公开(公告)号：US11866430B2

公开(公告)日：2024-01-09

申请号：US17254914

申请日：2019-06-26

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Louis S. Chupak ,  Min Ding ,  Robert G. Gentles ,  Yazhong Huang ,  Scott W. Martin ,  Ivar M. Mcdonald ,  Stephen E. Mercer ,  Richard E. Olson ,  Upender Velaparthi ,  Michael Wichroski ,  Xiaofan Zheng

IPC: C07D471/04 ,  A61K31/4375 ,  A61P35/00

CPC classification number: C07D471/04 ,  A61K31/4375 ,  A61P35/00

Abstract: Disclosed are compounds of Formula (I): or a salt thereof, wherein: R1, R2, R3, and R4 are defined herein. Also disclosed are methods of using such compounds to inhibit the activity of one or both of diacylglycerol kinase alpha (DGK α) and diacylglycerol kinase zeta (DGKζ), and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.

公开(公告)号：US20210277004A1

公开(公告)日：2021-09-09

申请号：US17254914

申请日：2019-06-26

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Louis S. Chupak ,  Min Ding ,  Robert G. Gentles ,  Yazhong Huang ,  Scott W. Martin ,  Ivar M. Mcdonald ,  Stephen E. Mercer ,  Richard E. Olson ,  Upender Velaparthi ,  Michael Wichroski ,  Xiaofan Zheng

IPC: C07D471/04 ,  A61P35/00

Abstract: Disclosed are compounds of Formula (I): or a salt thereof, wherein: R1, R2, R3, and R4 are defined herein. Also disclosed are methods of using such compounds to inhibit the activity of one or both of diacylglycerol kinase alpha (DGK α) and diacylglycerol kinase zeta (DGKζ), and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.

公开(公告)号：US11058767B2

公开(公告)日：2021-07-13

申请号：US16282138

申请日：2019-02-21

Applicant: Bristol-Myers Squibb Company ,  Roche Innovation Center Copenhagen A/S

Inventor： Richard E. Olson ,  Brian R. Anderson ,  Peter Hagedorn ,  Marianne Lerbech Jensen ,  Ivar M. McDonald ,  Stephen E. Mercer

IPC: C07H21/02 ,  C07H21/04 ,  A61K39/395 ,  A61K47/54 ,  A61K47/64 ,  A61K47/60 ,  A61P9/12 ,  A61P9/04 ,  A61K9/00 ,  C12N5/074 ,  C12N5/077 ,  C12N15/113 ,  A61K31/713 ,  A61K39/00

Abstract: The present disclosure relates to antisense oligonucleotides, which target CAMK2D mRNA in a cell, leading to reduced expression of CAMK2D protein. Reduction of CAMK2D protein expression is beneficial for the treatment of certain medical disorders, e.g., cardiovascular-related diseases or disorders.

公开(公告)号：US09833454B2

公开(公告)日：2017-12-05

申请号：US15300602

申请日：2015-04-01

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Kenneth M. Boy ,  Stephen E. Mercer ,  Richard E. Olson ,  Xiaoliang Zhou

IPC: C07D239/70 ,  C07D491/00 ,  C07D471/00 ,  C07D413/00 ,  A61K31/517 ,  C07D403/12

CPC classification number: A61K31/517 ,  A61K2121/00 ,  C07D403/12

Abstract: The compound N2-(3-(difluoromethoxy)-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-7-(4-fluorophenyl)-N4,5,5-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine: [PLEASE INSERT CHEMICAL STRUCTURE HERE] reduces -amyloid peptide (A 42) production and has low potential for bioactivation, and may be useful in the treatment of Alzheimer's Disease and other conditions affected by -amyloid peptide (A 42) production.

公开(公告)号：US20190275148A1

公开(公告)日：2019-09-12

申请号：US16282138

申请日：2019-02-21

Applicant: Bristol-Myers Squibb Company ,  Roche Innovation Center Copenhagen A/S

Inventor： Richard E. Olson ,  Brian R. Anderson ,  Peter Hagedorn ,  Marianne Lerbech Jensen ,  Ivar M. McDonald ,  Stephen E. Mercer

IPC: A61K39/395 ,  C12N5/077 ,  C12N15/113 ,  C12N5/074 ,  A61K47/60 ,  A61K47/64 ,  A61K47/54 ,  A61P9/04 ,  A61P9/12 ,  A61K9/00

Abstract: The present disclosure relates to antisense oligonucleotides, which target CAMK2D mRNA in a cell, leading to reduced expression of CAMK2D protein. Reduction of CAMK2D protein expression is beneficial for the treatment of certain medical disorders, e.g., cardiovascular-related diseases or disorders.

公开(公告)号：US11761951B2

公开(公告)日：2023-09-19

申请号：US15548390

申请日：2016-02-04

Applicant: Bristol-Myers Squibb Company ,  Roche Innovation Center Copenhagen A/S

Inventor： Richard E. Olson ,  Angela M. Cacace ,  Peter Hagedorn ,  Anja Mølhart Høg ,  Niels Fisker Nielsen ,  Dong LI ,  Jeffrey M. Brown ,  Stephen E. Mercer ,  Marianne Lerbech Jensen

IPC: G01N33/50 ,  A61K49/00 ,  C12N15/113 ,  G01N33/53 ,  G01N33/68

CPC classification number: G01N33/5014 ,  A61K49/0008 ,  C12N15/113 ,  G01N33/5058 ,  G01N33/5308 ,  G01N33/68 ,  C12N2310/31 ,  C12N2310/311 ,  C12N2310/314 ,  C12N2310/3125 ,  C12N2310/3231 ,  C12N2310/341

Abstract: The present disclosure provides methods of using a calcium oscillation assay and/or a sequence score calculation to identify a molecule that is safe for administration. The disclosure also includes a method of selecting or identifying a molecule having tolerable in vivo neurotoxicity using a calcium oscillation assay, a sequence score method, an in vivo tolerability assay, or any combination thereof.

公开(公告)号：US20180161356A1

公开(公告)日：2018-06-14

申请号：US15549021

申请日：2016-02-04

Applicant: BRISTOL-MYERS SQUIBB COMPANY ,  ROCHE INNOVATION CENTER COPENHAGEN A/S

Inventor： Richard E. Olson ,  Angela M. Cacace ,  Peter Hagedorn ,  Anja Mølhart Høg ,  Marianne Lerbech Jensen ,  Niels Fisker Nielsen ,  Dong Li ,  Jeffrey M. Brown ,  Stephen E. Mercer

IPC: A61K31/712 ,  A61P25/28

CPC classification number: A61K31/712 ,  A61K2121/00 ,  A61P25/28 ,  C12N15/113 ,  C12N2310/11 ,  C12N2310/315 ,  C12N2310/3231 ,  C12N2310/341 ,  C12N2310/343 ,  C12N2310/346

Abstract: The present invention relates to oligomer compounds (oligomers), which target Tau mRNA in a cell, leading to reduced expression of Tau protein. Reduction of Tau protein expression is beneficial for the treatment of certain medical disorders, e.g., a neurological disorder.

公开(公告)号：US20170182050A1

公开(公告)日：2017-06-29

申请号：US15300602

申请日：2015-04-01

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Kenneth M. Boy ,  Stephen E. Mercer ,  Richard E. Olson ,  Xiaoliang Zhou

IPC: A61K31/517 ,  C07D403/12

CPC classification number: A61K31/517 ,  A61K2121/00 ,  C07D403/12

Abstract: The compound N2-(3-(difluoromethoxy)-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-7-(4-fluorophenyl)-N4,5,5-trimethyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine: [PLEASE INSERT CHEMICAL STRUCTURE HERE] reduces -amyloid peptide (A 42) production and has low potential for bioactivation, and may be useful in the treatment of Alzheimer's Disease and other conditions affected by -amyloid peptide (A 42) production.