Alkyl chain modified imidazoquinoline TLR7/8 agonist compounds and uses thereof

Inventors

Chipman, Stewart D. • Kiwan, Radwan • KACHURA, Melissa A. • Coffman, Robert

Assignees

Dynavax Technologies Corp

Abstract

Disclosed are alkyl chain modified 1H-imidazoquinoline compounds, derivatives and analogs thereof, as Toll-like receptor-7 and -8 agonists for enhancing immune responses. Also provided are methods of making pharmaceutical compositions containing these compounds. The present disclosure also describes methods of use for the alkyl chain modified 1H-imidazoquinoline compounds, derivatives and analogs thereof, and pharmaceutical compositions containing these compounds for the treatment of disease in a subject.

Core Innovation

The invention relates to using a pharmaceutical composition for treating cancer in a mammalian subject in need thereof. The composition comprises a compound of formula (J), or a salt thereof, together with a pharmaceutically acceptable excipient, and is administered in an amount sufficient to treat the cancer. The scope of formula (J) is defined through specific structural variables, including R0, m, z, RA, X, R1, R2, R3, q, R4a, and R4b.

The compound of formula (J) is characterized by constrained substituent structures in which R0 is either a (CH2)z(C(CH3)2)RA group or a (CH2)mRA group. m is limited to 0, 1, 2, or 3, and z is limited to 1 or 2. RA is defined as C3-C8 cycloalkyl optionally substituted by 1 to 4 groups selected from C1-C4 alkyl, C1-C4 alkylene, and halogen, and X is defined as —NH—.

Further structural constraints specify that R1 is C3-C6 alkyl or substituted (CH2)p groups with allowed OR1a, NHR1b, or R1c patterns, with R1a and R1b independently being C1-C3 alkyl and R1c being C3-C4 cycloalkyl. R2 is NHR2a where R2a is H, OH, NH2, or methyl, and each R3 is independently halogen, C1-C8 alkyl, —(C1-C7 alkylene)NH2, or —CH2-phenylene-CH2NH2. q is limited to 0, 1, 2, 3, or 4, and R4a and R4b are independently H or C1-C8 alkyl.

Claims Coverage

The provided independent claim is directed to a method of treating cancer in a mammalian subject by administering a pharmaceutical composition comprising a compound of formula (J) or a salt thereof and a pharmaceutically acceptable excipient. The inventive features are centered on the specified formula (J) substituent definitions together with the cancer-treatment composition-administering method.

Across the single provided independent claim, the coverage is centered on administering a cancer-treating pharmaceutical composition comprising a compound of formula (J) or a salt thereof together with a pharmaceutically acceptable excipient, while using the constrained structural variables and substituent option sets defined for formula (J).

Stated Advantages

Documented Applications