07D239/95 ,  C07D241/06 ,  C07D401/04 ,  C07D403/06 ,  C07D403/12 ,  C07D409/12

Abstract: The present technology relates to compounds and compositions of Formulas and methods using such compounds. The compounds and compositions described herein may be used in the treatment or prophylaxis of diseases associated with an alphavirus, for example, Venezuelan equine encephalitis virus (VEEV).

公开(公告)号：US10087168B2

公开(公告)日：2018-10-02

申请号：US15443232

申请日：2017-02-27

Applicant: University of Kansas ,  University of Louisville Research Foundation, Inc. ,  Southern Research Institute

Inventor： Jennifer Golden ,  Jeffrey Aube ,  Donghoon Chung ,  Chad Schroeder ,  Tuanli Yao ,  E. Lucile White ,  Nichole A. Tower

IPC: C07D409/04 ,  C07D239/91 ,  C07D403/12 ,  C07D239/90 ,  C07D403/06 ,  C07D401/04 ,  C07D239/95

Abstract: The present technology relates to compounds and compositions of Formulas I-III and methods using such compounds. The compounds and compositions described herein may be used in the treatment or prophylaxis of diseases associated with an alphavirus, for example, Venezuelan equine encephalitis virus (VEEV).