MAYTANSINOID-BASED DRUG DELIVERY SYSTEMS

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 None
App. No.: 18/086,076

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present subject matter provides for albumin-binding prodrugs, maytansinoid-based compounds, and uses thereof.

Claims (70)

1 . A compound having the structure of Formula (I):

or a pharmaceutically acceptable salt, hydrate, solvate, or isomer thereof,

wherein:

R 1 is selected from —H and C 1 -C 4 alkyl;

Spacer is selected from:

V is absent or selected from —CH 2 —, —O— and —NR 3 —, wherein R 3 is —H or C 1 -C 4 alkyl; each R 2 is independently selected from —H, halogen (e.g., —F, —Cl, —Br or —I) and C 1 -C 4 alkyl or two R 2 s taken together form a C 3 -C 6 , cycloalkyl;

n is 0-3;

X is absent or selected from —CH 2 —, —O—, —S—, —Se—, and —NR 4 —, wherein R 4 is —H or C 1 -C 4 alkyl;

Y is selected from ═CH— and ═N—;

Z 1 , Z 2 , Z 3 and Z 4 are each independently selected from —H, halogen (e.g., —F, —Cl, —Br or —I), —CF 3 , —OCH 3 , —CN, —NO 2 , C 1 -C 4 alkyl and C 2 -C 4 alkoxy;

AA is an amino acid selected from glycine, D or L proline, sarcosine, N-ethyl-glycine, D or L alanine, D or L N-methylalanine, β-alanine, N-methyl-β-alanine, α-aminoisobutyric acid, and N-methyl-α-aminoisobutyric acid;

R′ is selected from O and

Y′ is absent or selected from an optionally substituted C 1 -C 6 alkyl, —NH—C(O)—, and —C(O)—NH—; or Y′ is selected from the group consisting of:

wherein n=0-6;

R 1′ is absent or selected from the group consisting of:

wherein M 1 is a pharmaceutically acceptable counter ion (e.g., H + , Na + , K + , Ca 2+ , Mg 2+ , NR 4 + , and NHR 3 + ; wherein R is H or C 1 -C 4 alkyl);

R 2′ is optionally substituted C 1 -C 18 alkyl wherein optionally up to six carbon atoms in said C 1 -C 18 alkyl are each independently replaced with —OCH 2 CH 2 —;

Z 1′ , Z 2′ , Z 3′ and Z 4′ are each independently selected from —H, halogen (e.g., —F, —Cl, —Br or —I), —CF 3 , —OCH 3 ,

—CN, —NO 2 , —SO 3 M 2 , and C 1 -C 4 alkyl wherein M 2 is a pharmaceutically acceptable counter ion (e.g., H + , Na + , K + , Ca 2+ , Mg 2+ , NR 4 + , and NHR 3 + ; wherein R is H or C 1 -C 4 alkyl);

TBG is a thiol-binding group selected from an optionally substituted maleimide group, an optionally substituted haloacetamide group, an optionally substituted haloacetate group, an optionally substituted pyridylthio group, an optionally substituted isothiocyanate group, an optionally substituted vinylcarbonyl group, an optionally substituted aziridine group, an optionally substituted disulfide group, an optionally substituted acetylene group, and an optionally substituted N-hydroxysuccininide ester group;

wherein said TBG is optionally bound to a thiol-bearing macromolecular carrier or thiol-bearing tumor-specific carrier.

2 .- 36 . (canceled)

37 . The compound of claim 1 , wherein said compound is selected from the group consisting of: