Compounds and compositions for treating conditions associated with STING activity

Inventors

Roush, William R. • Venkatraman, Shankar • Glick, Gary • Seidel, Hans Martin

Assignees

Novartis Pharma AG

Abstract

This disclosure features chemical entities of formula I (e.g., a compound or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that inhibit (e.g., antagonize) Stimulator of Interferon Genes (STING). Said chemical entities are useful, e.g., for treating a condition, disease or disorder in which increased (e.g., excessive) STING activation (e.g., STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions containing the same as well as methods of using and making the same.

Core Innovation

The invention relates to compounds of Formula (I), or pharmaceutically acceptable salts thereof, or N-oxides thereof. The compounds include an aromatic ring that includes Z, Y1, Y2, Y3, and Y4, with Z is CH, Y1 and Y2 are independently selected from CR1, Y3 is N, Y4 is C, X1 is NR2, and X2 is CH. The five-membered ring comprising Y4, X1, and X2 is heteroaryl, and the ring that includes Z, Y1, Y2, Y3, and Y4 is aromatic.

The Formula (I) further defines W as selected from C(=O), C(=S), C(=NRd), and C(=NH). The Q-A fragment is defined according to (A) or (B), where Q is NH or N(C1-6 alkyl), and A is defined through an (YA1)n-YA2 pattern with n=0 or through an alternative chain pattern, with YA2 selected from cycloalkyl, aryl, heteroaryl, or heterocyclyl groups subject to ring-atom, heteroatom, and optional substitution limits. In the (B) definition, Q and A taken together form a structure attached to W and include a ring E with defined ring-atom and heteroatom constraints.

The invention also includes extensive substituent definitions for R1, R2, Ra, Rb, Rc, Rd, Re, Rf, Rg, and R′/R″, including options for ring formation with attached nitrogen atoms. A conditional limitation applies when Q-A is defined according to (A) and A is C6 aryl mono-substituted with C4 alkyl, requiring that the ring including Z, Y1, Y2, Y3, and Y4 be substituted with one or more R1 other than hydrogen.

Claims Coverage

Two independent claim themes are present: a broad Formula (I) compound claim and a separate claim selecting compounds from a listed group of Final Structure compounds. The Formula (I) claim includes three main inventive features: the aromatic heteroaryl ring scaffold, the W substituent definition, and the Q-A fragment definition with a conditional substitution proviso.

The claim coverage is directed to Formula (I) compounds built around an aromatic heteroaryl five-membered ring, W selected from specified carbonyl/thiocarbonyl/amido-derived forms, and a Q-A fragment defined by either (A) or (B), with a conditional non-hydrogen substitution requirement in one branch. The partial content also includes a separate claim directed to selected listed final structure compounds.

Stated Advantages

Documented Applications