Cyclic dinucleotides as sting agonists
AssigneeJanssen Biotech, Inc.
InventorsStuart Emanuel, Mark Richter, Peter J. Connolly, James Patrick Edwards, Guangyi Wang, Santhosh Kumar Thatikonda, Leonid Beigelman, Minghong Zhong, Gilles Bignan, Wim Schepens, Marcel Viellevoye, Johannes Wilhelmus John Fitzgerald 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) as follows: wherein R, R1B, R1C, R2B, R2C, B1, W, X, Y, Z are defined herein.
Claims20
A compound of Formula (I):
- wherein:
- R is CH2;
- R1B is hydrogen, hydroxy, or fluoro;
- R1C is hydroxy, thiol, or BH3−;
- R2B is hydrogen, hydroxy, methoxy, or fluoro;
- R2C is hydroxy, thiol, or BH3−;
- B1 is rings b1, b2, b3, b4, b5, b6, b7 or b8
- W is —O— or —NH—;
- X is —O— or —NH—;
- Y is —CH2—, —O— or —NH—;
- Z is —CH2—, —O— or —NH—;
- wherein:
- (a) only one of X and Y is NH, and only one of W and Z is NH, in any instance;
- and
- (b) when B1 is b6 or b7, then R2B is other than fluoro or hydroxy;
- or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.
3-4. (canceled)
6-7. (canceled)
The compound of claim 7, wherein W and X are —O—;
- such that when B1 is b6, then R2B is other than fluoro or hydroxy.
The compound of claim 22, wherein B1 is b1, b2, b3, b4, b5, b6, or b8
A compound that is
- or a pharmaceutically acceptable salt form thereof.
A method of treating a disease, syndrome, or condition modulated by STING or affected by the agonism of STING, comprising administering to a subject in need thereof a therapeutically effective amount of a compound of formula (I):
- wherein:
- R is CH2 or O;
- R1B is hydrogen, hydroxy, or fluoro;
- R1C is hydroxy, thiol, or BH3−;
- R2B is hydrogen, hydroxy, methoxy, or fluoro;
- R2C is hydroxy, thiol, or BH3−;
- B1 is b1, b2, b3, b4, b5, b6, b7 or b8
- W is —O— or —NH—,
- X is —O— or —NH—,
- Y is —CH2—, —O— or —NH—,
- Z is —CH2—, —O— or —NH—,
- wherein:
- (a) wherein only one of X and Y is NH, and only one of W and Z is NH, in any instance;
- (b) when R is CH2 and B1 is b6 or b7, then R2B is other than fluoro or hydroxy;
- and
- (c) the compound of Formula (I) is other than a compound wherein R, W, X, Y, and Z, are each O;
- R1B and R2B are each hydroxy;
- B1 is b1;
- and R1B and R2B are each hydroxy;
- or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.
A compound of Formula (I):
- wherein:
- R is O;
- R1B is hydrogen, hydroxy, or fluoro;
- R1C is hydroxy, thiol, or BH3−;
- R2B is hydrogen, hydroxy, methoxy, or fluoro;
- R2C is hydroxy, thiol, or BH3−;
- B1 is b1, b2, b3, b4, b5, b6, b7 or b8:
- W is —O— or —NH—;
- X is —O— or —NH—;
- Y is —CH2—, —O— or —NH—;
- Z is —CH2—, —O— or —NH—;
- wherein:
- (a) only one of X and Y is NH, and only one of W and Z is NH, in any instance;
- (b) the compound of Formula (I) is other than a compound wherein W, X, Y, and Z, are each O;
- R1B and R2B are each hydroxy;
- B1 is b1;
- and R1B and R2B are each hydroxy;
- and
- (c) the compound of Formula (I) is other than a compound wherein:
- R1B is hydrogen, hydroxy, or fluoro;
- (i) R1C and R2C are hydroxy;
- (ii) R1C is hydroxy and R2C is thiol;
- or (iii) R1C is thiol and R2C is hydroxy;
- R2B is hydrogen, hydroxy, methoxy, or fluoro;
- B1 is b6:
- W is —O—;
- X is —O— or —NH—;
- Y is —CH2—, —O— or —NH—;
- Z is —CH2—, —O— or —NH—;
- provided that only one of X and Y is NH;
- or an enantiomer, diastereomer, or pharmaceutically acceptable salt form thereof.
Dependencies are inferred from the claim text.