公开(公告)号：US11028098B2

公开(公告)日：2021-06-08

申请号：US16151019

申请日：2018-10-03

Applicant: The Trustees of Columbia University in the City of New York

Inventor： Konstantin Petrukhin ,  Christopher Cioffi ,  Graham Johnson ,  Nicoleta Dobri ,  Emily Freeman ,  Ping Chen ,  Michael Conlon ,  Lei Zhu

IPC: C07D498/04 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  A61P27/02 ,  C07D401/06 ,  C07D405/14 ,  C07D409/06 ,  C07D491/052

Abstract: The present invention provide a compound having the structure: (structurally represented) wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl; R6 is H, OH, or halogen; B is a substituted or unsubstituted heterobicycle, pyridazine, pyrazole, pyrazine, thiadiazole, or triazole, wherein the heterocycle is other than chloro substituted indole; and the pyrazole, when substituted, is substituted with other than trifluoromethyl, or a pharmaceutically acceptable salt thereof.

公开(公告)号：US10421720B2

公开(公告)日：2019-09-24

申请号：US15935918

申请日：2018-03-26

Applicant: The Trustees of Columbia University in the City of New York

Inventor： Konstantin Petrukhin ,  Christopher Cioffi ,  Graham Johnson ,  Nicoleta Dobri ,  Emily Freeman ,  Ping Chen ,  Michael Conlon ,  Lei Zhu

IPC: A61K31/437 ,  A61K31/454 ,  C07D209/52 ,  C07D403/12 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04 ,  C07D209/02

Abstract: The present invention provides Octahydrocyclopentapyrrole compounds having the structure: (structurally represented) wherein psi is absent or present, and when present is a bond; R1, R2, R3, R4, and R5 are each independently H, halogen, CF, or C1-C4 alkyl; R6 is absent or present, and when present is H, OH, or halogen; A is absent or present, and when present is C(O) or C(O)NH; B is substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, benzyl, CO2H or (C1-C4 alkyl)-CO2H, wherein when B is CO2H, then A is present and is C(O); and when psi is present, then R6 is absent and when psi is absent, then R6 is present, or a pharmaceutically acceptable salt thereof, for treatment of diseases characterized by excessive lipofuscin accumulation in the retina.

公开(公告)号：US20210363155A1

公开(公告)日：2021-11-25

申请号：US17320158

申请日：2021-05-13

Applicant: The Trustees of Columbia University in the City of New York

Inventor： Konstantin Petrukhin ,  Christopher Cioffi ,  Graham Johnson ,  Nicoleta Dobri ,  Emily Freeman ,  Ping Chen ,  Michael Conlon ,  Lei Zhu

IPC: C07D498/04 ,  C07D471/04 ,  C07D487/04 ,  C07D495/04 ,  A61P27/02 ,  A61K31/501 ,  A61K31/437 ,  A61K31/4545 ,  A61K31/5025 ,  A61K31/506 ,  A61K31/4375 ,  A61K31/454 ,  A61K31/497 ,  C07D401/06 ,  C07D405/14 ,  C07D409/06 ,  C07D491/052

Abstract: The present invention provides a compound having the structure: wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl; R4 is H, OH, or halogen; B is a substituted or unsubstituted heterobicycle, pyridazine, pyrazole, pyrazine, thiadiazole, or triazole, wherein the heterobicycle is other than chloro substituted indole; and the pyrazole, when substituted, is substituted with other than trifluoromethyl, or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20210214360A1

公开(公告)日：2021-07-15

申请号：US17099231

申请日：2020-11-16

Applicant: The Trustees of Columbia University in the City of New York

Inventor： Konstantin Petrukhin ,  Christopher Cioffi ,  Graham Johnson ,  Rando Allikmets ,  Emily Freeman ,  Ping Chen ,  Michael Conlon ,  Lei Zhu

IPC: C07D487/04 ,  C07D471/04

Abstract: The present invention provides a compound having the structure: wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl, wherein two or more of R1, R2, R3, R4, or R5 are other than H; R6 is H, OH, or halogen; and B is a substituted or unsubstituted heterobicycle, wherein when R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is H, R2 is CF3, R3 is H, R4 is CF3, and R5 is H, or R1 is Cl, R2 is H, R3 is H, R4 is F, and R5 is H, or R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is CF3, R2 is F, R3 is H, R4 is H, and R5 is H, or R1 is Cl, R2 is F, R3 is H, R4 is H, and R5 is H, then B is other than or a pharmaceutically acceptable salt thereof.

公开(公告)号：US10570148B2

公开(公告)日：2020-02-25

申请号：US15944334

申请日：2018-04-03

Applicant: The Trustees of Columbia University In the City of New York

Inventor： Konstantin Petrukhin ,  Christopher Cioffi ,  Graham Johnson ,  Nicoleta Dobri ,  Emily Freeman ,  Ping Chen ,  Michael Conlon ,  Lei Zhu

IPC: C07D498/04 ,  C07D213/80 ,  C07D231/56 ,  C07D237/24 ,  C07D239/28 ,  C07D249/04 ,  C07D471/04 ,  C07D487/04 ,  C07D491/052 ,  C07C233/56 ,  C07D213/79

Abstract: The present invention provides a compound having the structure: (structurally represented) wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl; R6 is alkyl; A is absent or present, and when present is —C(O)— or —C(O)NH—; B is substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, benzyl, CO2H or (C1-C4 alkyl)-CO2H, wherein when B is CO2H, then A is present and is —C(O)—, or a pharmaceutically acceptable salt thereof.

公开(公告)号：US09926271B2

公开(公告)日：2018-03-27

申请号：US15457821

申请日：2017-03-13

Applicant: The Trustees of Columbia University in the City of New York

Inventor： Konstantin Petrukhin ,  Christopher Cioffi ,  Graham Johnson ,  Nicoleta Dobri ,  Emily Freeman ,  Ping Chen ,  Michael Conlon ,  Lei Zhu

IPC: C07D209/52 ,  C07D403/06 ,  C07D471/04 ,  C07D498/04 ,  C07D487/04 ,  C07D401/12 ,  C07D403/04 ,  C07D403/12 ,  C07D401/04

CPC classification number: C07D209/52 ,  A61K31/454 ,  C07D209/02 ,  C07D401/04 ,  C07D401/06 ,  C07D401/12 ,  C07D403/04 ,  C07D403/06 ,  C07D403/12 ,  C07D471/04 ,  C07D487/04 ,  C07D498/04

Abstract: The present invention provides Octahydrocyclopentapyrrole compounds having the structure: (structurally represented) wherein psi is absent or present, and when present is a bond; R1, R2, R3, R4, and R5 are each independently H, halogen, CF, or C1-C4 alkyl; R6 is absent or present, and when present is H, OH, or halogen; A is absent or present, and when present is C(O) or C(O)NH; B is substituted or unsubstituted monocycle, bicycle, heteromonocycle, heterobicycle, benzyl, CO2H or (C1-C4 alkyl)-CO2H, wherein when B is CO2H, then A is present and is C(O); and when psi is present, then R6 is absent and when psi is absent, then R6 is present, or a pharmaceutically acceptable salt thereof, for treatment of diseases characterized by excessive lipofuscin accumulation in the retina.

公开(公告)号：US11919913B2

公开(公告)日：2024-03-05

申请号：US17320158

申请日：2021-05-13

Applicant: The Trustees of Columbia University in the City of New York

Inventor： Konstantin Petrukhin ,  Christopher Cioffi ,  Graham Johnson ,  Nicoleta Dobri ,  Emily Freeman ,  Ping Chen ,  Michael Conlon ,  Lei Zhu

IPC: C07D498/04 ,  A61K31/437 ,  A61K31/4375 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/497 ,  A61K31/501 ,  A61K31/5025 ,  A61K31/506 ,  A61P27/02 ,  C07D401/06 ,  C07D405/14 ,  C07D409/06 ,  C07D471/04 ,  C07D487/04 ,  C07D491/052 ,  C07D495/04

CPC classification number: C07D498/04 ,  A61K31/437 ,  A61K31/4375 ,  A61K31/454 ,  A61K31/4545 ,  A61K31/497 ,  A61K31/501 ,  A61K31/5025 ,  A61K31/506 ,  A61P27/02 ,  C07D401/06 ,  C07D405/14 ,  C07D409/06 ,  C07D471/04 ,  C07D487/04 ,  C07D491/052 ,  C07D495/04

Abstract: The present invention provides a compound having the structure:






wherein
R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl;
R4 is H, OH, or halogen;
B is a substituted or unsubstituted heterobicycle, pyridazine, pyrazole, pyrazine, thiadiazole, or triazole,

wherein the heterobicycle is other than chloro substituted indole; and
the pyrazole, when substituted, is substituted with other than trifluoromethyl,

or a pharmaceutically acceptable salt thereof.

公开(公告)号：US20190031681A1

公开(公告)日：2019-01-31

申请号：US16151019

申请日：2018-10-03

Applicant: The Trustees of Columbia University in the City of New York

Inventor： Konstantin Petrukhin ,  Christopher Cioffi ,  Graham Johnson ,  Nicoleta Dobri ,  Emily Freeman ,  Ping Chen ,  Michael Conlon ,  Lei Zhu

IPC: C07D498/04 ,  C07D471/04 ,  C07D491/052 ,  C07D409/06 ,  C07D405/14 ,  C07D401/06 ,  C07D487/04 ,  C07D495/04

Abstract: The present invention provide a compound having the structure: (structurally represented) wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl; R6 is H, OH, or halogen; B is a substituted or unsubstituted heterobicycle, pyridazine, pyrazole, pyrazine, thiadiazole, or triazole, wherein the heterocycle is other than chloro substituted indole; and the pyrazole, when substituted, is substituted with other than trifluoromethyl, or a pharmaceutically acceptable salt thereof.

公开(公告)号：US11649240B2

公开(公告)日：2023-05-16

申请号：US17099231

申请日：2020-11-16

Applicant: The Trustees of Columbia University in the City of New York

Inventor： Konstantin Petrukhin ,  Christopher Cioffi ,  Graham Johnson ,  Rando Allikmets ,  Emily Freeman ,  Ping Chen ,  Michael Conlon ,  Lei Zhu

IPC: C07D471/04 ,  C07D487/04

CPC classification number: C07D487/04 ,  C07D471/04

Abstract: The present invention provides a compound having the structure:






wherein
R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl,

wherein two or more of R1, R2, R3, R4, or R5 are other than H;


R6 is H, OH, or halogen; and
B is a substituted or unsubstituted heterobicycle,
wherein when R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is H, R2 is CF3, R3 is H, R4 is CF3, and R5 is H, or R1 is Cl, R2 is H, R3 is H, R4 is F, and R5 is H, or R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is CF3, R2 is F, R3 is H, R4 is H, and R5 is H, or R1 is Cl, R2 is F, R3 is H, R4 is H, and R5 is H, then B is other than








or a pharmaceutically acceptable salt thereof.

公开(公告)号：US10407433B2

公开(公告)日：2019-09-10

申请号：US16058299

申请日：2018-08-08

Applicant: The Trustees of Columbia University in the City of New York

Inventor： Konstantin Petrukhin ,  Christopher Cioffi ,  Graham Johnson ,  Rando Allikmets ,  Emily Freeman ,  Ping Chen ,  Michael Conlon ,  Lei Zhu

IPC: A61K31/437 ,  C07D401/14 ,  C07D211/06 ,  C07D295/00 ,  C07D487/04 ,  C07D471/04

Abstract: The present invention provides a compound having the structure: wherein R1, R2, R3, R4, and R5 are each independently H, halogen, CF3 or C1-C4 alkyl, wherein two or more of R1, R2, R3, R4, or R5 are other than H; R6 is H, OH, or halogen; and B is a substituted or unsubstituted heterobicycle, wherein when R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is H, R2 is CF3, R3 is H, R4 is CF3, and R5 is H, or R1 is Cl, R2 is H, R3 is H, R4 is F, and R5 is H, or R1 is CF3, R2 is H, R3 is F, R4 is H, and R5 is H, or R1 is CF3, R2 is F, R3 is H, R4 is H, and R5 is H, or R1 is Cl, R2 is F, R3 is H, R4 is H, and R5 is H, then B is other than or a pharmaceutically acceptable salt thereof.