公开(公告)号：US20250019349A1

公开(公告)日：2025-01-16

申请号：US18767363

申请日：2024-07-09

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY ,  IllExcor Therapeutics, LLC ,  KING ABDULAZIZ UNIVERSITY ,  CHILDREN'S HOSPITAL OF PHILADELPHIA (CHOP)

Inventor： Martin SAFO ,  Yan ZHANG ,  Andrew FLEISCHMAN ,  David LIGHT ,  Moustafa EL-ARABY ,  Abdelsattar OMAR ,  Osheiza ABDULMALIK

IPC: C07D213/30 ,  A61P7/06 ,  C07D239/26

Abstract: Compounds and methods for preventing and/or treating one or more symptoms of sickle cell diseases (SCD) by administering at least one of the compounds are provided. The compounds are chemically modified to increase bioavailability and activity, e.g., so that the compounds prevent adhesion and sickling of red blood cells (RBCs).

公开(公告)号：US20240208984A1

公开(公告)日：2024-06-27

申请号：US18552761

申请日：2022-03-30

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY

Inventor： Yan ZHANG

IPC: C07D489/08 ,  A61K9/19 ,  A61K31/485 ,  A61K47/55 ,  G01N33/68

CPC classification number: C07D489/08 ,  A61K9/19 ,  A61K31/485 ,  A61K47/55 ,  G01N33/6863

Abstract: Bivalent ligands which bind to MOR-CCR5 heterodimers are provided. The bivalent ligands comprise two discrete pharmacophores, naltrexone and maraviroc, linked by a spacer and bind to MOR-CCR5 heterodimers, e.g. at the surface of a cell. The bivalent ligands are useful in assays to detect MOR-CCR5 heterodimers, as therapeutic agents to prevent and/or treat diseases characterized by the presence of MOR-CCR5 heterodimers.

公开(公告)号：US20190256483A1

公开(公告)日：2019-08-22

申请号：US16318590

申请日：2017-07-24

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY

Inventor： Martin K. SAFO ,  Guoyan XU ,  Yan ZHANG ,  Osheiza ABDULMALIK

IPC: C07D307/46 ,  C07F9/655 ,  A61P7/00 ,  A61P43/00

Abstract: Prodrugs and derivatives of 5-hydoxymethyl-2-furfural (5-HMF) with protected or modified aldehyde and/or alcohol moieties are provided. The prodrugs or derivatives exhibit increased bioavailability, e.g. due to having extended half-lives in circulation. The drugs are therefore administered i) at lower doses and/or ii) less frequently than 5-HMF, while still maintaining the beneficial therapeutic effects of 5-HMF.

公开(公告)号：US20220340531A1

公开(公告)日：2022-10-27

申请号：US17846101

申请日：2022-06-22

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY ,  THE CHILDREN'S HOSPITAL OF PHILADELPHIA

Inventor： Martin K. SAFO ,  Yan ZHANG ,  Piyusha Pradeep PAGARE ,  Guoyan XU ,  Mohini GHATGE ,  Jurgen VENITZ ,  Osheiza ABDULMALIK

IPC: C07D213/80 ,  A61P7/00 ,  A61K9/00 ,  C07D213/79 ,  C07D401/04 ,  C07D409/04

Abstract: Compounds and methods for preventing and/or treating one or more symptoms of sickle cell diseases (SCD) by administering at least one of the compounds are provided. The compounds are based on vanillin which is chemically modified to increase bioavailability and activity, e.g. so that the compounds bind to the F helix of hemoglobin (Hb) and prevent adhesion of red blood cells (RBCs).

公开(公告)号：US20210002225A1

公开(公告)日：2021-01-07

申请号：US16982745

申请日：2019-03-18

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY ,  THE CHILDREN'S HOSPITAL OF PHILADELPHIA

Inventor： Martin K. SAFO ,  Yan ZHANG ,  Piyusha Pradeep PARAGE ,  Guoyan XU ,  Mohini GHATGE ,  Jurgen VENITZ ,  Osheiza ABDULMALIK

IPC: C07D213/80 ,  C07D213/79 ,  C07D401/04 ,  C07D409/04 ,  A61K9/00 ,  A61P7/00

Abstract: Compounds and methods for preventing and/or treating one or more symptoms of sickle cell diseases (SCD) by administering at least one of the compounds are provided. The compounds are based on vanillin which is chemically modified to increase bioavailability and activity, e.g. so that the compounds bind to the F helix of hemoglobin (Hb) and prevent adhesion of red blood cells (RBCs).

公开(公告)号：US20160221978A1

公开(公告)日：2016-08-04

申请号：US14913180

申请日：2014-08-21

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY

Inventor： Martin SAFO ,  Jurgen VENITZ ,  Richmond DANSO-DANQUAH ,  Tanvi DESPANDE ,  Yan ZHANG

IPC: C07D307/58 ,  C07D213/30

CPC classification number: C07D307/58 ,  C07D213/30

Abstract: The invention provides new aromatic aldehyde compounds that have greater potency in increasing the affinity of Hb for oxygen, greater potency for preventing sickling, and additional pharmacologic properties that ameliorate other symptoms of SCD. The invention further provides methods for treating SCD by providing a subject having SCD with a compound according to the invention.

Abstract translation: 本发明提供了新的芳族醛化合物，其在提高Hb对于氧气的亲和力，更好的预防镰刀效力以及改善其他SCD症状的药理学性质方面具有更大的效力。 本发明还提供了通过向本发明的化合物提供具有SCD的受试者来治疗SCD的方法。

公开(公告)号：US20240174612A1

公开(公告)日：2024-05-30

申请号：US18386724

申请日：2023-11-03

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY ,  IllExcor Therapeutics, LLC ,  KING ABDULAZIZ UNIVERSITY ,  CHILDREN'S HOSPITAL OF PHILADELPHIA (CHOP)

Inventor： Martin SAFO ,  Yan ZHANG ,  Andrew FLEISCHMAN ,  David LIGHT ,  Moustafa EL-ARABY ,  Abdelsattar OMAR ,  Osheiza ABDULMALIK

IPC: C07D213/30 ,  A61P7/06 ,  C07D239/26

CPC classification number: C07D213/30 ,  A61P7/06 ,  C07D239/26

Abstract: Compounds and methods for preventing and/or treating one or more symptoms of sickle cell diseases (SCD) by administering at least one of the compounds are provided. The compounds are chemically modified to increase bioavailability and activity, e.g., so that the compounds prevent adhesion and sickling of red blood cells (RBCs).

公开(公告)号：US20210205472A1

公开(公告)日：2021-07-08

申请号：US15998948

申请日：2017-02-17

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY

Inventor： Yan ZHANG ,  Hu YANG ,  Dana SELLEY ,  William DEWEY ,  Hamid AKBARALI

IPC: A61K47/69 ,  A61K31/485

Abstract: Provided herein are nanoparticle conjugated synthetic opioid prodrugs that target the peripheral mu opioid receptor (MOR). The prodrugs exhibit long-lived bioavailability, do not compromise the analgesic effects of opioids administered for pain relief (and in some cases can be used for pain relief), and do not induce opioid withdrawal symptoms, when their use is discontinued. Certain of the prodrugs are especially useful for the prevention and/or treatment of unwanted opioid-induced side effects such as opioid-induced constipation (OIC).

公开(公告)号：US20190308987A1

公开(公告)日：2019-10-10

申请号：US16306232

申请日：2017-05-26

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY

Inventor： Yan ZHANG ,  Dana SELLEY ,  William DEWEY ,  Hamid AKBARALI

IPC: C07D489/08 ,  A61P1/00

Abstract: Peripherally selective compounds that modulate both the mu opioid receptor (MOR) and the kappa opioid receptor (KOR) are provided. The compounds are substituted derivatives of 6p-N-heterocyclic naltrexamine (NAP) and are used in the treatment of diseases involving visceral pain such as irritable bowel syndrome (IBS), opioid induced constipation (OIC), and others.

公开(公告)号：US20190152982A1

公开(公告)日：2019-05-23

申请号：US16301765

申请日：2017-05-16

Applicant: VIRGINIA COMMONWEALTH UNIVERSITY

Inventor： Yan ZHANG ,  Dana E. SELLEY ,  William DEWEY ,  Hamid ABKARALI

IPC: C07D489/08 ,  A61P25/30 ,  A61P25/04

Abstract: Analogues of 6 α/β-naltrexamine (NAQ) are provided. The analogues are selective, reversible antagonists of the mu opioid receptor (MOR) that exhibit good blood brain barrier penetration. The compounds are used in the treatment of opioid addiction and other diseases and conditions, including for the treatment of pain.