IP Library Granted Patent US 11,040,106
Granted Patent B2
US 11,040,106 · App. 16/407,264 · Granted Jun 22, 2021

Conjugates of kinase inhibitors and cyanine dyes

Inventors: Kevin Burgess (College Station, TX); Syed Muhammad Usama (College Station, TX)
Assignee: Small Molecule PPI Mimics LLC
A61K47/545A61K31/4545A61K31/506A61K31/519C09B23/0083
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Quick Facts
Patent No.
US 11,040,106
App. No.
16/407,264
Granted
Jun 22, 2021
Kind
B2
Abstract

The present disclosure provides conjugates of kinase inhibitors and cyanine dyes, as well as related compositions, methods and uses.

Claims (34)

1. A conjugate of Formula (Ia):

or a pharmaceutically acceptable salt thereof, wherein:

L is selected from optionally substituted C 1-10 alkyl, and optionally substituted heteroC 1-10 alkyl;

K is selected from:

each — is a covalent bond;

X is halogen;

Z is one or more anions to achieve electrical neutrality;

R2 and R3 combine to form a five- or six-membered ring, wherein the five- or six-membered ring is optionally substituted and optionally fused to an aryl or heteroaryl ring;

R4 and R5 independently are hydrogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, or optionally substituted heteroaryl;

R6 and R7 are independently hydrogen, or aliphatic, or combine to form a five- or six-membered carbocyclic or heterocyclic ring;

R8 and R9 independently are hydrogen, optionally substituted aliphatic, optionally substituted heteroaliphatic, optionally substituted aryl, or optionally substituted heteroaryl;

R10 and R11 combine to form a five- or six-membered ring, wherein the five- or six-membered ring is optionally substituted and optionally fused to an aryl or heteroaryl ring; and

R12 is optionally substituted aliphatic, or optionally substituted heteroaliphatic.

2. A method of inhibiting the proliferation of a cancer cell, comprising contacting the cell with a conjugate of claim 1 .

3. A method of treating cancer in a subject in need thereof, comprising administering a conjugate of claim 1 .

4. The conjugate of claim 1 , wherein Formula (Ia) is of Formula (Ib):

or a pharmaceutically acceptable salt thereof.

5. The conjugate of claim 4 , wherein Formula (Ib) is of Formula (Ic):

or a pharmaceutically acceptable salt thereof, wherein:

R13 and R14 independently are hydrogen, halogen, cyano, nitro, optionally substituted amino, optionally substituted alkyl, or optionally substituted heteroalkyl; and

Y is C(R15)(R16) or N(R17)(R18); wherein:

R15 and R16 independently are hydrogen, alkyl, heteroalkyl, aryl or heteroaryl; and

R17 and R18 independently are alkyl, heteroalkyl, aryl or heteroaryl.

6. The conjugate of claim 5 , wherein Formula (Ic) is of Formula (Id):

or a pharmaceutically acceptable salt thereof.

7. The conjugate of claim 5 , wherein Formula (Ic) is of Formula (Ie):

or a pharmaceutically acceptable salt thereof.

8. The conjugate of claim 7 , wherein Formula (Ie) is of Formula (If):

or a pharmaceutically acceptable salt thereof, wherein:

m and n independently are 2-20.

9. The conjugate of claim 1 , wherein X is chlorine.

10. The conjugate of claim 5 , wherein R13 and R14 are hydrogen; or wherein R13 and R14 are halogen.

11. The conjugate of claim 1 , having the structure selected of:

or a pharmaceutically acceptable salt thereof.

Assignments (1)
CONFIRMATORY LICENSE Recorded Apr 30, 2024
From: KEVIN BURGESS
To: UNITED STATES GOVERNMENT
Reel/Frame 067265/0138 →
Continuity (3)
Provisional Application 62721451 · Aug 22, 2018
Provisional Application 62669792 · May 10, 2018
Related Publication 20190343958A1 · Nov 14, 2019