IP Library › Granted Patent US 8,940,896
Granted Patent B2
US 8,940,896 · App. 10/592,761 · Granted Jan 27, 2015

Tetra-cyclic carboline derivatives useful in the inhibition of angiogenesis

View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 8,940,896
App. No.
10/592,761
Granted
Jan 27, 2015
Kind
B2
Abstract

In accordance with the present invention, tetracyclic caboline derivatives that inhibit the expression of VEGF post-transcriptionally have been identified, and methods for their use provided. In one aspect of the invention, these compounds useful in the inhibition of VEGF production, in the inhibition of angiogenesis, and/or in the treatment of cancer, diabetic retinopathy or exudative macular degeneration are provided. In another aspect of the invention, methods are provided for the inhibition of VEGF production, the inhibition of angiogenesis, and/or the treatment of cancer, diabetic retinopathy or exudative macular degeneration using the compounds of the invention.

Claims (55)

1. A compound having a structure selected from the group consisting of:

or a pharmaceutically acceptable salt, racemate or stereoisomer thereof.

2. A compound of Formula I,

or a pharmaceutically acceptable salt, racemate or stereoisomer of said compound; wherein

X is hydrogen, a hydroxyl, a halogen, methyl or methoxy;

R 1 is selected from the group consisting of:

wherein indicates a point of attachment; and

R 2 is selected from the group consisting of:

wherein and * each indicate a point of attachment,

wherein, when R 1 is

then R 2 is

wherein, when R 1 is

then R 2 is selected from the group consisting of:

and

wherein, when R 1 is

then R 2 is selected from the group consisting of:

3. The compound of claim 2 , wherein said compound is an 10S, 3aR isomer of a compound of Formula I.

4. The compound of claim 2 , wherein said compound is an 5S, 11aR isomer of a compound of Formula I.

5. The compound of claim 2 , wherein:

R 1 is selected from the group consisting of:

and

R 2 is selected from the group consisting of:

wherein, when R 1 is

then R 2 is

wherein, when R 1 is

then R 2 is selected from the group consisting of:

and

wherein, when R 1 is

then R 2 is selected from the group consisting of:

6. The compound of claim 2 , wherein R 1 is selected from the group consisting of:

wherein indicates a point of attachment, and

R 2 is selected from the group consisting of:

wherein * indicates a point of attachment,

wherein, when R 1 is

then R 2 is

and

wherein, when R 1 is

then R 2 is selected from the group consisting of:

7. The compound of claim 2 , wherein R 1 is:

wherein indicates a point of attachment, and

R 2 is selected from the group consisting of:

wherein * indicates a point of attachment.

8. The compound of claim 2 , wherein R 1 is selected from the group consisting of:

wherein indicates a point of attachment, and

R 2 is selected from the group consisting of:

wherein * indicates a point of attachment,

wherein, when R 1 is

then R 2 is

and;

wherein, when R 1 is

then R 2 is selected from the group consisting of:

9. The compound of claim 2 , wherein R 1 is selected from the group consisting of:

wherein indicates a point of attachment, and

R 2 is selected from the group consisting of:

wherein * indicates a point of attachment.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded Jul 14, 2020
From: MIDCAP FINANCIAL TRUST, AS AGENT
To: PTC THERAPEUTICS, INC.
Reel/Frame 053209/0872 →
CORRECTIVE ASSIGNMENT TO CORRECT THE INCLUSION OF 6420591,6583309,6503713, 5843995,7029846,7056656, 6468969,6486305,6630294, 6989256,6627398,8247167, 9017935 PREVIOUSLY RECORDED ON REEL 042418 FRAME 0774. ASSIGNOR(S) HEREBY CONFIRMS THE SECURITY INTEREST. Recorded Aug 24, 2017
From: PTC THERAPEUTICS, INC.
To: MIDCAP FINANCIAL TRUST, AS AGENT
Reel/Frame 043672/0096 →
SECURITY INTEREST Recorded May 8, 2017
From: PTC THERAPEUTICS, INC.
To: MIDCAP FINANCIAL TRUST, AS AGENT
Reel/Frame 042418/0774 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 25, 2007
From: MOON, YOUNG-CHOON; CAO, LIANGXIAN; TAMILARASU, NADARAJAN; QI, HONGYAN; CHOI, SOONGYU; LENNOX, WILLIAM JOSEPH; CORSON, DONALD THOMAS
To: PTC THERAPEUTICS, INC.
Reel/Frame 020016/0155 →