公开(公告)号：US20250042855A1

公开(公告)日：2025-02-06

申请号：US18707244

申请日：2022-12-01

Applicant: The Johns Hopkins University ,  Lieber Institute, Inc.

Inventor： Pankaj PASRICHA ,  James BARROW ,  Pablo DE LEON ,  Yifang HUANG ,  Qian LI

IPC: C07D211/34 ,  A61K31/451 ,  A61K31/4525 ,  C07D405/06

Abstract: Compounds and method for treating a disease, condition, or disorder associated with serotonin (5-HT) signaling, including gastroenterological disorders, such as colitis, irritable bowel syndrome (IBS), constipation, diarrhea, and gastroparesis, or extra-gastrointestinal disorders, such as asthma, migraine, itching, and osteoporosis. In some aspects, the compounds inhibit serotonin/5-HIT transporter (SERT).

公开(公告)号：US12049467B2

公开(公告)日：2024-07-30

申请号：US17590404

申请日：2022-02-01

Applicant: The Johns Hopkins University ,  Lieber Institute, Inc.

Inventor： Yifang Huang ,  Pankaj Jay Pasricha ,  James C. Barrow ,  Ingrid Buchler ,  Michael Poslusney

IPC: A61K31/5517 ,  A61P1/12 ,  C07D487/04 ,  C07D487/14

CPC classification number: C07D487/04 ,  A61P1/12

Abstract: This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof, or an N-oxide thereof) of formula (I), which are positive allosteric modulators of one or more GABA-A receptors, e.g., which are peripherally restricted, positive allosteric modulators of one or more GABA-A receptors; e.g., which are positive allosteric modulators of one or more GABA-A receptors and which selectively target the peripheral nervous system and organs of the body, and which do not substantially pass through the blood-brain barrier. Said compounds are useful e.g., for the treatment of systemic diseases of the body, e.g., diseases in which modulation of one or more peripherally restricted GABA-A receptors is beneficial (e.g., diseases or disorders which are mediated by GABA-A neuronal activity. This disclosure also features pharmaceutical compositions containing the chemical entities described herein as well as methods of using same for the treatment of systemic diseases of the body.

公开(公告)号：US20230265091A1

公开(公告)日：2023-08-24

申请号：US18024407

申请日：2021-09-15

Applicant: The Johns Hopkins University ,  Lieber Institute, Inc.

Inventor： Hester Hui Liu ,  James C. Barrow ,  Marikki K. Laiho ,  Rajesh Kumar Nv ,  Pablo de Leon ,  Tony Dorado ,  Asma Begum ,  Wenjun Fan ,  Gregory Stachelek

IPC: C07D471/04

CPC classification number: C07D471/04

Abstract: This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit RNA polymerase I (Pol I). Said chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) Pol I activity contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.

公开(公告)号：US20220251090A1

公开(公告)日：2022-08-11

申请号：US17590404

申请日：2022-02-01

Applicant: The Johns Hopkins University ,  Lieber Institute, Inc.

Inventor： Yifang Huang ,  Pankaj Jay Pasricha ,  James C. Barrow ,  Ingrid Buchler ,  Michael Poslusney

IPC: C07D487/04 ,  A61P1/12

Abstract: This disclosure features chemical entities (e.g., a compound or a pharmaceutically acceptable salt thereof, or an N-oxide thereof), which are positive allosteric modulators of one or more GABA-A receptors, e.g., which are peripherally restricted, positive allosteric modulators of one or more GABA-A receptors; e.g., which are positive allosteric modulators of one or more GABA-A receptors and which selectively target the peripheral nervous system and organs of the body, and which do not substantially pass through the blood-brain barrier. Said compounds are useful e.g., for the treatment of systemic diseases of the body, e.g., diseases in which modulation of one or more peripherally restricted GABA-A receptors is beneficial (e.g., diseases or disorders which are mediated by GABA-A neuronal activity. This disclosure also features pharmaceutical compositions containing the chemical entities described herein as well as methods of using same for the treatment of systemic diseases of the body.

公开(公告)号：US20220227732A1

公开(公告)日：2022-07-21

申请号：US17256781

申请日：2019-07-09

Applicant: Lieber Institute, Inc.

Inventor： Michael Poslusney ,  Glen Ernst ,  James Barrow ,  Yifang Huang

IPC: C07D401/12 ,  C07D213/82 ,  C07D413/12 ,  C07D417/12 ,  A61K31/4439 ,  A61K31/444 ,  A61K31/51 ,  A61K31/44

Abstract: Pyridine carboxamide compounds for inhibiting NaV1.8 and methods for treating a condition, disease, or disorder associated with an increased NaV1.8 activity or expression are disclosed.

公开(公告)号：US11136322B2

公开(公告)日：2021-10-05

申请号：US16291403

申请日：2019-03-04

Applicant: THE JOHNS HOPKINS UNIVERSITY ,  LIEBER INSTITUTE, INC.

Inventor： Pankaj Pasricha ,  Yifang Huang ,  James Barrow

IPC: A61K31/5517 ,  A61P25/00 ,  C07D487/04 ,  C07D243/12 ,  A61K45/06 ,  A61K31/5513 ,  C07D243/24

Abstract: The present invention provides compounds and compositions which are positive allosteric modulators of GABA-A receptors that selectively target the peripheral nervous system and organs of the body, and which do not pass through the blood-brain barrier. The compounds and compositions of the present invention are useful for treatment of diseases or disorders which are mediated by GABA-A neuronal activity, such as, for example, visceral pain, gut motility, irritable bowel syndrome, functional abdominal pain, functional idiopathic diarrhea, inflammatory bowel diseases, drug induced pain, bile salt malabsorption, lactase or other carbohydrate intolerance.

公开(公告)号：US20210261542A1

公开(公告)日：2021-08-26

申请号：US17195149

申请日：2021-03-08

Applicant: The Johns Hopkins University ,  Lieber Institute, Inc.

Inventor： Marikki Laiho ,  Laureen Colis ,  James C. Barrow ,  Glen Ernst ,  Sara Sanders

IPC: C07D471/04 ,  A61K31/519 ,  A61K31/5377 ,  A61K45/06

Abstract: RNA polymerase I (Pol I) is a dedicated polymerase for the transcription of the 47S ribosomal RNA precursor subsequently processed into the mature 5.8S, 18S and 28S ribosomal RNAs and assembled into ribosomes in the nucleolus. Pol I activity is commonly deregulated in human cancers. Based on the discovery of lead molecule BMH-21, a series of pyridoquinazolinecarboxamides were synthesized as inhibitors of Pol I and activators of the destruction of RPA194, the Pol I large catalytic subunit protein. The present invention identifies a set of bioactive compounds, including purified stereoisomers, that potently cause RPA194 degradation that function in a tightly constrained chemical space. Pharmaceutical compositions comprising these compounds and their uses in cancer and other Pol I related diseases is also provided.

公开(公告)号：US20210139456A1

公开(公告)日：2021-05-13

申请号：US17256784

申请日：2019-07-09

Applicant: Lieber Institute, Inc.

Inventor： Michael Poslusney ,  Glen Ernst ,  James Barrow

IPC: C07D401/12 ,  C07D237/16

Abstract: Pyridazine compounds for inhibiting NaV1.8 and methods for treating a condition, disease, or disorder associated with an increased NaV1.8 activity or expression are disclosed.

公开(公告)号：US20200062759A1

公开(公告)日：2020-02-27

申请号：US16291403

申请日：2019-03-04

Applicant: THE JOHNS HOPKINS UNIVERSITY ,  LIEBER INSTITUTE, INC.

Inventor： Pankaj Pasricha ,  Yifang Huang ,  James Barrow

IPC: C07D487/04 ,  A61K31/5517 ,  C07D243/12 ,  A61K45/06 ,  A61K31/5513 ,  C07D243/24

Abstract: The present invention provides compounds and compositions which are positive allosteric modulators of GABA-A receptors that selectively target the peripheral nervous system and organs of the body, and which do not pass through the blood-brain barrier. The compounds and compositions of the present invention are useful for treatment of diseases or disorders which are mediated by GABA-A neuronal activity, such as, for example, visceral pain, gut motility, irritable bowel syndrome, functional abdominal pain, functional idiopathic diarrhea, inflammatory bowel diseases, drug induced pain, bile salt malabsorption, lactase or other carbohydrate intolerance.

公开(公告)号：US20170197967A1

公开(公告)日：2017-07-13

申请号：US15320866

申请日：2015-06-26

Applicant: THE JOHNS HOPKINS UNIVERSITY ,  LIEBER INSTITUTE, INC.

Inventor： Pankaj Pasricha ,  Yifang Huang ,  James Barrow

IPC: C07D487/04 ,  C07D243/24 ,  A61K31/5513 ,  A61K31/5517

CPC classification number: C07D487/04 ,  A61K31/5513 ,  A61K31/5517 ,  A61K45/06 ,  C07D243/12 ,  C07D243/24 ,  A61K2300/00

Abstract: The present invention provides compounds and compositions which are positive allosteric modulators of GABA-A receptors that selectively target the peripheral nervous system and organs of the body, and which do not pass through the blood-brain barrier. The compounds and compositions of the present invention are useful for treatment of diseases or disorders which are mediated by GABA-A neuronal activity, such as, for example, visceral pain, gut motility, irritable bowel syndrome, functional abdominal pain, functional idiopathic diarrhea, inflammatory bowel diseases, drug induced pain, bile salt malabsorption, lactase or other carbohydrate intolerance.