US 11,911,483 B2
Modified self-immolating moieties for use in prodrugs and conjugates and methods of using and making
Yam B. Poudel, Fremont, CA (US); and Sanjeev Gangwar, Foster City, CA (US)
Assigned to Bristol-Myers Squibb Company, Princeton, NJ (US)
Filed by BRISTOL-MYERS SQUIBB COMPANY, Princeton, NJ (US)
Filed on Dec. 18, 2020, as Appl. No. 17/126,555.
Application 17/126,555 is a continuation of application No. 16/425,596, filed on May 29, 2019, granted, now 10,898,578.
Claims priority of provisional application 62/677,307, filed on May 29, 2018.
Prior Publication US 2021/0113706 A1, Apr. 22, 2021
This patent is subject to a terminal disclaimer.
Int. Cl. A61K 47/65 (2017.01); A61K 47/64 (2017.01); A61K 47/68 (2017.01); A61P 35/00 (2006.01); A61K 45/06 (2006.01)
CPC A61K 47/65 (2017.08) [A61K 45/06 (2013.01); A61K 47/6425 (2017.08); A61K 47/6865 (2017.08); A61P 35/00 (2018.01)] 6 Claims
 
1. A compound represented by formula (I)

OG Complex Work Unit Chemistry
wherein
R1 is C1-C5 alkyl, N3, OH, SH, ONH2, NH2, CO2H,

OG Complex Work Unit Chemistry
R2 is the side chain residue of an amino acid selected from the group consisting of alanine, β-alanine, γ-aminobutyric acid, arginine, asparagine, aspartic acid, γ-carboxyglutamic acid, citrulline, cysteine, glutamic acid, glutamine, glycine, histidine, isoleucine, leucine, lysine, methionine, norleucine, norvaline, ornithine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine;
n is 2 3, 4, or 5;

OG Complex Work Unit Chemistry
comprising a polypeptide whose bond to

OG Complex Work Unit Chemistry
is cleavable by cathepsin B;
R3 is NH,

OG Complex Work Unit Chemistry
R4 is

OG Complex Work Unit Chemistry
L is the residue of a bioactive molecule of the formula L-R3H; and
X is spacer group.