Therapeutic compounds and compositions
Inventors
Salituro, Francesco G. • Saunders, Jeffrey O. • Yan, Shunqi
Assignees
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Publication Number
US-11866411-B2
Publication Date
2024-01-09
Expiration Date
Abstract
Compounds and compositions comprising compounds that modulate pyruvate kinase M2 (PKM2) are described herein. Also described herein are methods of using the compounds that modulate PKM2 in the treatment of cancer.
Core Innovation
The disclosure provides a family of quinoline-8-sulfonamide derivatives and related sulfonamide-containing piperazine analogs, including piperazine-1-carbonyl, homopiperazine, and diazepane-linked scaffolds. The compounds vary in aryl, benzyl, and heteroaryl substituents, including benzoyl, heterobenzoyl, nicotinoyl, isonicotinoyl, picolinoyl, fluorophenylpropanoyl, naphthoyl, thiophene-2-ylpropanoyl, thiazole and thiadiazole carbonyl motifs, and related substituted groups. The material is presented as a structurally diverse set of discrete compounds within the quinoline-8-sulfonamide family.
The structural series is reported with analytical characterization, including 1H NMR, HPLC purity, and LCMS values expressed as m/z (M+1) or related ions. The disclosure includes examples of chemical structures and names across multiple compound sets, with substituent variation on the piperazine-1-carbonyl, benzyl, phenyl, and quinoline-8-sulfonamide portions. The compounds are described as a common quinoline-8-sulfonamide core with amide products and salt forms.
The patent content also describes compounds of formula (I) or pharmaceutically acceptable salts thereof, defined by variable structural elements W, X, Y, Z, D, D1, A, and L, together with substituent classes R1, R3, Ra, Rb, Rc, and Rd and indices n, m, h, and g. The disclosed formula (I) scaffold uses an optionally substituted bicyclic heteroaryl group A and a selectable linker group L, with dependent claims narrowing W through Z, D and D1, and L, and adding pharmaceutical composition context.
Claims Coverage
The provided independent claims center on two formula (I) compound claims, each covering a pharmaceutically acceptable salt and a structurally defined scaffold with variable heteroatom selections, core attachment options, a bicyclic heteroaryl group A, and a multi-option linker L. Across the independent claims, the inventive features are organized around the same structural framework, with explicit substituent classes and index constraints, and dependent claims further narrow key selections.
Compound of formula (I) with variable heteroatoms and linker classes
A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein W, X, Y and Z are each independently selected from CH or N; D and D1 are independently selected from a bond or NRb; A is optionally substituted bicyclic heteroaryl; L is selected from a bond or specified linkage structures; R1 is selected from alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl with 0-5 occurrences of Rd; and R3, Ra, Rb, Rc, Rd, n, m, h, and g are defined by the stated options and values.
Compound of formula (I) with fixed heteroatom selections and narrowed index values
A compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein W, X, Y and Z are each CH in dependent narrowing; D is NRb and D1 is a bond; A is optionally substituted bicyclic heteroaryl; L is selected from specified bond/linkage options; R1 is selected from alkyl, cycloalkyl, aryl, heteroaryl, and heterocyclyl with 0-5 occurrences of Rd; and the indices are constrained such that h is 0 and g is 1 in one independent claim, and h is 1 and g is 0 in the other.
Pharmaceutical composition comprising the formula (I) compound
A pharmaceutical composition including the compound of formula (I) or a pharmaceutically acceptable salt of the compound.
Across the independent claims, coverage centers on a formula (I) scaffold with variable heteroatom assignments (W-Z), attachment options (D and D1), an optionally substituted bicyclic heteroaryl group A, and a restricted linker group L, together with defined substituent classes for R1, R3, Ra, Rb, Rc, and Rd and specified index ranges. Dependent claims further narrow W-Z to CH, fix D as NRb and D1 as a bond, limit L to specified alternatives, and include pharmaceutical composition embodiments.
Stated Advantages
Analytical confirmation of identity and purity of the synthesized quinoline-8-sulfonamide derivatives using 1H NMR, HPLC purity, and LCMS.
Documented Applications
Analytical characterization of synthesized quinoline-8-sulfonamide derivatives, including confirmation of identity and purity using 1H NMR, HPLC, and LCMS.
Pharmaceutical composition coverage including the claimed compound of formula (I) or a pharmaceutically acceptable salt.
Generation of quinoline-8-sulfonamide amide products and salt forms, including reported HPLC purity and MS data.
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