Modulators of cystic fibrosis transmembrane conductance regulator
Inventors
Clemens, Jeremy J. • Bookser, Brett C. • Cleveland, Thomas • Coon, Timothy R. • Gallant, Michel • Grootenhuis, Peter Diederik Jan • Hadida Ruah, Sara Sabina • Laterreur, Julie • Melillo, Vito • Miller, Mark Thomas • Paraselli, Prasuna • Ramtohul, Yeeman K. • Reddy, Thumkunta Jagadeeswar • Sturino, Claudio • Valdez, Lino • Zhou, Jinglan • Baek, Minson • Schulz Bechara, William
Assignees
Vertex Pharmaceuticals San Diego LLC • Vertex Pharmaceuticals Inc
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Publication Number
US-12269831-B2
Publication Date
2025-04-08
Expiration Date
Abstract
This disclosure provides modulators of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), pharmaceutical compositions containing at least one such modulator, methods of treatment of cystic fibrosis using such modulators and pharmaceutical compositions, and processes for making such modulators.
Core Innovation
The invention relates to compounds of Formula I and deuterated derivatives thereof, together with pharmaceutically acceptable salts. The structural scope is defined by selections for X, Y, Ring B, Ring C, Z, RZ1, RZ2, RZ3, n, and m, and includes stereochemical and configurational variants, enantiomer 1/2, diastereomer 1/2, E/Z mixtures, regiospecific and regioisomeric variants, and illustrated compound structures.
The disclosure also includes a compound of a formula, a deuterated derivative thereof, or a pharmaceutically acceptable salt of any of the foregoing. The provided content identifies specific fluorinated heterocycle and triazatricyclo compound examples, including stereochemical variants, enantiomers, diastereomers, regioisomeric diastereomers, deuterated forms, heptane solvates, and hydrochloride salt forms.
The compounds further encompass crystalline or solid forms, preparation and characterization of specific compound members, and pharmaceutical compositions containing a pharmaceutically acceptable carrier and optional additional therapeutic agents. The claims and described embodiments together frame a broad compound genus centered on Formula I chemical matter with deuterated derivatives and pharmaceutically acceptable salts.
Claims Coverage
Two independent claim groupings are present: one defines a broad Formula I compound genus with deuterated derivatives and pharmaceutically acceptable salts, and the other defines a compound of a formula, also including deuterated derivatives and pharmaceutically acceptable salts. In total, the independent claim coverage centers on extensive structural definitions for Formula I and a separate formula-based compound scope, with dependent claims further addressing pharmaceutical compositions and cystic fibrosis treatment.
Formula I compound genus with constrained heteroatom, linker, ring, and substituent sets
A compound selected from compounds of Formula I, and deuterated derivatives and pharmaceutically acceptable salts thereof, wherein X is selected from —O—, —S—, —SO—, and —SO2—; each Y is independently selected from —C(RY)2—, —O—, and —CO—; each RY is independently selected from hydrogen, halogen, C1-C6 alkyl, C3-C8 cycloalkyl, C6-C10 aryl, 5- to 10-membered heteroaryl, and additional substituted or ring-forming options; Ring B is selected from C6-C10 aryl, C3-C8 cycloalkyl, 5- to 10-membered heteroaryl, and 3- to 6-membered heterocyclyl; each Q is independently selected from defined C1-C6 alkyl and substituted aryl, cycloalkyl, heteroaryl, and heterocyclyl options; Ring C is selected from C6-C10 aryl and 5- to 10-membered heteroaryl; and n and m are selected from the specified integer ranges.
Formula-defined compound including deuterated derivatives and pharmaceutically acceptable salts
A compound of the formula, a deuterated derivative thereof, or a pharmaceutically acceptable salt of any of the foregoing.
The claim coverage is dominated by a structurally constrained Formula I genus that explicitly includes deuterated derivatives and pharmaceutically acceptable salts, together with a second formula-based compound claim of the same type. The dependent claim family further links the compounds to pharmaceutical compositions and to treatment of cystic fibrosis.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Pharmaceutical compositions comprising the compound, deuterated derivative, or pharmaceutically acceptable salt and a pharmaceutically acceptable carrier, optionally with additional therapeutic agents.
A method of treating cystic fibrosis by administering an effective amount of the compound, deuterated derivative, or pharmaceutically acceptable salt.
CFTR-modulating therapeutic use context, including references to CFTR corrector and CFTR potentiator/enhancer categories and named CFTR-modulating agents in composition embodiments.
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