公开(公告)号：US20220213026A1

公开(公告)日：2022-07-07

申请号：US17431091

申请日：2020-02-14

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Dean A. Wacker ,  Susheel Jethanand Nara ,  Srinivas Cheruku ,  Kandhasamy Sarkunam ,  Firoz Ali Jaipuri ,  Soodamani Thangavel ,  Rishikesh Narayan ,  Subba Reddy Bandreddy ,  Srinivas Jogi ,  Pavan Kalyan Kathi

IPC: C07C233/61 ,  C07D295/04 ,  C07D207/06 ,  C07D205/04 ,  C07D309/04 ,  C07D405/14 ,  C07D271/06 ,  C07D277/64 ,  C07D413/04 ,  C07D405/04

Abstract: Disclosed are compounds of Formula (I) or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, wherein Q is a 5-membered heterocyclyl or 5-membered heteroaryl having 1 to 4 heteroatoms independently selected from N, O, and S, substituted with zero to 4 R1; and A, X1, X2, X3, X4, Z1, Z2, R1, R2, R3a, R3b, a, b, and d are defined herein. Also disclosed are methods of using these compounds to modulate the activity of farnesoid X receptor (FXR); pharmaceutical compositions comprising these compounds; and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

公开(公告)号：US12227496B2

公开(公告)日：2025-02-18

申请号：US17431006

申请日：2020-02-14

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Dean A. Wacker ,  Susheel Jethanand Nara ,  Srinivas Cheruku ,  Kandhasamy Sarkunam ,  Firoz Ali Jaipuri ,  Rishikesh Narayan ,  Subba Reddy Bandreddy ,  Srinivas Jogi

IPC: C07D413/12 ,  C07D217/06 ,  C07D271/06 ,  C07D403/12 ,  C07D413/14 ,  C07D417/12 ,  C07D417/14

Abstract: Disclosed are compounds of Formula (I): or a stereoisomer, a tautomer, or a salt or solvate thereof, wherein Q is C2-6 alkenyl or C2-6 alkynyl, each substituted with zero to 2 R1; and the other variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. Also disclosed are pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

公开(公告)号：US20220081430A1

公开(公告)日：2022-03-17

申请号：US17430903

申请日：2020-02-14

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Dean A. Wacker ,  Susheel Jethanand Nara ,  Srinivas Cheruku ,  Kandhasamy Sarkunam ,  Firoz Ali Jaipuri ,  Soodamani Thangavel ,  Rishikesh Narayan ,  Srinivas Jogi ,  Pavan Kalyan Kathi

IPC: C07D413/12 ,  C07D401/12 ,  C07D271/06 ,  C07D213/26 ,  C07D417/12

Abstract: Disclosed are compounds of Formula (I): or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, when Q is: (i) halo, cyano, hydroxyl, NRxRx, C(O)OH, C(O)NH2, C1-6 alkyl substiuted with zero to 6 R1a, or P(O)R1cR1c, or (ii) L R1; and A, X1, X2, X3, X4, Z1, Z2, R1, R1a, R1c, R2, R3a, R3b, Rx, L, a, b, and d are defined herein. Also disclosed are methods of using these compounds to modulate the activity of farnesoid X receptor (FXR); pharmaceutical compositions comprising these compounds; and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

公开(公告)号：US11254663B2

公开(公告)日：2022-02-22

申请号：US16789551

申请日：2020-02-13

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Dean A. Wacker ,  Susheel Jethanand Nara ,  Srinivas Cheruku ,  Kandhasamy Sarkunam ,  Firoz Ali Jaipuri ,  Soodamani Thangavel ,  Srinivas Jogi ,  Pavan Kalyan Kathi

IPC: C07D413/12 ,  C07D271/06 ,  A61P11/00

Abstract: Disclosed are compounds of Formula (I): or a stereoisomer, a tautomer, or a salt or solvate thereof, wherein all the variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. Also disclosed are pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

公开(公告)号：US20210261535A1

公开(公告)日：2021-08-26

申请号：US16789551

申请日：2020-02-13

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Dean A. Wacker ,  Susheel Jethanand Nara ,  Srinivas Cheruku ,  Kandhasamy Sarkunam ,  Firoz Ali Jaipuri ,  Soodamani Thangavel ,  Rishikesh Narayan ,  Subba Reddy Bandreddy ,  Srinivas Jogi ,  Pavan Kalyan Kathi

IPC: C07D413/12 ,  C07D271/06 ,  A61P11/00

Abstract: Disclosed are compounds of Formula (I): or a stereoisomer, a tautomer, or a salt or solvate thereof, wherein all the variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. Also disclosed are pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

公开(公告)号：US09174965B2

公开(公告)日：2015-11-03

申请号：US14400758

申请日：2013-05-13

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Matthias Broekema ,  Gang Wu ,  Dean A. Wacker

IPC: C07D401/14 ,  A61K31/506 ,  A61K31/403

CPC classification number: C07D401/14 ,  A61K31/403 ,  A61K31/506

Abstract: Novel compounds of structure Formula I: (I) or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein R1, R2 and R3 are defined herein, are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.

Abstract translation: 提供结构式I的新型化合物：其中R1，R2和R3在本文中定义的是GPR119G蛋白偶联受体调节剂，其中R 1，R 2和R 3在本文中定义，所述化合物是式（I）或其对映异构体，非对映异构体或其药学上可接受的盐。 GPR119 G蛋白偶联受体调节剂可用于治疗，预防或减缓需要GPR119 G蛋白偶联受体调节剂治疗的疾病进展。 因此，本公开还涉及包含这些新化合物的组合物以及通过使用任何这些新化合物或包含任何这些新化合物的组合物来治疗与GPR119G蛋白偶联受体的活性有关的疾病或病症的方法。

公开(公告)号：US12030835B2

公开(公告)日：2024-07-09

申请号：US17431091

申请日：2020-02-14

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Dean A. Wacker ,  Susheel Jethanand Nara ,  Srinivas Cheruku ,  Kandhasamy Sarkunam ,  Firoz Ali Jaipuri ,  Soodamani Thangavel ,  Rishikesh Narayan ,  Subba Reddy Bandreddy ,  Srinivas Jogi ,  Pavan Kalyan Kathi

IPC: C07C233/61 ,  C07D205/04 ,  C07D207/06 ,  C07D271/06 ,  C07D277/64 ,  C07D295/04 ,  C07D309/04 ,  C07D405/04 ,  C07D405/14 ,  C07D413/04

CPC classification number: C07C233/61 ,  C07D205/04 ,  C07D207/06 ,  C07D271/06 ,  C07D277/64 ,  C07D295/04 ,  C07D309/04 ,  C07D405/04 ,  C07D405/14 ,  C07D413/04

Abstract: Disclosed are compounds of Formula (I) or a stereoisomer, a tautomer, or a pharmaceutically acceptable salt or solvate thereof, wherein Q is a 5-membered heterocyclyl or 5-membered heteroaryl having 1 to 4 heteroatoms independently selected from N, O, and S, substituted with zero to 4 R1; and A, X1, X2, X3, X4, Z1, Z2, R1, R2, R3a, R3b, a, b, and d are defined herein. Also disclosed are methods of using these compounds to modulate the activity of farnesoid X receptor (FXR); pharmaceutical compositions comprising these compounds; and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

公开(公告)号：US20220162201A1

公开(公告)日：2022-05-26

申请号：US17431006

申请日：2020-02-14

Applicant: BRISTOL-MYERS SQUIBB COMPANY

Inventor： Dean A. Wacker ,  Susheel Jethanand Nara ,  Srinivas Cheruku ,  Kandhasamy Sarkunam ,  Firoz Ali Jaipuri ,  Rishikesh Narayan ,  Subba Reddy Bandreddy ,  Srinivas Jogi

IPC: C07D413/12 ,  C07D413/14 ,  C07D417/12 ,  C07D403/12 ,  C07D217/06 ,  C07D271/06 ,  C07D417/14

Abstract: Disclosed are compounds of Formula (I): or a stereoisomer, a tautomer, or a salt or solvate thereof, wherein Q is C2-6 alkenyl or C2-6 alkynyl, each substituted with zero to 2 R1; and the other variables are as defined herein. These compounds modulate the activity of farnesoid X receptor (FXR), for example, as agonists. Also disclosed are pharmaceutical compositions comprising these compounds and methods of treating a disease, disorder, or condition associated with FXR dysregulation, such as pathological fibrosis, transplant rejection, cancer, osteoporosis, and inflammatory disorders, by using the compounds and pharmaceutical compositions.

公开(公告)号：US08513265B2

公开(公告)日：2013-08-20

申请号：US13648436

申请日：2012-10-10

Applicant: Bristol-Myers Squibb Company

Inventor： John M. Fevig ,  Dean A. Wacker

IPC: C07D413/04 ,  A61K31/538

CPC classification number: C07D413/04 ,  C07D413/14 ,  C07D471/04 ,  C07D498/04

Abstract: Novel compounds are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. These novel compounds have the structure: or stereoisomers or prodrugs or pharmaceutically acceptable salts thereof, wherein n1, n2, n3, n4, A, B, D, E, G, Y, Z, R1 and R2 are defined herein.

Abstract translation: 提供了新的化合物，它们是GPR119G蛋白偶联受体调节剂。 GPR119 G蛋白偶联受体调节剂可用于治疗，预防或减缓需要GPR119 G蛋白偶联受体调节剂治疗的疾病进展。 这些新化合物具有以下结构：或其立体异构体或前药或其药学上可接受的盐，其中n1，n2，n3，n4，A，B，D，E，G，Y，Z，R1和R2如本文所定义。

公开(公告)号：US20130131074A1

公开(公告)日：2013-05-23

申请号：US13744604

申请日：2013-01-18

Applicant: Bristol-Myers Squibb Company

Inventor： Dean A. Wacker ,  Karen A. Rossi ,  Ying Wang ,  Gang Wu

IPC: C07D403/14 ,  A61K31/4545 ,  A61K45/06 ,  C07D403/12 ,  A61K31/501 ,  C07D401/12 ,  A61K31/506

CPC classification number: C07D403/14 ,  A61K31/4545 ,  A61K31/501 ,  A61K31/506 ,  A61K45/06 ,  C07D401/12 ,  C07D401/14 ,  C07D403/12 ,  C07D413/14

Abstract: Novel compounds of structure Formula I: or an enantiomer, a diastereomer, or a pharmaceutically acceptable salt thereof, wherein Z, R1, R2, R21, T1, T2, T3 and T4 are defined herein, are provided which are GPR119 G protein-coupled receptor modulators. GPR119 G protein-coupled receptor modulators are useful in treating, preventing, or slowing the progression of diseases requiring GPR119 G protein-coupled receptor modulator therapy. Thus, the disclosure also concerns compositions comprising these novel compounds and methods of treating diseases or conditions related to the activity of the GPR119 G protein-coupled receptor by using any of these novel compounds or a composition comprising any of such novel compounds.

Abstract translation: 提供结构式I的新型化合物或其对映体，非对映异构体或其药学上可接受的盐，其中Z，R 1，R 2，R 21，T 1，T 2，T 3和T 4在本文中定义，其是GPR119G蛋白偶联 受体调节剂。 GPR119 G蛋白偶联受体调节剂可用于治疗，预防或减缓需要GPR119 G蛋白偶联受体调节剂治疗的疾病进展。 因此，本公开还涉及包含这些新化合物的组合物以及通过使用任何这些新化合物或包含任何这些新化合物的组合物来治疗与GPR119G蛋白偶联受体的活性有关的疾病或病症的方法。