1-(2-(6-[18f]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-n-(pyrimidin-2-yl)-2,3-dihydro-1h-indene-5-sulfonamide and uses in pet imaging

Abstract

Disclosed herein is a PET tracer compound (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide and salts thereof, and uses of the same as imaging agents. Also disclosed are precursor compounds, such as (S)-1-(2-(6-nitropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide, and salts thereof. Also disclosed are kits comprising the same.

Description

[0001]779282.000028 1-(2-(6-[18F]FLUOROPYRIDIN-3-YL)-4-(TRIFLUOROMETHYL)PHENYL)-N- (PYRIMIDIN-2-YL)-2,3-DIHYDRO-1H-INDENE-5-SULFONAMIDE AND USES IN PET IMAGING RELATED APPLICATIONS This application claims the benefit of U.S. Provisional Application No.63 / 664,863, filed June 27, 2024, the entire contents of which are incorporated herein by reference. BACKGROUND Voltage-gated sodium channels contain a pore-forming alpha subunit and a stabilizing beta subunit. Multiple isoforms of the alpha subunit have been identified based on the similarity to amino acid sequences in the extracellular and transmembrane domain. The Voltage-gated sodium channel NaV 1.7 is prominently responsible to cause pain. Loss of function mutations in the human NaV 1.7 gene leads to congenital insensitivity to pain. Sodium ion channel (NaV)- targeted radioactive tracers are needed for developing methods for diagnosing and identifying therapies for Nav related diseases, such as pain, epilepsy, seizures, movement disorders and neurological disorders. Barbieri et al. reported voltage-gated sodium channel dysfunctions in neurological disorders. (Life (2023) 13:119). Hoyt et al. reported 3-amino-1,5-benzodiazepinones as potent, state-dependent sodium channel blockers with anti-epileptic activity. (Bioorganic & Medicinal Chemistry Letters (2008) 18:1963-1966). Ramdas et al. reported NaV 1.7 inhibitors with oral efficacy in pain models. (J. Med. Chem. (2020) 63:6107−6133; See also WO 2018 / 163077) Schoenberger et al. reported compounds useful as radiotracers for position emission tomography imaging of voltage gated sodium channels. (See US Patent No.11,117,858). References cited herein are not an admission of prior art. SUMMARY This disclosure relates to a tracer compound (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide, derivatives, 1 \\4158-6725-4109 v1 779282.000028 or salts thereof, and uses as a PET imaging agent. In certain embodiments, this disclosure relates to precursor compounds for generating (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide such as (S)- 1-(2-(6-nitropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H- indene-5-sulfonamide, derivatives, or salt thereof or salts thereof. In certain embodiments, this disclosure relates to methods comprising: a) administering a composition comprising the tracer compound (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide isotopically enriched with fluorine 18 to a subject; and scanning the subject for emissions from an area of the subject. In certain embodiments, the (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide tracer binds to or enters cells, tissues, or organs that express a voltage-gated sodium channel. In certain embodiments, the emissions are from on the exterior or inside a nerve. In certain embodiments, the (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide tracer is administered at a dose of 0.04 to 0.9 µmol / kg or 0.04 to 10 µmol / kg. In certain embodiments, scanning the subject for emissions is for between 15 and 30min of longer. In certain embodiments, administering is at a dose of about 0.9 µmol / kg and scanning the subject for emissions is for 15 min or more. In certain embodiments, methods further comprise the step of detecting and / or measuring the emissions and creating an image indicating or highlighting the location of the compound isotopically enriched with fluorine 18 in the subject. In certain embodiments, the emissions are from or on the exterior or inside a nerve. In certain embodiments, methods comprise the step of detecting, measuring, and / or quantifying the emission providing an emission quantity and optionally correlating the emission measurement / detection / quantity to a concentration of (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide on or in the cells, tissue, or organ. In certain embodiments, methods further comprise the step of correlating a low, high, or abnormal measurement, quantity, or concentration of (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide to the 2 \\4158-6725-4109 v1 779282.000028 existence of or diagnosis of a subject at risk of a pain, epilepsy, seizure, movement disorder, central nervous system disease, or condition. In certain embodiments, the disease is pain sensitivity or pain insensitivity, or a neurodegenerative disease. In certain embodiments, this disclosure relates to a PET imaging precursor compound (S)-1-(2-(6-nitropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H- indene-5-sulfonamide or salt thereof. In certain embodiments, this disclosure relates to methods of making the (S)-1-(2-(6- [18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene- 5-sulfonamide tracer comprising contacting a precursor compound (S)-1-(2-(6-nitropyridin-3- yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide with an isotopically enriched fluorine 18 negative ion producing the PET imaging tracer (S)-1-(2-(6- [18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene- 5-sulfonamide. In certain embodiments, the enriched fluorine 18 negative ion is a fluorine 18 potassium salt bound to a cryptand. In certain embodiments, this disclosure relates to kits comprising a precursor PET imaging compound disclosed herein and potassium ion bound to a cryptand. In certain embodiments, this disclosure relates to a growth medium comprising (S)-1-(2- (6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H- indene-5-sulfonamide tracer. In certain embodiments, the growth medium further comprises a cell, e.g., nerve cell or cell expressing a voltage-gated sodium channel gene, e.g., NaV l.7. BRIEF DESCRIPTION OF THE DRAWING FIG.1 shows data on whole-body biodistribution of (S)-1-(2-(6-[18F]fluoropyridin-3- yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide also referred to herein as [18F]15, in CD-1 mice. CD-1 mice were injected with [18F]15 via the tail vein and then the mice were divided into four groups and euthanized at different time point after the injection of [18F]15. Organs of interests were collected and weighted, and then counted by gamma counter. The percentage of injected dose per gram (%ID / g) was calculated as follows: %ID / g = tissue activity / injected dose x 100% 3 \\4158-6725-4109 v1 779282.000028 DETAILED DISCUSSION Before the present disclosure is described in greater detail, it is to be understood that this disclosure is not limited to particular embodiments described, and as such may, of course, vary. An "embodiment" of this disclosure refers to an example and infers that the example is not intended to be limiting. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. It will be understood that other methods and materials similar or equivalent to those described herein can also be used in the practice or testing of the present disclosure. All publications and patents cited in this specification are herein incorporated by reference as if each individual publication or patent were specifically and individually indicated to be incorporated by reference and are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited. The citation of any publication is for its disclosure prior to the filing date and should not be construed as an admission that the present disclosure is not entitled to antedate such publication by virtue of prior disclosure. Further, the dates of publication provided could be different from the actual publication dates that may need to be independently confirmed. As will be apparent to those of skill in the art upon reading this disclosure, each of the individual embodiments described and illustrated herein has discrete components and features which may be readily separated from or combined with the features of any of the other several embodiments without departing from the scope or spirit of the present disclosure. Any recited method can be carried out in the order of events recited or in any other order that is logically possible. Embodiments of the present disclosure will employ, unless otherwise indicated, techniques of medicine, organic chemistry, biochemistry, molecular biology, pharmacology, and the like, which are within the skill of the art. Such techniques are explained fully in the literature. Prior to describing the various embodiments, the following definitions are provided and should be used unless otherwise indicated. It must be noted that, as used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context clearly dictates otherwise. 4 \\4158-6725-4109 v1 779282.000028 In this specification and in the claims that follow, reference will be made to a number of terms that shall be defined to have the following meanings unless a contrary intention is apparent. As used herein, the term "about” means a range of values including the specified value, which a person of ordinary skill in the art would consider reasonably similar to the specified value. In embodiments, about means within a standard deviation using measurements generally acceptable in the art. In embodiments, about means a range extending to + / - a percentage of the specified value. In embodiments, about includes the specified value. In certain embodiments, the term “about” can include a 5 % or 10 % difference. As used in this disclosure and claim(s), the words "comprising" (and any form of comprising, such as "comprise" and "comprises"), "having" (and any form of having, such as "have" and "has"), "including" (and any form of including, such as "includes" and "include") or "containing" (and any form of containing, such as "contains" and "contain") have the meaning ascribed to them in U.S. Patent law in that they are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. "Consisting essentially of" or "consists of" or the like, when applied to methods and compositions encompassed by the present disclosure refers to compositions like those disclosed herein that exclude certain prior art elements to provide an inventive feature of a claim but may contain additional composition components or method steps, etc., that do not materially affect the basic and novel characteristic(s) of the compositions or methods. In certain embodiments, methods disclosed herein may make measurements that are compared to a normal or reference value. As used herein, a “reference value” can be an absolute value; a relative value; an average value; a median value, a mean value, or a value as compared to a particular control or baseline value. A reference value can be based on an individual sample or many samples, such as from patients or normal individuals. A “normalized measured” value refers to a measurement taken and adjusted to take background into consideration. Background subtraction to obtain total fluorescence is considered a normalized measurement. The background subtraction allows for the correction of background fluorescence that is inherent in the optical system and assay buffers. A “test compound” can be any variety of organic compounds such as small molecules, proteins, antibodies, nucleobases, nucleobase polymers, and known therapeutic agents or therapeutic candidates. 5 \\4158-6725-4109 v1 779282.000028 As used herein, the term “derivative” refers to a structurally similar compound that retains sufficient functional attributes of the identified analogue. The derivative may be structurally similar because it is lacking one or more atoms, substituted, a salt, in different hydration / oxidation states, or because one or more atoms within the molecule are switched, such as, but not limited to, replacing a oxygen atom with a sulfur atom, replacing an amino group with a hydroxyl group, replacing a nitrogen with a protonated carbon (CH) in an aromatic ring, replacing a bridging amino group (-NH-) with an oxy group (-O-), replacing a bridging amino group (-NH-) with an thio group (-S-), or vice versa. In certain embodiments, a derivative is an alkyl group substituted with a carbocyclyl, e.g., a propyl or butyl group substituted with corresponding a cyclopropyl or cyclobutyl group. The derivative may be a prodrug. Derivatives may be prepared by any variety of synthetic methods or appropriate adaptations presented in synthetic or organic chemistry textbooks, such as those provide in March's Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, Wiley, 6th Edition (2007) Michael B. Smith or Domino Reactions in Organic Synthesis, Wiley (2006) Lutz F. Tietze hereby incorporated by reference. In certain embodiments, a derivative is a compound disclosed herein substituted with a substituent. The term "substituted" refers to a molecule wherein at least one hydrogen atom is replaced with a substituent. When substituted, one or more of the groups are "substituents." The molecule may be multiply substituted. In the case of an oxo substituent ("=O"), two hydrogen atoms are replaced. Example substituents within this context may include halogen, hydroxy, thio, amine, alkyl, alkoxy, alkylamine, dialkyl amine, alkylthio, nitro, cyano, oxo, carbocyclyl, carbocycloalkyl, heterocarbocyclyl, heterocarbocycloalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, -NRaRb, -NRaC(=O)Rb, -NRaC(=O)NRaNRb, -NRaC(=O)ORb, - NRaSO2Rb, -C(=O)Ra, -C(=O)ORa, -C(=O)NRaRb, -OC(=O)NRaRb, -ORa, -SRa, -SORa, - S(=O)2Ra, -OS(=O)2Ra and -S(=O)2ORa. Ra and Rb in this context may be the same or different and independently hydrogen, halogen hydroxyl, alkyl, alkoxy, alkyl, amino, alkylamino, dialkylamino, carbocyclyl, carbocycloalkyl, heterocarbocyclyl, heterocarbocycloalkyl, aryl, arylalkyl, heteroaryl, and heteroarylalkyl. The term, "subject" refers to any animal, such as a human patient, livestock, e.g., horse, cow, pig, chicken, turkey, mouse, rodent, monkey, or other domestic pet dog or cat. In certain embodiments, the subject is a human (e.g., a human patient), a pregnant mother, an infant, a 6 \\4158-6725-4109 v1 779282.000028 child, an adult, a newborn (e.g., less than 1 years old), or an elderly adult (e.g., over 50, 60, or 65 years old). As used herein, the term “neurodegenerative disorder” refers to a disease or condition in which the function of a nervous system of a subject becomes impaired. Examples of contemplated neurodegenerative diseases include Alzheimer's disease, Alexander's disease, Alper's disease, amyotrophic lateral sclerosis, ataxia telangiectasia, Batten disease, bovine spongiform encephalopathy (BSE), chronic fatigue syndrome, corticobasal degeneration, Creutzfeldt-Jakob disease, frontotemporal dementia, Gerstmann-Sträussler-Scheinker syndrome, Huntington's disease, HIV-associated dementia, Kennedy's disease, Krabbe's disease, Lewy body dementia, Machado-Joseph disease, multiple sclerosis, multiple system atrophy, narcolepsy, neuroborreliosis, Parkinson's disease, Pelizaeus-Merzbacher Disease, Pick's disease, primary lateral sclerosis, Refsum's disease, Sandhoff's disease, Schilder's disease, schizophrenia, spinocerebellar ataxia, spinal muscular atrophy, Steele-Richardson-Olszewski disease, or progressive supranuclear palsy. The terms, “cell culture” or “growth medium” or “media” refers to a composition that contains components that facilitate cell maintenance and growth through protein biosynthesis, such as vitamins, amino acids, inorganic salts, a buffer, and a fuel, e.g., acetate, succinate, a saccharide / disaccharide / polysaccharide, medium chain fatty acids, and / or optionally nucleotides. Typical components in a growth medium include amino acids (histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, valine, and others); vitamins such as retinol, carotene, thiamine, riboflavin, niacin, biotin, folate, and ascorbic acid; carbohydrate such as glucose, galactose, fructose, or maltose; inorganic salts such as sodium, calcium, iron, potassium, magnesium, zinc; serum; and buffering agents. Additionally, a growth medium may contain a pH indicator, e.g., phenol red. Components in the growth medium may be derived from blood serum or the growth medium may be serum-free. The growth medium may optionally be supplemented with albumin, lipids, insulin and / or zinc, transferrin or iron, selenium, ascorbic acid, and an antioxidant such as glutathione, 2-mercaptoethanol or 1-thioglycerol. Other contemplated components contemplated in a growth medium include ammonium metavanadate, cupric sulfate, manganous chloride, ethanolamine, and sodium pyruvate. Various growth mediums are known in the art. For example, Minimal Essential Medium (MEM) is a term of art referring to a growth medium that contains calcium chloride, potassium 7 \\4158-6725-4109 v1 779282.000028 chloride, magnesium sulfate, sodium chloride, sodium phosphate and sodium bicarbonate, essential amino acids, and vitamins: thiamine (vitamin B1), riboflavin (vitamin B2), nicotinamide (vitamin B3), pantothenic acid (vitamin B5), pyridoxine (vitamin B6), folic acid (vitamin M), choline, and inositol (originally known as vitamin B8). Dulbecco's modified Eagle's medium (DMEM) is a growth medium which contains additional components such as glycine, serine, and ferric nitrate with increased amounts of vitamins, amino acids, and glucose. Animal serum such as fetal bovine serum (FBS) is sometimes added to a growth media as a supplement. “Positron emission tomography” (PET) refers to an imaging technique that produces an image, e.g., three-dimensional image, by detecting pairs of gamma rays emitted indirectly by a positron-emitting radionuclide tracer. Images of tracer concentration within the area are then constructed by computer analysis. A radioactive tracer is administered to a subject e.g., into blood circulation. Typically, there is a waiting period while tracer becomes concentrated in areas of interest; then the subject is placed in the imaging scanner. As the radionuclide undergoes positron emission decay, it emits a positron, an antiparticle of the electron with opposite charge, until it decelerates to a point where it can interact with an electron, producing a pair of (gamma) photons moving in approximately opposite directions. These are detected in a scanning device. The technique typically utilizes simultaneous or coincident detection of the pair of photons moving in approximately opposite direction. Photons that do not arrive in pairs (i.e., within a timing-window) are typically ignored. One typically localizes the source of the photons along a straight line of coincidence (also called the line of response, or LOR). This data is used to generate an image. The term "radionuclide" or "radioactive isotope" refers to molecules of enriched isotopes that exhibit radioactive decay (e.g., emitting positrons). Such isotopes are also referred to in the art as radioisotopes. A radionuclide tracer does not include radioactive primordial nuclides but does include naturally occurring isotopes that exhibit radioactive decay with an isotope distribution that is enriched, i.e., greater than natural abundance. In certain embodiments, it is contemplated that the radionuclides are limited to those with a half live of less than 1 hour and those with a half-life of more than 1 hour but less than 24 hours. Radioactive isotopes are named herein using various commonly used combinations of the name or symbol of the element and its mass number (e.g.,18F, F-18, or fluorine-18). 8 \\4158-6725-4109 v1 779282.000028 Such isotopically labeled compounds are useful in metabolic studies, reaction kinetic studies, detection, or imaging techniques [such as positron emission tomography (PET) or single- photon emission computed tomography (SPECT)] including drug or substrate tissue distribution assays. In particular, an18F or11C labeled compound can be used for PET or SPECT studies. One can produce [18F] fluoride by irradiation of water (containing H218O) with protons resulting in the18O(p,n)18F reaction. The [18F] isotope is then separated from water and processed for production of a radiopharmaceutical agent. Typically, fluoride recovery is based on ion exchange resins. Typically, the recovery is carried out in two steps (extraction and elution): first the anions (not only fluoride) are separated from the enriched [18O] water and trapped on a resin and then, said anions, including [18F] fluoride, are eluted into a mixture containing water, organic solvents, a base, also called activating agent or phase transfer agent or phase transfer catalyst, such as the complex potassium carbonate-Kryptofix 222TM(K2CO3-K222) or a tetrabutylammonium salt. Kryptofix 222TMis a cyclic crown ether, which binds the potassium ion, preventing the formation of18F–KF. Thus, potassium acts as the counter ion of18F–to enhance its reactivity but does not interfere with the synthesis. Typical labeling methods use low water content solutions. An evaporation step may follow the recovery of the [18F]fluoride, e.g., azeotropic evaporation of acetonitrile or other low boiling temperature organic solvent. Alternatively, the extraction process is performed by passing the [18F] aqueous solution on a solid support as reported in U.S. Patent 8,641,903. This solid support is typically loaded with a trapping agent, e.g., compound comprising a quaternary amine that is adsorbed on the solid support and allows the [18F] activity to be trapped because of its positive charge. The solid support is then flushed with a gas or a neutral solvent to remove or push out most of the residual water. The [18F] is eluted in an organic solvent or in a mixture of organic solvents and is usable for labelling of precursor compounds. Certain of the compounds described herein may contain one or more asymmetric centers and may give rise to enantiomers, diastereomers, and other stereoisomeric forms that can be defined, in terms of absolute stereochemistry at each asymmetric atom, as (R)- or (S)- or in terms of the ability to bend plan polarized light in the positive or negative direction. The present chemical entities, compositions and methods are meant to include all such possible isomers, including racemic mixtures, tautomer forms, hydrated forms, optically substantially pure forms, and intermediate mixtures. 9 \\4158-6725-4109 v1 779282.000028 In certain embodiments, this disclosure relates to methods of making compounds disclosed herein comprising contacting a starting material with reagents reported herein under conditions that the products are formed as reported herein. In certain embodiments, methods further comprise purifying and isolating the desired product e.g., by recrystallization or chromatographic methods. In certain embodiments, this disclosure relates to a compound disclosed herein with greater than 70%, 80%, 90%, 95%, of 97% purity by weight. In certain embodiments, if the product has a chiral center, the product may be purified to greater than 70%, 80%, 90%, 95%, of 97% enantiomeric excess or diastereomeric excess. Methods of Use In certain embodiments, a compound disclosed herein comprising a radionuclide is administered to a subject, and the radionuclide in the subject is used to create an image. The radionuclide can be administered at any suitable dose. The subject can be imaged using any suitable imaging apparatus, for example an apparatus capable of gathering a magnetic resonance image (MRI), a positron emission tomography (PET) scan, or a computed tomography (CT) scan. In certain embodiments, methods entail administering to a subject (which can be human or animal, for experimental and / or diagnostic purposes) an image-generating amount of a compound of the disclosure, labeled with the appropriate isotope and then measuring the distribution of the compound by PET. An image-generating amount is that amount which is at least able to provide an image in a PET scanner considering the detection sensitivity and noise level of the scanner, the age of the isotope, the body size of the subject and route of administration. Methods disclosed herein may be combined with other methods such as single photon emission computed tomography (SPECT) scans, computerized tomography (CT) scans, and MRI. A CT scan combines a series of X-ray images taken from different angles uses computer processing to create cross-sectional images, or slices of the brain, bones, blood vessels and soft tissues inside a body. These scans or associated data can be used to create computerized images that take place in tissue. A scanner records data, and a computer constructs two- or three- dimensional images. 10 \\4158-6725-4109 v1 779282.000028 It should be noted that the amount effective to result in uptake of the tracer compound into the cells or tissue of interest will depend upon a variety of factors, including for example, the age, body weight, general health, sex, and diet of the host; the time of administration; the route of administration; the rate of excretion of the specific compound employed; the duration of the treatment; the existence of other drugs used in combination or coincidental with the specific composition employed; and like factors. Imaging methods provided by the present disclosure include the use of the radionuclide containing compounds of the present disclosure and / or salts thereof that can generate at least a 2:1 target to background ratio of radiation intensity, or about a 5:1, about a 10:1 or about a 15:1 ratio of radiation intensity between target and background. In certain methods of the present disclosure, the radiation intensity of the target tissue is more intense than that of the background. In other embodiments, the present disclosure provides methods where the radiation intensity of the target tissue is less intense than that of the background. Generally, any difference in radiation intensity between the target tissue and the background that is sufficient to allow for identification and visualization of the target tissue is sufficient for use in the methods of the present disclosure. In some methods of the present disclosure, the compounds of the present disclosure are excreted from tissues of the body quickly to prevent prolonged exposure to the radiation of the radiolabeled compound administered to the patient. In a particular embodiment, the radionuclide tracer provided herein can be used on an outpatient basis. Typically, compounds of the present disclosure are eliminated from the body in less than about 24 hours. Images can be generated by virtue of differences in the spatial distribution of the imaging agents that accumulate at a site. The spatial distribution may be measured using any imaging apparatus suitable for the imaging agent, for example, a gamma camera, a PET apparatus, a SPECT apparatus, MRS, MRI, or optical imaging apparatus, and the like. The extent of accumulation of the imaging agent may be quantified using known methods for quantifying radioactive emissions. A particularly useful imaging approach employs more than one imaging agent to perform simultaneous studies. Alternatively, the imaging method may be carried out a plurality of times with increasing administered doses. The amount of imaging agent used for diagnostic purposes and the duration of the imaging study will depend upon the radionuclide used to label the agent, the body mass of the patient, the nature and severity of the condition being evaluated and treated, the nature of 11 \\4158-6725-4109 v1 779282.000028 therapeutic treatments which the patient has undergone, and on the idiosyncratic responses of the patient. Ultimately, the attending physician will decide the amount of imaging agent to administer to each individual patient and the duration of the imaging study. In certain embodiments, it is contemplated that composition for uses in methods disclosed herein comprises the (S)-1-(2-(6-nitropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N- (pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide in greater than 70 %, 80%, 90%, 95% or 98% enantiomeric excess. The structure of (S)-1-(2-(6-nitropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide is . In methods disclosed herein comprises the (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)- N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide in greater than 70 %, 80%, 90%, 95% 12 \\4158-6725-4109 v1 779282.000028 or 98% enantiomeric excess. The structure of (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide is . the subject, e.g., through a vein, and a scanner is used to make detailed images of areas inside the body over time where the radioactive material is taken up by the cells, tissue, fluids, or organs. For example, when imaging, the scans for tracking (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)- N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide are contemplated to show the uptake of this tracer in the blood, brain, spinal cord, a muscle, spleen, heart, lung, pancreas, small intestine, large intestine, liver, bone, or combinations thereof. In certain embodiments, this disclosure relates to imaging methods comprising a) administering a (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2- yl)-2,3-dihydro-1H-indene-5-sulfonamide tracer to a subject; and b) scanning the subject for the emission / positron-emissions. The methods typically further comprise the steps of detecting the emissions and creating an image of an area of the subject indicating or highlighting the location of the compound containing the radionuclide in the subject. In certain embodiments, the data associated with the emissions and image are recorded on a non-transitory computer readable medium. In certain embodiments, the area of the subject is the central nervous system, brain, spinal cord, lymph nodes, groin, axilla, neck, lungs, liver, kidney, pancreas, stomach, balder, intestines, circulatory system, breast, prostate, or gallbladder. 13 \\4158-6725-4109 v1 779282.000028 The tracer may be administered by any suitable technique known in the art, such as direct injection. Injection may be an intravenous (IV) injection. Administration may be general or local to the site of interest. The tracer may be used in conjunction with another probe, for example a fluorescent probe. The two (or more) probes may be administered together, separately, or sequentially. The tracer of the present disclosure may be used to diagnose, assess, or monitor the progression or treatment of a disease or condition reported herein, such as pain, epilepsy, seizures movement disorders, cognitive disorders, and neurodegenerative disorders. In certain embodiments, the neurodegenerative disease or cognitive disorder is, Alzheimer’s disease, ataxia, Huntington’s disease, Parkinson’s disease, Parkinsonism, motor neuron disease, multiple system atrophy, progressive supranuclear palsy multiple system atrophy, a neuromuscular disorder, or spasticity. The tracer of the present disclosure may be used to investigate the effects of a test compound. For example, (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N- (pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide may be administered together with a test compound, to evaluate the effect of the test compound be assayed in real time in vivo using a method in accordance with the present disclosure. The tracer of the present disclosure may be used with the test compound reported herein to diagnose, assess, or monitor the progression or treatment of a disease or condition, such as pain, epilepsy, seizures, movement disorders and neurodegenerative disorders. In certain embodiments, this disclosure relates to methods comprising: a) administering a composition comprising the (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N- (pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide tracer isotopically enriched with fluorine 18 to a subject; and scanning the subject for emissions from an area of the subject. In certain embodiments, methods further comprise the step of detecting and / or measuring the emissions and creating an image indicating or highlighting the location of the compound isotopically enriched with fluorine 18 in the subject. In certain embodiments, methods comprise the step of detecting, measuring, and / or quantifying the emission providing an emission quantity and optionally correlating the emission measurement / detection / quantity to a concentration of (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide in a tissue or other area. 14 \\4158-6725-4109 v1 779282.000028 In certain embodiments, methods further comprise the step of correlating a high, low, or abnormal measurement, quantity, or concentration of (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide existence of or diagnosis of a subject at risk of associated pain, epilepsy, seizures, movement disorders, central nervous system disease, or neurodegenerative disease. In certain embodiments, this disclosure relates to method of making a PET imaging agent, i.e., the (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2- yl)-2,3-dihydro-1H-indene-5-sulfonamide tracer, comprising contacting a precursor compound (S)-1-(2-(6-nitropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H- indene-5-sulfonamide with an isotopically enriched fluorine 18 negative ion producing the PET imaging tracer (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2- yl)-2,3-dihydro-1H-indene-5-sulfonamide. In certain embodiments, the enriched fluorine 18 negative ion is a fluorine 18 potassium salt bound to a cryptand. In certain embodiments, methods disclosed herein are used to detect, measure, quantify, assess, diagnose, or evaluate in a subject (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide concentrations in a subject suspected of having, being at risk of, or diagnosed with a pain disorder, epilepsy, seizure, movement disorder, cognitive disorder, or central nervous system disorder. In certain embodiments, this disclosure relates to methods of administering the (S)-1-(2- (6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H- indene-5-sulfonamide tracer in combination with pain associated drug or a test compound, epilepsy associated drug or a test compound, seizure associated drug or a test compound, movement disorders associated drug or a test compound, neurodegenerative associated drug or a test compound, cognitive disorder associated drug or a test compound, or central nervous system disorder associated drug or a test compound to a subject and imaging, detecting, measuring, or quantifying the PET signal in a sample, tissue, connective tissue, blood, bodily fluid, organ or portion / segment thereof, of the subject in order to evaluate the ability of a test compound and / or drug to bind voltage-gated sodium channel enriched tissue of the subject. 15 \\4158-6725-4109 v1 779282.000028 In certain embodiments, methods further comprise determining whether a subject is or would likely be responsive to a drug or test compound therapy. In certain embodiments, the drug is a pain reliever or a test compound. In certain embodiments, the subject has, is suspected of having, at risk of, or diagnosed with a pain disorder. In certain embodiments, the drug is acetaminophen, a nonsteroidal anti-inflammatory drug (NSAIDs), aspirin, naproxen, ibuprofen, or an opioid such as codeine, fentanyl, hydrocodone, meperidine, methadone, naloxone, or oxycodone. In certain embodiments, the drug is an epilepsy drug or a test compound, seizure associated drug or a test compound. In certain embodiments, the subject has, is suspected of having, at risk of, or diagnosed with a seizure. In certain embodiments, the drug is lacosamide, pregabalin, gabapentin, carbamazepine, oxcarbazepine, ezogabine, phenytoin, or vigabatrin. In certain embodiments, the drug is a movement disorders associated drug or a test compound. In certain embodiments, the subject has, is suspected of having, at risk of, or diagnosed with a movement disorder. In certain embodiments, the drug is levodopa, dopamine agonist, MAO-B antagonist, COMT-inhibitor, anticholinergic, amantadine, or antidepressants. In certain embodiments, the drug is a neurodegenerative disorder associated drug or a test compound. In certain embodiments, the subject has, is suspected of having, at risk of, or diagnosed with a neurodegenerative disorder. In certain embodiments, the drug is amantadine, apomorphine, donepezil, baclofen, dantrolene, carbidopa, or levodopa. In certain embodiments, the drug is a Mao-B inhibitor, safinamide, selegiline, or rasagiline. In certain embodiments, the drug is a COMT inhibitor such as entacapone, opicapone, and tolcapone. In certain embodiments, the drug is lecanemab, aducanumab, or gantenerumab. Lecanemab and aducanumab are therapeutic antibodies clinically approved for patients with mild cognitive impairment (MCI) or mild dementia due to Alzheimer's disease. In certain embodiments, if the imaging, detecting, measuring, or quantifying of the PET signal indicates the (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N- (pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide tracer binds to the voltage-gated sodium channel enriched tissue of the subject that is lower than a normal or reference value absent the test compound, then said imaging, detecting, measuring, or quantifying provides an indication that the test compound or targeted drug is binding or likely binding with sufficient affinity in the subject to be effective as a potential therapeutic agent. In certain embodiments, methods further 16 \\4158-6725-4109 v1 779282.000028 comprise the step of administering an effective amount of the test compound or targeted drug to a subject in need thereof. In certain embodiments, if the imaging, detecting, measuring, or quantifying of the PET signal indicates that the S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N- (pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide tracer binds to the cells or tissue of the subject is normal when compared to a reference value, then that is an indication that the test compound or pain-targeted drug is not binding or not binding with sufficient affinity to in the subject to be effective as a potential therapeutic agent. In certain embodiments, methods further comprise the step of recording the imaging, detecting, measuring, or quantifying data or diagnostic indications therefrom on a non-transitory computer readable medium. In certain embodiments, methods further comprise the step of reporting the imaging, detecting, measuring, or quantifying data or diagnostic indications therefrom to a medical professional. In certain embodiments, this disclosure relates to methods of diagnosing and treating a subject with a pain disorder, neurodegenerative disease, cognitive disorder or condition comprising administering an effective amount of (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide to a subject in need thereof; measuring18F emissions from the subject; comparing the18F brain emission to a normal or reference value; and diagnosing the subject with or at risk of a disease, or pain disorder, if the emission is lower or higher than normal; and treating the subject by administering to the subject an effective amount of a therapeutic agent directed to a disease or condition reported herein. In certain embodiments, this disclosure relates to a cell culture or growth medium comprising (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)- 2,3-dihydro-1H-indene-5-sulfonamide or salt thereof. In certain embodiments, this disclosure relates to evaluating or monitoring the effectiveness of a drug therapy or recombinant therapy comprising administering a drug for treating a disease or condition reported herein in combination with, or sometime after, the (S)-1- (2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H- indene-5-sulfonamide tracer, and thereafter imaging, detecting, measuring, or quantifying the tracer at a location in the subject. 17 \\4158-6725-4109 v1 779282.000028 In certain embodiments, the subject is a human subject. For example, the subject can be a human that is aged 2 years or older (e.g., 2, 12, or 16 years old, or older) or less than 2 years old. In certain embodiments, the subject is a human subject aged 18 years or older, and less than 65 years. In certain embodiments, the subject is a human subject that is 55 years old, or older. In some embodiments, the subject is a human subject that is 65 years old, or older. In certain embodiments, the subject is an infant, e.g., from one month to two years of age. In certain embodiments, the subject is a human subject such as a child, e.g., from two to twelve years of age. In certain embodiments, the subject is a human subject such as an adolescent, e.g., from twelve to sixteen years of age. In certain embodiments, the subject is a human subject sixteen years of age or older. Kits In certain embodiments, this disclosure relates to kits comprising a (S)-1-(2-(6- [18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene- 5-sulfonamide tracer and / or precursor compound, e.g., (S)-1-(2-(6-nitropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide and instructions for use. In certain embodiments, the instructions provide for the activity at the end of synthesis. In certain embodiments, the instructions provide for the half-life of the radionuclide. In certain embodiments, the instructions provide that injection should be used within limited time from the time of the end of synthesis. In certain embodiments, the container is a sealed container such as a septum capped vial. In certain embodiments, this disclosure relates to kits comprising the precursor (S)-1-(2- (6-nitropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5- sulfonamide and starting materials to make the radionuclide tracer (S)-1-(2-(6- [18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene- 5-sulfonamide, and / or a substance for preparing a radionuclide in a cyclotron. In certain embodiments, the kit comprises a container having water, H218O, and / or ethanol in water solution. In certain embodiments, the container is sealed from the atmosphere. In certain embodiments, kits comprise a solid support or filter. In certain embodiments, the filter may be used to purify a radionuclide tracer disclosed herein. 18 \\4158-6725-4109 v1 779282.000028 In certain embodiments, the tracer may be prepared at the location of the subject near the time the subject is exposed to an imaging device. Thus, in certain embodiments, the disclosure contemplates kits comprising the precursor compound (S)-1-(2-(6-nitropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide and a solid support. In some embodiments, the solid support is selected from the group of solid phase extraction resins or liquid chromatography resins, e.g., silica (oxide) based or non-silica (metal oxide or polymers) based particles optionally functionalized (e.g., by organosilanization) with alkyl chains for example C4, C8, C18, C30 or other functional groups, e.g., polar groups (amide, carbamate, and urea) embedded within alkyl chains or branched alkyl groups or polymeric packings. In some embodiments, the solid support is selected from the group consisting of solid phase extraction resins and liquid chromatography resins resulting from the copolymerization of divinylbenzene and / or styrene, or by the copolymerization with vinylpyrrolidone, vinylacetate, (methacryloyloxymethyl)naphtalene, 4,4′-bis(maleimido)diphenylmethane, p,p′-dihydroxy diphenylmethane diglycidyl methacrylic ester, p,p′-dihydroxydiphenylpropane diglycidyl methacrylic ester, 2-hydroxyethylmethacrylate (HEMA), 2,2-dimethylaminoethylmethacrylate (DMAEMA), ethylene dimethacrylate glycidyl methacrylate, N-vinyl carbazole, acrylonitrile, vinyl pyridine, N-methyl-N-vinyl acetamide, amino styrene, methylacrylate, ethylacrylate, methyl methacrylate, N-vinyl caprolactam, N-methyl-N-vinyl acetamide. In some embodiments, the solid support comprises or is functionalized with or preconditioned with: quaternary ammonium salts, e.g., tetraethylammonium carbonate, tetrabutylammonium carbonate; potassium carbonate cryptands such as [2.2.2] cryptand N(CH2CH2OCH2CH2OCH2CH2)3N, 1,4,10-trioxa-7,13-diaza-cyclopentadecane, 4,7,13,16,21,24- hexaoxa-1,10-diazabicyclo[8.8.8]hexacosane, 4,7,13,16,21-pentaoxa-1,10-diazabicyclo[8.8.5] tricosane, 4,7,13,18-tetraoxa-1,10-diazabicyclo[8.5.5] eicosane, 5,6-benzo-4,7,13,16,21,24- hexaoxa-1,10-diazabicyclo[8.8.8] hexacos-5-ene; crown ethers such as 4′-aminobenzo-15-crown-5, 4′-aminobenzo-15-crown-5, 19 \\4158-6725-4109 v1 779282.000028 4′-aminobenzo-15-crown-5 hydrochloride, 4′-aminobenzo-18-crown-6, a′-Aminodibenzo-18- crown-6, 2-aminomethyl-15-crown-5, 2-aminomethyl-15-crown-5, 2-aminomethyl-18-crown-6, 4′-amino-5′-nitrobenzo-15-crown-5, 4′-amino-5′-nitrobenzo-15-crown-5, 1-aza-12-crown-4, 1- aza-15-crown-5, 1-aza-15-crown-5, 1-aza-18-crown-6, 1-aza-18-crown-6, benzo-12-crown-4, 5,6-benzo-4,7,13,16,21,24-hexaoxa-1,10-diazabicyclo[8.8.8]hexacos-5-ene, 1-benzyl-1-aza-12- crown-4, bis[(benzo-15-crown-5)-15-ylmethyl]pimelate, 4′-bromobenzo-15-crown-5, 4-tert- butylbenzo-15-crown-5, 4-tert-butylcyclohexano-15-crown-5, 4′-carboxybenzo-15-crown-5; calixarenes such as 4-tert-butylcalix[4]arene, 4-tert-butylcalix[4]arene, 4-tert- butylcalix[4]arene, 4-tert-butylcalix[5]arene, 4-tert-butylcalix[6]arene, 4-tert-butylcalix[6]arene, 4-tert-butylcalix[6]arene, 4-tert-butylcalix[8]arene, 4-tert-butylcalix[8]arene, 4-tert- butylcalix[4]arene-tetraacetic acid tetraethyl ester, 4-tert-butylcalix[4]arene tetraacetic acid tetraethyl ester, 4-tert-butylcalix[4]arene-tetraacetic acid triethyl ester, calix[4]arene, calix[6]arene, calix[8]arene, 4-(chloromethyl)calix[4]arene, 4-isopropylcalix[4]arene, C- methylcalix[4]resorcinarene, C-methylcalix[4]resorcinarene, meso-octamethylcalix(4)pyrrole, 4- sulfocalix[4]arene, 4-sulfocalix[4]arene sodium salt, C-undecylcalix[4]resorcinarene monohydrate, C-undecylcalix[4]resorcinarene monohydrate; cyclodextrins such as α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, (2,6-di-O-)ethyl-β- cyclodextrin, 6-O-α-D-glucosyl-β-cyclodextrin, heptakis(6-O-t-butyldimethylsilyl-2,3-di-O- acetyl)-β-cyclodextrin, heptakis(2,6-di-O-methyl)-β-cyclodextrin, heptakis(2,3,6-tri-O-acetyl)-β- cyclodextrin, heptakis(2,3,6-tri-O-benzoyl)-β-cyclodextrin, hexakis (6-O-tertbutyl- dimethylsilyl)-α-cyclodextrin, hexakis (2,3,6-tri-O-acetyl)-α-cyclodextrin, hexakis (2,3,6-tri-O- methyl)-α-cyclodextrin, (2-hydroxyethyl)-β-cyclodextrin, 6-O-α-maltosyl-β-cyclodextrin hydrate, methyl-β-cyclodextrin, 6-monodeoxy-6-monoamino-β-cyclodextrin, octakis (6-O-t- butyldimethylsilyl)-γ-cyclodextrin, sulfopropyl-β-cyclodextrin, triacetyl-α-cyclodextrin, triacetyl-β-cyclodextrin; EDTA and derivatives such as ethylenediamine-N,N′-diacetic acid, 2-bis(2- aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid, trans-1,2-diaminocyclohexane-N,N,N′,N′- tetraacetic acid monohydrate, trans-1,2-diaminocyclohexane-N,N,N′,N′-tetraacetic acid monohydrate, 1,3-diamino-2-hydroxypropane-N,N,N′,N′-tetraacetic acid, 1,2-diaminopropane- N,N,N′,N′-tetraacetic acid, 1,3-diaminopropane-N,N,N′,N′-tetraacetic acid, 1,3-diamino-2- propanol-N,N,N′,N′-tetraacetic acid, diethylenetriamine-pentaacetic acid calcium trisodium salt 20 \\4158-6725-4109 v1 779282.000028 hydrate, N-(2-hydroxyethyl)ethylenediamine triacetic acid trisodium salt hydrate, N-(2- hydroxyethyl)ethylenediamine-N,N′,N′-triacetic acid; and / or polyethylene glycols (PEG), polyethylene oxides (PEO). Pharmaceutical compositions In certain embodiments, this disclosure relates to pharmaceutical compositions comprising (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)- 2,3-dihydro-1H-indene-5-sulfonamide or salt thereof or a precursor compound disclosed herein such as (S)-1-(2-(6-nitropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3- dihydro-1H-indene-5-sulfonamide or salt thereof, and a pharmaceutically acceptable excipient. In certain embodiments, the disclosure relates to a pharmaceutical composition comprising a compound as described herein including salts thereof and a pharmaceutically acceptable excipient, diluent, or carrier. In certain embodiments, the pharmaceutical composition is in the form of a powder, liquid, or aqueous buffered solution. In certain embodiments, the buffered solution is a citrate buffered solution, isotonic solution, sterile solution, pyrogen free solution, endotoxins and exotoxins free solution, lipopolysaccharide free solution, and / or bacterial free solution. Compounds disclosed herein, such as (S)-1-(2-(6-nitropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide or (S)-1-(2- (6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H- indene-5-sulfonamide may be in the form of pharmaceutically acceptable salts. Non-limiting examples of pharmaceutically acceptable acids for salt formation are hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, acetic acid, ascorbic acid, and citric acid, as well as other pharmaceutically acceptable acids known per se. Pharmaceutical compositions disclosed herein may be in the form of pharmaceutically acceptable salts. Non-limiting examples of pharmaceutically acceptable acids for salt formation are hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, acetic acid, ascorbic acid, and citric acid, as well as other pharmaceutically acceptable acids known per se. EXAMPLES Example 1. Synthetic preparations of compounds. 21 \\4158-6725-4109 v1 779282.000028 , BnSH (29.7 g, 239 mmol), K2CO3 (55.2 g, 399 mmol) in DMF (280 mL) was degassed and purged with N2 for three times, and then the mixture was stirred at 70 °C for 6 h under N2atmosphere. LC-MS showed desired compound was detected. The filtrate was diluted with ethyl acetate 300 mL and extracted with H2O 450 mL (150 mL × 3). The combined organic layers were washed with aqueous NaCl 450 mL (150 mL × 3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The crude product was triturated with MTBE at 25 °C for 30 min. Compound 2 (43.0 g, 169 mmol, 63% yield) was obtained as a yellow solid. 1H NMR: (400 MHz, CDCl3) δ 7.63 (d, J = 8.0 Hz, 1H), 7.29-7.42 (m, 5H), 7.22-7.29 (m, 2H), 4.25 (s, 2H), 2.98-3.14 (m, 2H), 2.58-2.72 (m, 2H). g, 185 mmol) in MeOH (450 mL) was degassed and purged with N2for three times, then the mixture was stirred at 70 °C for 12 h under N2atmosphere. LC-MS showed desired compound was detected. The reaction mixture was cool to 0 °C, and then filtered with MeOH 1000 mL at 0 °C. The filtrate was concentrated under reduced pressure to give a residue. Compound 4 (68.0 g, 160 mmol, 95% yield) was obtained as a yellow solid. 1H NMR: (400 MHz, DMSO-d6) δ 10.30 (s, 1H), 7.80 (d, J = 8.0 Hz, 2H), 7.19-7.42 (m, 10H), 4.28 (s, 2H), 2.91-2.99 (m, 2H), 2.67-2.75 (m, 2H), 2.37 (s, 3H). 22 \\4158-6725-4109 v1 779282.000028 170 mmol), Na2CO3(30.1 g, 283 mmol), cyclopentyl(diphenyl)phosphane;dichloromethane;dichloropalladium;iron (9.28 g, 11.3 mmol) in dioxane (360 mL) and H2O (60.0 mL) was degassed and purged with N2 for three times, then the mixture was stirred at 110 °C for 8 h under N2atmosphere. TLC (petroleum ether : ethyl acetate = 10 : 1）showed desired compound was detected. The reaction mixture was diluted with H2O (500 mL) and extracted with ethyl acetate 1000 mL (500 mL × 2). The combined organic layers were washed with aqueous NaCl 600 mL (300 mL × 2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether: ethyl acetate = 10 : 1). Compound 6 (28.0 g, 67.1 mmol, 59% yield) was obtained as a brown solid. 1H NMR: (400 MHz, CDCl3) δ 7.78 (s, 1H), 7.56-7.61 (m, 1H), 7.48-7.54 (m, 2H), 7.28- 7.32 (m, 4H), 7.22-7.27 (m, 2H), 7.07 (d, J = 8.0 Hz, 1H), 6.63 (t, J = 2.0 Hz, 1H), 4.15 (s, 2H), 3.56 (d, J = 1.6 Hz, 2H). , (4.48 g, 33.5 mmol) in AcOH (40.0 mL) and H2O (4.00 mL), then the mixture was stirred at 0 °C for 1 h under N2atmosphere. TLC (petroleum ether : ethyl acetate = 10 : 1) showed desired compound was detected. The reaction 23 \\4158-6725-4109 v1 779282.000028 mixture was diluted with H2O (20.0 mL) and extracted with DCM (60 mL, 30 mL × 2). The combined organic layers were washed with aqueous NaCl 100 mL (50.0 mL × 2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether : ethyl acetate = 10: 1). Compound 7 (3.60 g, 9.16 mmol, 95% yield) was obtained as a brown solid. mmol), TEA (3.71 g, 36.6 mmol,) in DCM (30.0 mL) at 0 °C, was stirred at 25 °C for 1h under N2atmosphere. LC-MS and TLC (petroleum ether : ethyl acetate = 10:1) showed desired compound was detected. The reaction mixture was diluted with H2O 50.0 mL and extracted with DCM 100 mL (50.0 mL × 2). The combined organic layers were washed with aqueous NaCl 100 mL (50.0 mL × 2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether : ethyl acetate = 10: 1). Compound 9 (2.90 g, 5.36 mmol, 59% yield) was obtained as a yellow solid. 1H NMR: (400 MHz, DMSO-d6) δ 8.23 (s, 1H), 8.08 (s, 1H), 7.93 (dd, J = 8.2, 1.6 Hz, 1H), 7.85-7.89 (m, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.22 (s, 1H), 5.07 (s, 1H), 3.84-3.89 (m, 2H). 24 \\4158-6725-4109 v1 779282.000028 purity) in ethyl acetate (40 mL) was degassed and purged with H2(40 psi) for three times, then the mixture was stirred at 60 °C for 24 h under H2 (40 psi) atmosphere. TLC (petroleum ether : ethyl acetate = 10 : 1) showed desired compound was detected. The reaction mixture was filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether : ethyl acetate = 10 : 1). Compound 10 (1.00 g, 1.84 mmol, 25% yield) was obtained as yellow oil. 1H NMR: (400 MHz, DMSO-d6) δ 7.92-8.07 (m, 2H), 7.81 (dd, J = 8.0, 1.8 Hz, 1H), 7.65-7.71 (m, 1H), 7.19-7.33 (m, 2H), 5.02 (t, J = 8.4 Hz, 1H), 3.02-3.23 (m, 2H), 2.67-2.75 (m, 1H), 2.12 (dq, J = 12.0, 8.4 Hz, 1H) , mmol) in THF (50 mL), was prepared. LiHMDS (1 M, 9.52 mL) was added in THF (50 mL) (degassed and purged with N2 for three times). The mixture was stirred at 0 °C for 1 h under N2 atmosphere. LC-MS and TLC (petroleum ether : ethyl acetate = 1 : 1) showed desired compound was detected. The reaction mixture was quenched by addition aqueous HCl (1 M, 40 mL), then extracted with ethyl acetate 100 mL (50 mL × 2). The combined organic layers were washed with aqueous NaCl 40 mL (20 mL × 2), dried over Na2SO4, filtered and concentrated under 25 \\4158-6725-4109 v1 779282.000028 reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether : ethyl acetate = 1 : 1). Compound 12 (1.35 g, 2.97 mmol, 69% yield) was obtained as a white solid. 1H NMR: (400 MHz, CDCl3) δ 8.66 (d, J = 5.2 Hz, 2H), 8.07 (s, 1H), 7.98 (d, J = 8.0 Hz, 1H), 7.70 (s, 1H), 7.42 (d, J = 8.4 Hz, 1H), 6.98-7.13 (m, 3H), 4.94 (t, J = 8.4 Hz, 1H), 2.99-3.20 (m, 2H), 2.66-2.82 (m, 1H), 1.97-2.11 (m, 1H). equiv.), XPhos Pd G3 (20 mol%) and XPhos (20 mol%) in dioxane and H2O (10 : 1) was degassed and purged with N2for three times, and then the mixture was stirred at 100 °C for 6 h under N2 atmosphere. LC-MS and TLC showed desired compound was detected. The reaction mixture was quenched by addition aqueous H2O (20 mL), then extracted with ethyl acetate 60 mL (30 mL × 2). The combined organic layers were washed with aqueous NaCl 40 mL (20.0 mL × 2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by column chromatography (SiO2, petroleum ether : ethyl acetate = 1 : 1). Compound 15, 1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)- 2,3-dihydro-1H-indene-5-sulfonamide, and 16, (S)-1-(2-(6-nitropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide, could be obtained as a yellow white solid respectively. 26 \\4158-6725-4109 v1 779282.000028 mm × 30 mm, 10 um). Mobile phase: [CO2-iPrOH (0.1% NH3·H2O)]; B%: 45%; isocratic elution mode. 1H NMR: (400 MHz, MeOD) δ 8.43 (d, J = 4.8 Hz, 2H), 8.26 (d, J = 2.0 Hz, 1H), 7.95-8.02 (m, 2H), 7.87 (br d, J = 8.0 Hz, 1H), 7.58-7.68 (m, 2H), 7.15-7.27 (m, 2H), 6.96-7.03 (m, 2H), 4.41 (br t, J = 8.8 Hz, 1H), 3.07-3.17 (m, 1H), 2.90-3.00 (m, 1H), 2.50-2.61 (m, 1H), 2.11 (dq, J = 12.8, 9.2 Hz, 1H). (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro- 1H-indene-5-sulfonamide: [18F]-(S)-15 27 \\4158-6725-4109 v1 779282.000028 (S)-16 was obtained by prep-SFC with REGIS (s,s) WHELK-O1TMcolumn (250 mm × 30 mm, 5 um). Mobile phase: [CO2-EtOH (0.1% NH3·H2O)]; B%: 60%; isocratic elution mode. 1H NMR: (400 MHz, MeOD) δ 8.68 (br s, 1H), 8.38-8.49 (m, 3H), 8.25 (br d, J = 7.6 Hz, 1H), 7.96 (br s, 1H), 7.87 (br d, J = 7.6 Hz, 1H), 7.68-7.77 (m, 2H), 7.30 (br d, J = 8.0 Hz, 1H), 6.96-7.08 (m, 2H), 4.38-4.47 (m, 1H), 3.08-3.17 (m, 1H), 2.95 (br d, J = 8.0 Hz, 1H), 2.58 (br d, J = 6.0 Hz, 1H), 2.10-2.20 (m, 1H). 28 \\4158-6725-4109 v1

Claims

1. 779282.000028 CLAIMS What is claimed is:

1. A compound (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N- (pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide, or salt thereof.

2. A pharmaceutical composition comprising the compound of claim 1 and a pharmaceutically acceptable excipient.

3. A compound (S)-1-(2-(6-nitropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2- yl)-2,3-dihydro-1H-indene-5-sulfonamide, or salt thereof.

4. A kit comprising a compound as in claim 1 or claim 3.

5. The kit of claim 4 further comprising potassium bound to a cryptand.

6. A method of making a compound of claim 1 comprising contacting a compound comprising (S)-1-(2-(6-nitropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide with an isotopically enriched fluorine 18 negative ion producing the compound(S)-1-(2-(6- [18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene- 5-sulfonamide.

7. The method of claim 6 wherein the enriched fluorine 18 negative ion is a fluorine 18 potassium salt bound to a cryptand.

8. A method comprising: a) administering a composition comprising the compound (S)-1-(2-(6-[18F]fluoropyridin- 3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide or salt thereof, isotopically enriched with fluorine 18 to a subject; and b) scanning the subject for emissions from an area of the subject. 29 \\4158-6725-4109 v1779282.000028 9. The method of claim 8, wherein the emissions are from or on the exterior or inside a nerve.

10. The method of claim 8 or claim 9, further comprising a step of detecting the emissions and creating an image indicating or highlighting the location of the compound isotopically enriched with fluorine 18 in the subject.

11. The method of any one of claims 8-10, further comprising the step of quantifying the emission providing an emission quantity and recording the emission quantity on non-transitory computer readable media.

12. The method of claim 11 further comprising correlating the emission quantity to concentration of (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4-(trifluoromethyl)phenyl)-N-(pyrimidin- 2-yl)-2,3-dihydro-1H-indene-5-sulfonamide in the area of the subject.

13. The method of claim 12 further comprising reporting the emission quantity to a medical professional.

14. A growth medium comprising (S)-1-(2-(6-[18F]fluoropyridin-3-yl)-4- (trifluoromethyl)phenyl)-N-(pyrimidin-2-yl)-2,3-dihydro-1H-indene-5-sulfonamide or salt thereof.

15. The growth medium of claim 14, comprising a nerve cell. 30 \\4158-6725-4109 v1