Naphthofuran derivatives, preparation, and methods of use thereof
Inventors
ARUMUGASAMY, Jeevanandam • Li, Wei
Assignees
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Publication Number
US-11299469-B2
Publication Date
2022-04-12
Expiration Date
Abstract
Provided herein are methods of preparation of I by reacting i with acid where R1 and R2 are each independently a leaving group. Intermediates to make i are also claimed.
Core Innovation
The invention relates to a method of making a compound having formula (I), or a prodrug, a pharmaceutically acceptable salt, or a solvate thereof. The method comprises reacting a compound having formula (i), or a salt or solvate thereof, with an acid, wherein R1 and R2 are each independently a leaving group. The framework of formulas (i), (ii), (iii), and (iv) defines the reactants and intermediates used to reach compound of formula (I).
The document further describes conversion steps that connect specific intermediate structures, including converting a 2-hydroxynaphthalene-1,4-dione compound of formula (iv) into a compound of formula (ii). It also defines compounds having formula (ii-a) through (ii-i) and related variants, with substituent groups including hydrogen and classes of substituted and unsubstituted alkyl, alkenyl, alkynyl, cycloalkyl, heterocycle, and aryl groups, together with carbonyl, thiocarbonyl, sulfone, phosphoryl, and amide-like substituent patterns.
The document states that the compounds can be present as salts and solvates, including hydrates. It also describes preparation and handling of compound of formula (I) in terms of reaction solutions, including anisole, optionally silica gel as an agent, and specified temperature ranges used across the described conversions and solvent systems.
Claims Coverage
The independent claim covers a method of making a compound of formula (I) (or a prodrug, pharmaceutically acceptable salt, or solvate) by reacting a compound of formula (i) with an acid, where R1 and R2 are leaving groups. Dependent claims refine the acid selection, add an intermediate conversion from formula (iv) to formula (ii), and specify a base selection for reacting formula (ii).
Making formula (I) via acid reaction of a leaving-group substituted formula (i)
A method of making a compound having formula (I) (or a prodrug, a pharmaceutically acceptable salt, or a solvate thereof), comprising reacting a compound having formula (i) (or a salt or solvate thereof) with an acid, wherein R1 and R2 are each independently a leaving group.
Acid selected from named inorganic acids
The method where the acid is selected from sulfuric, phosphoric, nitric, perchloric, hydrofluoric, hydrochloric, hydrobromic, and hydroiodic acids.
Acid selected from sulfuric, phosphoric, or hydrochloric acid
The method where the acid is sulfuric acid, phosphoric acid, or hydrochloric acid.
Acid selected from named organic acids or anhydrides
The method where the acid is selected from formic acid, acetic acid, acetic anhydride, trifluoroacetic acid, trifluoroacetic anhydride, chloroacetic acid, or chloroacetic anhydride.
Intermediate conversion from formula (iv) to formula (ii)
The method further comprises converting a 2-hydroxynaphthalene-1,4-dione compound of formula (iv) (or one of its salts or solvates) into a compound of formula (ii).
Base selected from carbonate, phosphate, alkoxide, or amine bases
The method further comprises reacting the compound having formula (ii) in the presence of a selected base chosen from carbonate, phosphate, alkoxide, or amine bases.
Overall, the claim coverage centers on acid-mediated reaction of a formula (i) compound bearing leaving groups R1 and R2 to form compound of formula (I), with dependent refinements specifying particular acids, a conversion from formula (iv) to formula (ii), and a base category for reacting formula (ii).
Stated Advantages
Reported targeting of cancer stem cells.
Inhibition of STAT3 signaling.
Potential selectivity versus normal cells.
Documented Applications
Use of naphthofuran compounds as reported anticancer agents targeting cancer stem cells and inhibiting STAT3 signaling.
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