US 12,296,017 B2
Bioorthogonal compositions
Jose Manuel Mejia Oneto, San Francisco, CA (US); Nathan Yee, San Francisco, CA (US); Maksim Royzen, San Francisco, CA (US); Sangeetha Srinivasan, San Francisco, CA (US); and Ethan Miller, San Francisco, CA (US)
Assigned to Tambo, Inc., San Francisco, CA (US)
Filed by TAMBO, INC., San Francisco, CA (US); and THE RESEARCH FOUNDATION FOR THE STATE UNIVERSITY OF NEW YORK, Albany, NY (US)
Filed on Dec. 14, 2021, as Appl. No. 17/550,731.
Application 17/550,731 is a division of application No. 16/603,471, granted, now 11,253,600, previously published as PCT/US2018/026551, filed on Apr. 6, 2018.
Claims priority of provisional application 62/626,978, filed on Feb. 6, 2018.
Claims priority of provisional application 62/623,329, filed on Jan. 29, 2018.
Claims priority of provisional application 62/623,245, filed on Jan. 29, 2018.
Claims priority of provisional application 62/609,943, filed on Dec. 22, 2017.
Claims priority of provisional application 62/568,586, filed on Oct. 5, 2017.
Claims priority of provisional application 62/515,948, filed on Jun. 6, 2017.
Claims priority of provisional application 62/507,973, filed on May 18, 2017.
Claims priority of provisional application 62/483,163, filed on Apr. 7, 2017.
Claims priority of provisional application 62/483,121, filed on Apr. 7, 2017.
Claims priority of provisional application 62/483,081, filed on Apr. 7, 2017.
Prior Publication US 2022/0168426 A1, Jun. 2, 2022
Int. Cl. A61K 47/61 (2017.01); A61K 45/06 (2006.01); A61K 47/54 (2017.01); A61K 49/00 (2006.01); A61P 31/04 (2006.01); A61P 35/00 (2006.01)
CPC A61K 47/545 (2017.08) [A61K 45/06 (2013.01); A61K 47/542 (2017.08); A61K 47/61 (2017.08); A61K 49/0041 (2013.01); A61K 49/0043 (2013.01); A61K 49/0052 (2013.01); A61K 49/0054 (2013.01); A61P 31/04 (2018.01); A61P 35/00 (2018.01)] 14 Claims
 
1. A method of treating a cancer or bacterial infection comprising administering to a subject in need thereof, a therapeutically effective amount of a compound of formula (I-A), or a pharmaceutically acceptable salt thereof,

OG Complex Work Unit Chemistry
wherein
R1a is selected from the group consisting of C1-4alkyl, C1-4haloalkyl, and C1-4alkoxy;
R1b is selected from the group consisting of G1, OH, —NR1c—C1-4alkylene-G1, —NR1c—C1-4alkylene-N(R1d)2, —N(R1c)CHR1eCO2H, —N(R1c)—C1-6alkylene-CO2H, —N(R1f)—C2-4alkylene-(N(C1-4alkylene-CO2H)—C2-4alkylene)n-N(C1-4alkylene-CO2H)2, —N(R1c)CHR1eC(O)OC1-6alkyl, —N(R1c)—C1-6alkylene-C(O)OC1-6alkyl, and —N(R1f)—C2-4alkylene-(N(C1-4alkylene-C(O)OC1-6alkyl)-C2-4alkylene)n-N(C1-4alkylene-C(O)OC1-6alkyl)2;
R1c and R1d, at each occurrence, are independently hydrogen or C1-4alkyl;
R1e is —C1-4alkylene-CO2H, —C1-4alkylene-CONH2, or —C1-4alkylene-OH;
R1f is hydrogen, C1-6alkyl, or C1-4alkylene-CO2H;
D, at each occurrence, is independently a therapeutic agent selected from an anti-cancer agent and an antibiotic agent;
L1- is a linker;
L2- is selected from the group consisting of —C(O)— and C1-3alkylene;
G1 is an optionally substituted heterocyclyl;
m is 1, 2, or 3;
n is 0, 1, 2, or 3; and
p is 0, 1, or 2;
and administering a therapeutic support composition, the therapeutic support composition comprising a biocompatible support and a tetrazine-containing group of formula

OG Complex Work Unit Chemistry
wherein
R20 is selected from the group consisting of hydrogen, halogen, cyano, nitro, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, cycloalkenyl, CF3, CF2—R′, NO2, OR′, SR′, C(═O)R′, C(═S)R′, OC(═O)R′″, SC(═O)R″, OC(═S)R′″, SC(═S)R′″, S(═O)R′, S(═O)2R″, S(═O)2NR′R″, C(═O)O—R′, C(═O)S—R′, C(═S)O—R′, C(═S)S—R′, C(═O)NR′R″, C(═S)NR′R″, NR′R″, NR′C(═O)R″, NR′C(═S)R″, NR′C(═O)OR″, NR′C(═S)OR″, NR′C(═O) SR″, NR′C(═S) SR″, OC(═O)NR′R″, SC(═O)NR′R″, OC(═S)R′R′″, SC(═S)R′R″, NR′C(═O)NR″R″, and NR′C(═S)NR″R″;
R′ and R″ at each occurrence are independently selected from hydrogen, aryl and alkyl;
R″ at each occurrence is independently selected from aryl and alkyl;
R30 is halogen, cyano, nitro, hydroxy, alkyl, haloalkyl; alkenyl, alkynyl, alkoxy; halalkoxy; heteroalkyl, aryl, heteroaryl, heterocycle, cycloalkyl, or cycloalkenyl;
Ra, R31a and R31b are each independently hydrogen, C1-C6-alkyl, or C1-C6-haloalkyl; and
t is 0, 1, 2, 3, or 4.