US 11,712,480 B2
Heteroaryl sulfone-based conjugation handles, methods for their preparation, and their use in synthesizing antibody drug conjugates
Russell George Dushin, Old Lyme, CT (US); Daniel P. Uccello, Colchester, CT (US); Jeremy Starr, Mystic, CT (US); Ye Che, Niantic, CT (US); Mark Flanagan, Gales Ferry, CT (US); Jeffrey M. Casavant, Franklin, CT (US); Christopher John O'Donnell, Mystic, CT (US); Gary Frederick Filzen, Schwenksville, PA (US); Jennifer Young, Groton, CT (US); Joseph A. Abramite, San Diego, CA (US); Lawrence N. Tumey, Pawcatuck, CT (US); Ludivine Moine, Uncasville, CT (US); Adam Matthew Gilbert, Guilford, CT (US); and Lee R. Roberts, Cambridge, MA (US)
Assigned to Pfizer Inc., New York, NY (US)
Appl. No. 16/321,695
Filed by PFIZER INC., New York, NY (US)
PCT Filed Jul. 31, 2017, PCT No. PCT/IB2017/054675
§ 371(c)(1), (2) Date Jan. 29, 2019,
PCT Pub. No. WO2018/025168, PCT Pub. Date Feb. 8, 2018.
Claims priority of provisional application 62/530,554, filed on Jul. 10, 2017.
Claims priority of provisional application 62/370,270, filed on Aug. 3, 2016.
Prior Publication US 2021/0308276 A1, Oct. 7, 2021
Int. Cl. A61K 47/54 (2017.01); A61K 47/68 (2017.01); C07K 4/00 (2006.01); C07K 5/02 (2006.01); C07K 7/02 (2006.01); A61K 47/50 (2017.01); C07K 5/062 (2006.01)
CPC A61K 47/6855 (2017.08) [A61K 47/50 (2017.08); A61K 47/545 (2017.08); A61K 47/6867 (2017.08); C07K 4/00 (2013.01); C07K 5/0205 (2013.01); C07K 5/06052 (2013.01); C07K 7/02 (2013.01)] 8 Claims
 
1. A compound of Formula (I):

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt or solvate thereof, wherein:
Het is a mono-, bi-, or polycyclic heteroaryl ring system having 1-4 heteroatoms,
wherein a carbon atom on said ring system bound to —S(O2)— is adjacent to at least one heteroatom on said ring system, and wherein each heteroatom is independently selected from the group consisting of N, O, and S;
m is 0, 1, 2, 3, 4, or 5;
n is 0, 1, 2, 3, 4, or 5;
p is 0, 1, or 2;
q is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10;
r is 0, 1, or 2;
s is 0, 1, or 2;
t is 0 or 1;
w is 1 or 2;
each E is independently selected from the group consisting of: —C(R1)2—, —O—C(R1)2—C(R1)2— where r is 2, and —C(R1)2—C(R1)2—O— where s is 1 or 2;
each R1 is independently selected from the group consisting of: H, C1-C6 straight or branched alkyl, C2-C6 straight or branched alkenyl, and C2-C6 straight or branched alkynyl;
R2 is C1-C10 alkyl optionally substituted with a halogen or haloalkyl, or C5-C12 aryl optionally substituted with a halogen or haloalkyl;
each X is an independently selected amino acid;
each Y is an independently selected amino acid;
each Z is an independently selected spacer element; and
D is dolastatin, MMAD, MMAE, MMAF, PF-06380101, an active agent, a moiety capable of binding to an active agent;
wherein
(a) D is selected from the group consisting of dolastatin, MMAD, MMAE, MMAF and PF-06380101; or
(b) Z is

OG Complex Work Unit Chemistry