Compound, α-synuclein aggregate binder, and use thereof
Inventors
Higuchi, Makoto • Ono, Maiko • Cho, Meiei • Yamamoto, Takeshi • Wakabayashi, Takeshi
Assignees
Ono Pharmaceutical Co Ltd • Eisai R&D Management Co Ltd • Takeda Pharmaceutical Co Ltd • National Institutes For Quantum Science and Technology
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Publication Number
US-12630544-B2
Publication Date
2026-05-19
Expiration Date
Abstract
An embodiment of the present invention relates to a compound represented by formula (I) or (II), a pharmaceutically acceptable salt thereof, or a solvate thereof.
Core Innovation
The invention provides compounds represented by formula (I) or (II), including pharmaceutically acceptable salts or solvates, that function as b1-synuclein aggregate binding agents. The disclosure includes benzothiazole-linked compounds, radioisotope-containing variants, and fluorescent labeling for optical imaging and radioisotope labeling for radiological imaging.
The disclosure addresses the need for b1-synuclein aggregate imaging probes with sufficient affinity and selectivity, contrasting with prior PET probe [11C]BF-227 as having insufficient affinity/selectivity and off-target amyloid-b2 binding. The compounds are presented as improving binding selectivity for b1-synuclein aggregates relative to tau and amyloid-b2 aggregates.
A benzothiazole-linked intermediate represented by formula (III) is also provided for synthesizing the claimed compounds. The documented disclosure includes optical and radiological imaging use formats, including brain imaging of a living subject and radiological imaging compositions for detecting b1-synuclein aggregates.
Claims Coverage
The independent claims cover 6 inventive features across compounds, imaging uses, and an intermediate.
Compound of formula (I) or (II) with pharmaceutically acceptable salts or solvates
A compound represented by formula (I) or (II), a pharmaceutically acceptable salt thereof, or a solvate thereof.
Radioisotope-containing compound of formula (I) or (II)
A compound represented by formula (I) or (II), or its pharmaceutically acceptable salt or solvate, including radioisotopes as one or more atoms.
Alpha-synuclein aggregate binding agent
An b1-synuclein aggregate binding agent that is a compound, or a pharmaceutically acceptable salt or solvate of that compound.
Optical imaging method using first and second different wavelengths
A method for optical imaging of b1-synuclein aggregates in the brain of a living subject by externally irradiating the brain with light at a first wavelength, administering an b1-synuclein aggregate binding agent, and detecting emitted light from the brain at a second, different wavelength.
Radiological imaging composition for detecting alpha-synuclein aggregates
A radiological imaging composition for detecting b1-synuclein aggregates, where the composition includes an b1-synuclein aggregate binding agent.
Benzothiazole-linked intermediate of formula (III) with defined substituents
An intermediate being a benzothiazole-linked compound defined by formula (III), where X/Y are N and CH in either order, R1 is hydroxy or the group of formula (i), * indicates the benzothiazole ring binding position, and R2 is hydrogen or Boc.
Overall, the claim coverage centers on benzothiazole-linked b1-synuclein aggregate binding compounds of formula (I) or (II) including salts, solvates, and radioisotope-containing variants, and extends to optical imaging, radiological imaging compositions, and a defined intermediate of formula (III).
Stated Advantages
Improved binding selectivity for b1-synuclein aggregates relative to tau and amyloid-b2 aggregates.
Addresses limitations of prior PET probe [11C]BF-227 described as having insufficient affinity/selectivity and off-target amyloid-b2 binding.
Documented Applications
Optical imaging of b1-synuclein aggregates in the brain of a living subject using first and second different wavelengths.
Radiological imaging composition use for detecting b1-synuclein aggregates.
In vivo radiological imaging using PET, SPECT, and autoradiography as described in the disclosure.
Optical imaging modalities described in the disclosure including fluorescence, multiphoton, two-photon, and near infrared fluorescence.
Optical binding in human DLB versus AD tissue.
Binding in b1-synuclein fibril mouse and marmoset models.
In vivo two-photon fluorescence.
In vivo PET using [18F]SPAL-T-06, including biodistribution/accumulation and imaging capability.
In vitro binding and autoradiography demonstrating high-affinity b1-synuclein lesion selectivity and comparison to other protein aggregates.
Use of the benzothiazole-linked intermediate (formula III) for synthesizing the compound represented by formula (I)/(II).
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