US 12,285,491 B2
Conjugation linkers, cell binding molecule-drug conjugates containing the linkers, methods of making and uses such conjugates with the linkers
Yongxin Robert Zhao, Hangzhou (CN); Qingliang Yang, Hangzhou (CN); Yuanyuan Huang, Hangzhou (CN); Shun Gai, Hangzhou (CN); Hangbo Ye, Hangzhou (CN); Linyao Zhao, Hangzhou (CN); Chengyu Yang, Hangzhou (CN); Huihui Guo, Hangzhou (CN); Xiaomai Zhou, Hangzhou (CN); Hongsheng Xie, Hangzhou (CN); Haifeng Zhu, Hangzhou (CN); Yifang Xu, Hangzhou (CN); Qianqian Tong, Hangzhou (CN); Junxiang Jia, Hangzhou (CN); Minjun Cao, Hangzhou (CN); Wenjun Li, Hangzhou (CN); Shuihong Gao, Hangzhou (CN); Zhixiang Guo, Hangzhou (CN); Lu Bai, Hangzhou (CN); Chen Li, Hangzhou (CN); Yanlei Yang, Hangzhou (CN); Chunyan Wang, Hangzhou (CN); and Zhichang Ye, Hangzhou (CN)
Assigned to HANGZHOU DAC BIOTECH CO., LTD., Hangzhou (CN)
Filed by Hangzhou DAC Biotech Co., Ltd., Hangzhou (CN)
Filed on Jun. 8, 2022, as Appl. No. 17/835,081.
Application 17/835,081 is a division of application No. 16/348,749, previously published as PCT/CN2016/105799, filed on Nov. 14, 2016.
Prior Publication US 2022/0313836 A1, Oct. 6, 2022
Int. Cl. A61K 47/68 (2017.01)
CPC A61K 47/6803 (2017.08) [A61K 47/68031 (2023.08); A61K 47/68035 (2023.08); A61K 47/6829 (2017.08); A61K 47/6831 (2017.08); A61K 47/6855 (2017.08); A61K 47/6863 (2017.08); A61K 47/6883 (2017.08); A61K 47/6889 (2017.08)] 11 Claims
OG exemplary drawing
 
1. A compound of Formula (XVII) or (XVIII):

OG Complex Work Unit Chemistry
wherein
custom character represent a single bond, and “custom character” can be an enantiomer or stereoisomer bond when linked to a single or a double bond;
custom character represents either a single bond, or a double bond, or a triple bond;
provided that when custom character represents a single bond, both Lv1 and Lv2 are not H; when custom character represents a double bond, either Lv1 or Lv2 can be H, but they are not H at the same time; when custom character represents a triple bond, Lv1 is absent and Lv2 can optionally be H;
Lv1 and Lv2 represent H or same or different leaving group that is optionally substituted by a thiol, and the leaving group is selected from the group consisting of a halide (selected from, fluoride, chloride, bromide, and iodide), methanesulfonyl (mesyl), toluenesulfonyl (tosyl), trifluoromethyl-sulfonyl (triflate), trifluoromethylsulfonate, nitrophenoxyl, N-succinimidyloxyl (NHS), phenoxyl; dinitrophenoxyl; pentafluorophenoxyl, tetrafluorophenoxyl, trifluorophenoxyl, difluorophenoxyl, monofluorophenoxyl, pentachlorophenoxyl, 1H-imidazole-1-yl, chlorophenoxyl, dichlorophenoxyl, trichlorophenoxyl, tetrachlorophenoxyl, N-(benzotriazol-yl) oxyl, 2-ethyl-5-phenylisoxazolium-3′-sulfonyl, phenyloxadiazole-sulfonyl (-sulfone-ODA), 2-ethyl-5-phenylisoxazoliumyl, phenyloxadiazolyl (ODA), or oxadiazolyl
R1 is a combination of two or more of C1-C8 alkyl; C2-C8 amide and polyethyleneoxy unit of formula (OCH2CH2)p or (OCH2CH(CH3))p, wherein p is an integer from 1 to about 1000;
T is

OG Complex Work Unit Chemistry
wherein custom character is the site of linkage,
m1, m2, m3, m4 and m5 are independently an integer from 1 to 10,
L1, L2, and X1, are absent; and
Drug is a selected from the group consisting of tubulysins, calicheamicins, auristatins, maytansinoids, CC-1065 compounds, daunorubicins, doxorubicins, taxanoids (taxanes), cryptophycins, epothilones, benzodiazepine dimers, calicheamicins and enediyne antibiotics, actinomycins, amanitins, azaserines, bleomycins, epirubicins, tamoxifen, idarubicin, dolastatins, auristatins, duocarmycins, geldanamycins, methotrexates, thiotepa, vindesines, vincristines, hemiasterlins, nazumamides, microginins, radiosumins, alterobactins, microsclerodermins, theonellamides, esperam1cms, siRNA, miRNA, piRNA, nucleolytic enzymes, and pharmaceutically acceptable salts and acids of any of the above molecules.