Compounds, compositions, and methods for the treatment of disease
Inventors
Iyer, Radhakrishnan P. • Padmanabhan, Seetharamaiyer • Baskaran, Subramanian • Sheri, Anjaneyulu • Cleary, Dillon • MASTROLIA, RON • Zhou, Shenghua • Challa, Sreerupa • Gimi, Rayomand H. • NAIR, VISHAL • SUPPIAH, LEENA PRABA
Assignees
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Publication Number
US-12667573-B2
Publication Date
2026-06-30
Expiration Date
Abstract
Disclosed are compounds and compositions for inhibiting the expression of a pattern recognition receptor (e.g., STING), and methods of use thereof.
Core Innovation
The invention is directed to compounds of formula I, or pharmaceutically acceptable salts thereof. The formula includes M being Cl or F and Z being SR1, SO2R1, or N(R1)(R2), with R1 and R2 each independently H or alkyl. R3 is selected from H, alkyl, methyl, haloalkyl, chloromethyl, alkyloxyalkyl, methoxymethyl, hydroxyalkyl, hydroxymethyl, aminoalkyl, diethylamino, aryl, phenyl, alkynyl, ethynyl, and substituted variants including heterocyclylalkyl or morpholinylalkyl.
The structure further includes L1 as C7-C15 alkyl, each R4 independently selected from halo, CN, SR7, OR7, NHCOR7, NR8CO2R7, N(R7)(R8), COR7, CO2R7, OC(O)R7, CON(R7)(R8), heteroaryl, or heterocyclyl, and n as an integer from 0-18. The disclosure describes substituted chlorinated heteroaromatic and purine-like scaffold derivatives with long aliphatic chains and variable terminal functional groups, including carboxylic acid, ester, alcohol, amide, nitrile, sulfoxide, and sulfone variants.
The document also presents specific numbered compounds as selected members of the formula I space, with structures shown as chlorinated bicyclic heteroaromatic cores bearing different side-chain and terminal-group substitutions. Some examples are described with sulfur-containing motifs and heterocycle-containing substituents, and the examples are characterized by LCMS and 1H NMR.
Claims Coverage
The claims cover a broad Formula I compound genus and a separate selection of specifically numbered compounds. The Formula I coverage includes multiple inventive features defined by variable substituents, a C7-C15 alkyl linker, and n from 0-18, while the selected-compound claim covers a defined group of numbered structures.
Formula I compound with variable halogen and Z substituent pattern
A compound of formula I, or a pharmaceutically acceptable salt thereof, wherein M is Cl or F, Z is SR1, SO2R1, or N(R1)(R2), and R1 and R2 are each independently H or alkyl.
Broad R3 substituent enumeration
R3 is selected from H, alkyl, methyl, haloalkyl, chloromethyl, alkyloxyalkyl, methoxymethyl, hydroxyalkyl, hydroxymethyl, aminoalkyl, diethylamino, aryl, phenyl, alkynyl, ethynyl, alkyne substituted with cycloalkyl, heterocyclylalkyl or morpholinylalkyl.
C7-C15 alkyl linker and R4 substituent options
L1 is C7-C15 alkyl, each R4 is independently halo, CN, SR7, OR7, NHCOR7, NR8CO2R7, N(R7)(R8), COR7, CO2R7, OC(O)R7, CON(R7)(R8), heteroaryl, or heterocyclyl, and R7 and R8 are each independently selected from hydrogen and alkyl.
Integer parameter n from 0-18
The compound of formula I is defined with n as an integer from 0-18.
Selected compounds identified by compound number
A compound selected from the group consisting of compound numbers 9, 24, 28, 69, 74, 96, 97, 109, 111, 112, 114, 118, 121, 122, 124, 125, 128, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 142, 143, 144, 145, 146, 147, 148, 149, 150, 152, 158, 159, 160, 162, 164, 165, 167, and 168.
Overall, the claims cover a Formula I structural framework defined by M, Z, R1/R2, R3, L1, R4, and n, together with a separate claim directed to a specified set of numbered compounds.
Stated Advantages
Documented Applications
STING antagonism evaluation using THP-1 and RAW reporter assays, including pathway comparisons for cGAS-STING-IRF/NF-κB and RIG-I-IRF/NF-κB versus TLR7/9.
Activity and stability assessment referenced through IC50 reporting and simulated gastric/intestinal fluids with HPLC analysis.
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