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US 11,597,746 B2Granted
Cyclic dinucleotides as sting agonists
AssigneeJanssen Biotech, Inc.
InventorsStuart Emanuel, Mark Richter, Peter J. Connolly, James P. Edwards, Guangyi Wang, Santhosh Kumar Thatikonda, Leonid Beigelman, Gilles Bignan, Wim Bert Griet Schepens, Marcel Viellevoye, Johannes Wilhelmus J. F. Thuring
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Abstract
Disclosed are compounds, compositions and methods for treating of diseases, syndromes, or disorders that are affected by the modulation of STING. Such compounds are represented by Formula (I), wherein R1, R1′, X1, B1, R2, R2′, B2, X2, R3, Z-M-Y, and Y1-M1-Z1 are as defined herein.
Claims53
A compound of Formula (I):
- wherein
- B1 and B2 are, independently, b1, b2, b3, b4, b5, b6, b7, b8, b9, b10, b11, b12, b13, b14, b15, b16, b17, b18, b19, b20, b21, b22, b23, b24, b25, b26, b27, b28, b29, or b30:
- R1 is hydrogen;
- hydroxy;
- fluoro;
- optionally substituted C1-3alkoxy;
- C3-6alkenyloxy;
- C2-6alkynyloxy;
- hydroxy(C1-3alkoxy);
- or optionally substituted C1-3alkyl;
- R1′ is hydrogen, fluoro, or hydroxy;
- provided that when R1′ is fluoro, R1 is hydrogen or fluoro;
- R2 is hydrogen;
- hydroxy;
- fluoro;
- optionally substituted C1-3alkoxy;
- C3-6alkenyloxy;
- C2-6alkynyloxy;
- hydroxy(C1-3alkoxy);
- or optionally substituted C1-3alkyl;
- and R3 is hydrogen;
- or, R3 is —CH2—, and R2 is —O—;
- such that R2, R3 and the atoms to which they are attached form a 5-membered ring;
- R2′ is hydrogen, fluoro, or hydroxy;
- provided that when R2′ is fluoro, R2 is hydrogen or fluoro;
- R3 hydrogen, fluoro, CH3, or CH2F;
- X1 and X2 are, independently, O, S, or CH2;
- L and L1 are, independently, —CH2— or —CH2CH2—;
- Y and Y1 are, independently, absent, 0, or NH;
- Z and Z1 are, independently, 0 or NH;
- one of M and M1 is
- and the other of M and M1 is
- or
- wherein:
- (i) when M is
- one of Y and Z is NH, and the other of Y and Z is O;
- and
- (ii) when M1 is
- one of Y1 and Z1 is NH, and the other of Y1 and Z1 is O;
- (iii) when Y is absent, L is —CH2CH2, and M is
- and
- (iv) when Y1 is absent, L1 is absent, and M1 is
- R4 is hydroxy, methyl, BH3, or —SR5;
- wherein:
- R5 is hydrogen, —CH2OC(O)R6, —CH2OC(O)OR6, —CH2CH2SC(O)R6, or —CH2CH2S—SCH2R6;
- and
- R6 is C6-10aryl, heteroaryl, heterocycloalkyl, C3-12cycloalkyl, or optionally substituted C1-20alkyl;
- or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.
45 more elements
A compound that is:
- or a pharmaceutically acceptable salt form thereof.
Dependencies are inferred from the claim text.