US2020385402A1PendingUtilityA1
Maytansinoid Derivatives, Conjugates Thereof, and Methods of Use
Est. expiryMar 27, 2035(~8.7 yrs left)· nominal 20-yr term from priority
Inventors:Thomas Nittoli
A61P 35/00A61K 47/6889A61K 47/68033C07D 498/18A61K 47/6849A61K 31/5365C07D 498/08A61K 47/6803
64
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Claims
Abstract
Provided herein are maytansinoid derivatives, conjugates thereof, and methods of treating or preventing proliferative diseases with the same.
Claims
exact text as granted — not AI-modified1 - 62 . (canceled)
63 . A compound of Formula (I):
or a pharmaceutically acceptable salt thereof,
wherein:
A is an optionally substituted heteroarylene or a substituted arylene;
L is a linker;
BA is a binding agent; and
k is an integer from 1 to 30.
64 . The compound of claim 63 , wherein
BA is an antibody or antigen binding fragment thereof; and k is an integer from 1-6.
65 . The compound of claim 64 , wherein
A is
R 1 , independently at each occurrence, is alkyl, alkenyl, alkynyl, alkoxy, aryl, alkaryl, arylalkyl, halo, haloalkyl, haloalkoxy, heteroaryl, heterocycloalkyl, hydroxyl, cyano, nitro,
or azido;
R A is alkyl or heteroalkyl;
n is an integer from 1 to 4; and
q is an integer from 0 to 5.
66 . The compound of claim 65 , wherein
A is:
R 1 is halo, haloalkyl, alkoxy, alkyl,
heterocycloalkyl, or
and
R A is alkyl.
67 . The compound of claim 66 , wherein A is:
is the bond linking A to the N atom, and
is the bond linking A to the carbonyl.
68 . The compound of claim 64 , wherein
L is
SP is a spacer;
is one or more bonds to the binding agent;
R AA1 is an amino acid side chain; and
R AA2 is an amino acid side chain.
69 . The compound of claim 68 , wherein R AA1 is
and R AA2 is
70 . The compound of claim 68 , wherein
SP is
is a bond to the antibody or antigen binding fragment thereof;
is a bond to a cysteine on the antibody or antigen binding fragment thereof;
b is an integer from 2 to 8;
R N is a hydrogen atom or alkyl; and
R M is alkyl.
71 . The compound of claim 64 , wherein
L is
wherein:
is a bond to the antibody or antigen binding fragment thereof; and
is a bond to a cysteine on the antibody or antigen binding fragment thereof.
72 . The compound of claim 64 , wherein the compound is
wherein t is an integer from 1 to 6;
Ab is an antibody or antigen binding fragment thereof; and
S is a bond to a cysteine on said antibody or antigen binding fragment thereof.
73 . The compound of claim 64 , wherein the antibody, or antigen binding fragment thereof, binds PSMA, MUC16, or PRLR.
74 . The compound of claim 64 , wherein the antibody is an antibody or antigen binding fragment thereof that binds a tumor associated antigen.
75 . The compound of claim 66 , wherein A is
is the bond linking A to the N atom, and
is the bond linking A to the carbonyl.
76 . The compound of claim 64 , wherein the compound is
wherein t is an integer from 1 to 6;
Ab is an antibody or antigen binding fragment thereof; and
S is a bond to a cysteine on said antibody or antigen binding fragment thereof.
77 . The compound of claim 64 , wherein the compound is
wherein t is an integer from 1 to 6;
Ab is an antibody or antigen binding fragment thereof; and
S is a bond to a cysteine on said antibody or antigen binding fragment thereof.
78 . The compound of claim 64 , wherein the compound is
wherein t is an integer from 1 to 6;
Ab is an antibody or antigen binding fragment thereof; and
S is a bond to a cysteine on said antibody or antigen binding fragment thereof.
79 . The compound of claim 64 , wherein the compound is
wherein t is an integer from 1 to 6;
Ab is an antibody or antigen binding fragment thereof; and
S is a bond to a cysteine on said antibody or antigen binding fragment thereof.
80 . The compound of claim 64 , wherein the compound is
wherein t is an integer from 1 to 6; and
Ab is an antibody or antigen binding fragment thereof.
81 . The compound of claim 65 , wherein
A is:
R 1 is halo, haloalkyl, alkoxy, alkyl,
heterocycloalkyl, or
and
R A is alkyl.
82 . The compound of claim 65 , wherein
A is:
R 1 is alkoxy; and
n is 1.
83 . The compound of claim 63 , wherein k is an integer from 1 to 10.
84 . The compound of claim 63 , wherein k is an integer from 1 to 8.
85 . The compound of claim 63 , wherein k is an integer from 1 to 6.
86 . The compound of claim 63 , wherein k is an integer from 1 to 4.
87 . The compound of claim 63 , wherein k is an integer from 1 to 3.
88 . An antibody-drug conjugate comprising an antibody or antigen-binding fragment thereof conjugated to a compound selected from the group consisting of:
89 . A pharmaceutical composition comprising the compound of claim 63 and a pharmaceutically acceptable diluent, excipient, or carrier.
90 . A pharmaceutical composition comprising the compound of claim 77 and a pharmaceutically acceptable diluent, excipient, or carrier.
91 . A method for killing tumor cells comprising contacting the tumor cells with a compound of claim 63 or a pharmaceutical composition of claim 89 .
92 . A method for treating cancer in a patient comprising administering to a patient having said cancer a compound of claim 63 or a pharmaceutical composition of claim 89 .
93 . A method for killing tumor cells comprising contacting the tumor cells with a compound of claim 77 or a pharmaceutical composition of claim 90 .
94 . A method for treating cancer in a patient having the cancer comprising administering a compound of claim 77 or a pharmaceutical composition of claim 90 .
95 . A compound of Formula II:
or a pharmaceutically acceptable salt thereof,
wherein A is a substituted arylene.
96 . A compound of Formula P1:
wherein A is a substituted arylene and RL is a reactive linker.
97 . A process for preparing a compound of Formula I:
or a pharmaceutically acceptable salt thereof,
wherein:
A is a substituted arylene;
L is a linker;
BA is a binding agent; and
k is an integer from 1 to 30
comprising contacting a compound of Formula P1
wherein A is a substituted arylene and RL is a reactive linker with a binding agent.Join the waitlist — get patent alerts
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