Spiro[benzo[d]thiazole-6 ,4′-piperidine as ACC inhibitors
Inventors
BAGLEY, SCOTT WILLIAM • Bootsma, Andrea Nicole • Choi, Chulho • Dow, Robert Lee • Edmonds, David James • Garcia-Irizarry, Carmen Noemi • GERSTENBERGER, Brian Stephen • Ingle, Gajendra • O'Brien, Jessica Gloria Katherine • Parikh, Mihir Dineshkumar • Rescourio, Gwenaella Christine • Schmitt, Daniel Copley
Assignees
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Publication Number
US-12655157-B2
Publication Date
2026-06-16
Expiration Date
Abstract
The invention relates to compounds of Formula (I), or a pharmaceutically acceptable salt thereof, or a pharmaceutically acceptable solvate of said compound or pharmaceutically acceptable salt; to compositions containing such compounds; and to the uses of such compounds in the treatment of various diseases, particularly acne.
Core Innovation
The disclosure provides tricyclic spiro[benzo[d]thiazole-piperidine] compounds of Formula (I), including ketone, alcohol, hydroxy, and deuterated forms, or pharmaceutically acceptable salts and solvates thereof. The compounds function as inhibitors of ACC1 and ACC2, defined by specific substituent selections for R and R1 with m and n independently selected as 0, 1, 2, or 3. Disclosed embodiments encompass indazole-, indole-, quinoline-, isoquinoline-, naphthalene-, and pyridine-derived compounds.
The compounds inhibit recombinant human acetyl-CoA carboxylase 1 and inhibit de novo lipogenesis in cultured human SZ95 sebocytes, reducing sebum production for treating acne. The compound series undergoes evaluation in a high-content imaging assay measuring reductions in neutral-lipid droplet number and area, exhibiting reported IC50 values; [procedural detail omitted for safety]. Metabolic profiling indicates oxidation and glucuronidation pathways, providing a rationale for proposed deuterated analogues intended to improve pharmacokinetic and tolerability profiles.
Claims Coverage
The provided claims identify one independent claim, claim 1, comprising two inventive features directed to the formula (I) compound genus.
Formula (I) compound and acceptable forms
A compound of formula (I), or a pharmaceutically acceptable salt thereof or pharmaceutically acceptable solvate of the compound or salt.
Defined substituents for R and R1
R is selected from H, C1-C6 alkoxy, C1-C6 alkyl, or —(CH2)m—W, with W selected from cycloalkyl, bicycloalkyl, bridged bicycloalkyl, phenyl, heteroaryl, or heterocyclic groups, and R1 is selected from phenyl, naphthyl, aryl, heteroaryl, or heterocyclic groups, with m and n independently being 0, 1, 2, or 3.
Claim 1 covers the defined formula (I) spiro compound genus and its acceptable salts and solvates, while associated dependent claims recite specific compounds, pharmaceutical compositions with excipients, and topical acne treatments.
Stated Advantages
The provided content proposes that deuteration may improve metabolic stability, in-vivo half-life, dosage requirements, CYP450 inhibition, therapeutic index, or tolerability; these benefits are not demonstrated in the provided content.
Documented Applications
The compounds, salts, or solvates are documented for reducing sebum production and treating acne.
The acne-treatment claims recite topical administration in dosage forms including creams, ointments, lotions, gels, solutions, suspensions, foams, aerosols, sprays, shampoos, patches, or tapes.
The compounds are documented for evaluation in a high-content imaging assay using human SZ95 sebocytes to determine effects on neutral-lipid droplets and establish IC50 values.
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