CD73 inhibitors
Inventors
Du, Xiaohui • Eksterowicz, John • Fantin, Valeria R. • Sun, Daqing • YE, Qiuping • Moore, Jared • Zavorotinskaya, Tatiana • BLANK, Brian R. • Rew, Yosup • Wu, Kejia • Zhu, Liusheng • Pham, Johnny • Kawai, Hiroyuki
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11807658-B2
Publication Date
2023-11-07
Expiration Date
Abstract
Described herein are CD73 inhibitors and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for the treatment of cancer, infections, and neurodegenerative diseases.
Core Innovation
The invention relates to treating cancer in a subject by administering a compound of Formula (IV), or a pharmaceutically acceptable salt thereof. The compounds of Formula (IV) are defined by Ring A, Q2, Q3, Q4, W, A, X, and multiple substituent variables with broad but specified structural ranges, including options for heteroatom assignments, optional substitution, and optional formation of a heterocycloalkyl from R1 and R2.
Ring A is defined by Q2 being N or CW, and Q3 and Q4 being N and CW in specified combinations. Each W is independently hydrogen, halogen, —CN, —ORb, NRcRd, C1-C6 alkyl, or C1-C6 haloalkyl, A is —O— or —CH2—, and X is —O—, —S—, —S(=O)2—, —NR17—, or —C(R18)2—. The substituent definitions further allow broad classes for R1 through R22, including alkyl, haloalkyl, alkenyl, alkynyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, sulfonyl, sulfonamide, carbonyl, and phosphonic-acid-related functional groups.
The cancer is selected from lung cancer, melanoma, breast cancer, ovarian cancer, colorectal cancer, gastric cancer, gallbladder cancer, prostate cancer, renal cancer, multiple myeloma, and lymphoma. The disclosure also states that the compounds are described in connection with methods of inhibiting CD73, CD73 biology, and the CD73→adenosine axis, with therapeutic context including cancer, infections, and neurodegenerative diseases.
Claims Coverage
One independent claim is identified. It covers a method of treating cancer by administering a compound of Formula (IV), or a pharmaceutically acceptable salt thereof, and includes multiple inventive feature groups defined by the Formula (IV) structural variables and by the cancer-selection limitation.
Treating cancer by administering a formula (iv) compound
A method of treating cancer in a subject comprising administering to the subject a compound of Formula (IV), or a pharmaceutically acceptable salt thereof.
Ring a and w definition
Ring A is defined by Q2 being N or CW and Q3/Q4 being N or CW in the specified combinations; each W is independently hydrogen, halogen, —CN, —ORb, NRcRd, C1-C6 alkyl, or C1-C6 haloalkyl.
Linker and heteroatom group selection
A is —O— or —CH2—, and X is —O—, —S—, —S(=O)2—, —NR17—, or —C(R18)2—.
Substitution-variable framework for formula (iv)
R1 and R2 are independently selected from the defined group classes and may be taken together with the nitrogen atom to form a heterocycloalkyl; further substituent variables R3 through R22 are defined by explicitly listed chemical-group options and optional substitution rules.
Cancer target limited to a defined set
The cancer is selected from lung cancer, melanoma, breast cancer, ovarian cancer, colorectal cancer, gastric cancer, gallbladder cancer, prostate cancer, renal cancer, multiple myeloma, and lymphoma.
The claim coverage centers on administering a Formula (IV) compound or pharmaceutically acceptable salt for treating cancer, with the inventive scope set by the Ring A, W, A, X, and broader R-group definitions, and the therapeutic indication limited to the listed cancers.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating cancer in a subject by administering a compound of Formula (IV), or a pharmaceutically acceptable salt thereof.
Inhibiting CD73 using the disclosed small molecules and related pharmaceutical compositions.
Treating infections and neurodegenerative diseases using the CD73 inhibitors and pharmaceutical compositions.
The cancer is selected from lung cancer, melanoma, breast cancer, ovarian cancer, colorectal cancer, gastric cancer, gallbladder cancer, prostate cancer, renal cancer, multiple myeloma, and lymphoma.
Interested in licensing this patent?