Protein aggregation diagnostics

Abstract

The invention relates generally to the diagnosis and monitoring of diseases associated with misfolded proteins.

Description

Atty. Docket: UCSF-849WOPROTEIN AGGREGATION DIAGNOSTICSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] Pursuant to 35 U. S. C. § 119(e), this application claims priority to the filing dates of United States Provisional Patent Application Serial Nos. 63 / 738,377 filed December 23, 2024, and 63 / 771,570 filed March 13, 2025, the disclosure of each of which is herein incorporated by reference in its entirety.FIELD OF THE INVENTION

[0002] The invention relates generally to the diagnosis and monitoring of diseases associated with protein aggregates.BACKGROUND OF THE INVENTION

[0003] Protein aggregation diseases are characterized by the formation of proteins that adopt disease-specific conformations and propagate by converting additional molecules of the same protein to the pathologic conformation and accumulate in the patient.

[0004] Unexpectedly, the inventors have discovered methods for diagnosing and monitoring protein aggregation diseases. This, among other inventions, is provided in this disclosure.GENERAL INFORMATION

[0005] Before the present methods and uses are described, it is to be understood that this invention is not limited to particular steps, devices and compounds described, as such may, of course, vary. 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, since the scope of the present invention will be limited only by the appended claims.

[0006] Where a range of values is provided, it is understood that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically disclosed. Each smaller range between any stated value or intervening value in a stated range and any other stated or intervening value in that stated range is encompassed within the invention. The upper and lower limits of theseAtty. Docket: UCSF-849WOsmaller ranges may independently be included or excluded in the range, and each range where either, neither or both limits are included in the smaller ranges is also encompassed within the invention, subject to any specifically excluded limit in the stated range. Where the stated range includes one or both of the limits, ranges excluding either or both of those included limits are also included in the invention.

[0007] 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 invention belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, some potential and preferred methods and materials are now described. All publications mentioned herein are incorporated herein by reference to disclose and describe the methods and / or materials in connection with which the publications are cited. It is understood that the present disclosure supersedes any disclosure of an incorporated publication to the extent there is a contradiction.

[0008] It must be noted that as used herein and in the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a scan" includes a plurality of such scans and reference to "the Biomarker of Response" includes reference to one or more such Biomarkers of Response and equivalents thereof known to those skilled in the art, and so forth.

[0009] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.

[0010] All patents and publications, including all sequences disclosed within such patents and publications, referred to herein are expressly incorporated by reference.BRIEF SUMMARY OF THE INVENTION

[0011] In one aspect, the invention provides a method of measuring protein aggregates in a patient by a technique, comprising: a) administering a first compound and a second compound to the patient, wherein the first compound is not detectable (or essentially not detectable) by theAtty. Docket: UCSF-849WOtechnique, and wherein the second compound is detectable by the technique; b) allowing the first compound and the second compound to bind the protein aggregates; and c) detecting the binding of the second compound to the protein aggregates thereby measuring the protein aggregates in the patient. In another aspect, the invention provides a method of measuring protein aggregates in a patient by a technique, comprising: a) administering a first compound not detectable (or essentially not detectable) by the technique to the patient; b) allowing the first compound to bind the protein aggregates; c) administering a second compound detectable by the technique to the patient; d) allowing the second compound to bind the protein aggregates; and e) detecting the binding of the second compound to the protein aggregates, thereby measuring the protein aggregates in the patient. In an exemplary embodiment, the binding of the first compound to the protein aggregates enhances the binding of the second compound to the protein aggregates. In an exemplary embodiment, the binding of the first compound to the protein aggregates increases the ability of the second compound to bind to the protein aggregates. In an exemplary embodiment, the first compound is in contact with the second compound in the protein aggregates.

[0012] The publications discussed herein are provided solely for their disclosure prior to the filing date of the present application. Nothing herein is to be construed as an admission that the present invention is not entitled to antedate such publication by virtue of prior invention.Further, the dates of publication provided may be different from the actual publication dates which may need to be independently confirmed.

[0013] All patents and publications, including all sequences disclosed within such patents and publicationsBRIEF DESCRIPTION OF THE DRAWINGS

[0014] FIG 1 shows Ml and control (HEK) cells at various concentrations of first Compound 24 co-dosed with 1 pCi of PET agent second 18F-Compound 24.

[0015] FIG 2 shows Ml and control (HEK) cells at various concentrations of first Compound 499 co-dosed with 1 pCi of PET agent second 18F-Compound 24.

[0016] FIG 3 shows A8 and control (HEK) cells at various concentrations of first Compound 499 co-dosed with 1 pCi of PET agent second 18F-Compound 24.Atty. Docket: UCSF-849WO

[0017] FIG 4 shows Ml and control mouse brain homogenate at various concentrations of first Compound 499 co-dosed with 1 pCi of PET agent second18F-Compound 24.

[0018] FIG 5 shows patient brain homogenate at various concentrations of first Compound 499 co-dosed with 1 pCi of PET agent second18F-Compound 24.DETAILED DESCRIPTION OF THE INVENTIONI. Definitions

[0019] The symbol, whether utilized as a bond or displayed perpendicular to a bond, indicates the point at which the displayed moiety is attached to the remainder of the compound.

[0020] As used herein, the term “alkyl” by itself or as part of another substituent refers to a saturated branched or straight-chain monovalent hydrocarbon radical derived by the removal of one hydrogen atom from a single carbon atom of a parent alkane. Typical alkyl groups include, but are not limited to, methyl; ethyl, propyls such as propan- 1-yl or propan-2-yl; and butyls such as butan-l-yl, butan-2-yl, 2-methyl-propan-l-yl or 2-methyl-propan-2-yl. In some embodiments, an alkyl group comprises from 1 to 20 carbon atoms. In other embodiments, an alkyl group comprises from 1 to 10 carbon atoms. In still other embodiments, an alkyl group comprises from 1 to 6 carbon atoms, such as from 1 to 4 carbon atoms, such as from 1 to 3 carbon atoms.

[0021] " Alkanyl" by itself or as part of another substituent refers to a saturated branched, straight-chain or cyclic alkyl radical derived by the removal of one hydrogen atom from a single carbon atom of an alkane. Typical alkanyl groups include, but are not limited to, methanyl; ethanyl; propanyls such as propan-l-yl, propan-2-yl (isopropyl), cyclopropan-l-yl, etc.; butanyls such as butan-l-yl, butan-2-yl (sec-butyl), 2-methyl-propan-l-yl (isobutyl), 2-methyl-propan-2-yl (t-butyl), cyclobutan-l-yl, etc.; and the like.

[0022] " Alkylene" refers to a branched or unbranched saturated hydrocarbon chain, usually having from 1 to 20 carbon atoms, more usually 1 to 10 carbon atoms and even more usually 1 to 6 carbon atoms, such as from 1 to 4 carbon atoms, such as from 1 to 3 carbon atoms. This term is exemplified by groups such as methylene (-CH2-), ethylene (-CH2CH2-), the propylene isomers (e.g., -CH2CH2CH2- and -CH(CH3)CH2-) and the like.

[0023] " Alkenyl" by itself or as part of another substituent refers to an unsaturated branched, straight-chain or cyclic alkyl radical having at least one carbon-carbon double bond derived byAtty. Docket: UCSF-849WOthe removal of one hydrogen atom from a single carbon atom of an alkene. The group may be in either the cis or trans conformation about the double bond(s). Typical alkenyl groups include, but are not limited to, ethenyl; propenyls such as prop-l-en-l-yl, prop-l-en-2-yl, prop-2-en-l-yl (allyl), prop-2-en-2-yl, cycloprop- 1-en-l-yl; cycloprop-2-en-l-yl; butenyls such as but-l-en-l-yl, but-l-en-2-yl, 2-methyl-prop- 1-en-l-yl, but-2-en-l-yl, but-2-en-l-yl, but-2-en-2-yl, buta-1,3-dien-l-yl, buta-l,3-dien-2-yl, cyclobut- 1-en-l-yl, cyclobut-l-en-3-yl, cyclobuta-1.3-dien-l-yl, etc.; and the like.

[0024] " Alkynyl" by itself or as part of another substituent refers to an unsaturated branched, straight-chain or cyclic alkyl radical having at least one carbon-carbon triple bond derived by the removal of one hydrogen atom from a single carbon atom of an alkyne. Typical alkynyl groups include, but are not limited to, ethynyl; propynyls such as prop-l-yn-l-yl, prop-2-yn-l-yl, etc.; butynyls such as but-l-yn-l-yl, but-l-yn-3-yl. but-3-yn-l-yl, etc.; and the like.

[0025] " Acyl" by itself or as part of another substituent refers to a radical -C(O)R30, where R30is hydrogen, alkyl, cycloalkyl, heterocycloalkyl, aryl, arylalkyl, heteroalkyl, heteroaryl, heteroarylalkyl as defined herein and substituted versions thereof. Representative examples include, but are not limited to formyl, acetyl, cyclohexylcarbonyl, cyclohexylmethylcarbonyl, benzoyl, benzylcarbonyl, piperonyl, propionyl, succinyl, and malonyl, and the like.

[0026] The term "aminoacyl" refers to the group -C(O)NR21R22, wherein R21and R22independently are selected from the group consisting of hydrogen, alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, substituted aryl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic and where R21and R22are optionally joined together with the nitrogen bound thereto to form a heterocyclic or substituted heterocyclic group, and wherein alkyl, substituted alkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, cycloalkyl, substituted cycloalkyl, cycloalkenyl, substituted cycloalkenyl, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocyclic, and substituted heterocyclic are as defined herein.

[0027] " Alkoxy" by itself or as part of another substituent refers to a radical -OR31where R31represents an alkyl group as defined herein. Representative examples include, but are not limited to, methoxy, ethoxy, propoxy, butoxy, and the like.Atty. Docket: UCSF-849WO

[0028] " Cycloalkoxy" by itself or as part of another substituent refers to a radical -OR31where R31represents a cycloalkyl group as defined herein. Representative examples include, but are not limited to, cyclopropoxy, cyclobutoxy, cyclohexyloxy and the like.

[0029] " Alkoxycarbonyl" by itself or as part of another substituent refers to a radical -C(O)OR31where R31represents an alkyl or cycloalkyl group as defined herein. Representative examples include, but are not limited to, methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, butoxycarbonyl, cyclohexyloxycarbonyl and the like.

[0030] " Aryl" by itself or as part of another substituent refers to a monovalent aromatic hydrocarbon radical derived by the removal of one hydrogen atom from a single carbon atom of an aromatic ring system. Typical aryl groups include, but are not limited to, groups derived from aceanthrylene, acenaphthylene, acephen anthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, hexacene, hexaphene, hexalene, as-indacene, s-indacene, indane, indene, naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, pyranthrene, rubicene, triphenylene, trinaphthalene and the like. In certain embodiments, an aryl group comprises from 6 to 20 carbon atoms. In certain embodiments, an aryl group comprises from 6 to 12 carbon atoms. Examples of an aryl group are phenyl and naphthyl.

[0031] " Arylalkyl" by itself or as part of another substituent refers to an acyclic alkyl radical in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp3carbon atom, is replaced with an aryl group. Typical arylalkyl groups include, but are not limited to, benzyl, 2-phenylethan-l-yl, 2-phenylethen-l-yl, naphthylmethyl, 2-naphthylethan-l-yl, 2-naphthylethen-l-yl, naphthobenzyl, 2-naphthophenylethan-l-yl and the like. Where specific alkyl moieties are intended, the nomenclature arylalkanyl, arylalkenyl and / or arylalkynyl is used. In certain embodiments, an arylalkyl group is (C7-C30) arylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the arylalkyl group is (C1-C10) and the aryl moiety is (C6-C20). In certain embodiments, an arylalkyl group is (C7-C20) arylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the arylalkyl group is (Ci-Cs) and the aryl moiety is (C6-C12).

[0032] " Arylaryl" by itself or as part of another substituent, refers to a monovalent hydrocarbon group derived by the removal of one hydrogen atom from a single carbon atom of a ring system in which two or more identical or non-identical aromatic ring systems are joined directly togetherAtty. Docket: UCSF-849WOby a single bond, where the number of such direct ring junctions is one less than the number of aromatic ring systems involved. Typical arylaryl groups include, but are not limited to, biphenyl, triphenyl, phenyl-napthyl, binaphthyl, biphenyl-napthyl, and the like. When the number of carbon atoms in an arylaryl group are specified, the numbers refer to the carbon atoms comprising each aromatic ring. For example, (C5-C14) arylaryl is an arylaryl group in which each aromatic ring comprises from 5 to 14 carbons, e.g., biphenyl, triphenyl, binaphthyl, phenylnapthyl, etc. In certain embodiments, each aromatic ring system of an arylaryl group is independently a (C5-C14) aromatic. In certain embodiments, each aromatic ring system of an arylaryl group is independently a (C5-C10) aromatic. In certain embodiments, each aromatic ring system is identical, e.g., biphenyl, triphenyl, binaphthyl, trinaphthyl, etc.

[0033] " Cycloalkyl" by itself or as part of another substituent refers to a saturated or unsaturated cyclic alkyl radical derived by the removal of one hydrogen atom from a single carbon atom of the parent. Where a specific level of saturation is intended, the nomenclature "cycloalkanyl" or "cycloalkenyl" is used. Typical cycloalkyl groups include, but are not limited to, groups derived from cyclopropane, cyclobutane, cyclopentane, cyclohexane and the like. In certain embodiments, the cycloalkyl group is (C3-C10) cycloalkyl. In certain embodiments, the cycloalkyl group is (C3-C6) cycloalkyl.

[0034] " Heterocycloalkyl" or "heterocyclyl" by itself or as part of another substituent, refers to a saturated or unsaturated cyclic alkyl radical in which one or more carbon atoms (and any associated hydrogen atoms) are independently replaced with the same or different heteroatom. Typical heteroatoms to replace the carbon atom(s) include, but are not limited to, N. P, O. S, Si, etc. Where a specific level of saturation is intended, the nomenclature " heterocyclo alkanyl" or "heterocyclo alkenyl" is used. Typical heterocycloalkyl groups include, but are not limited to, groups derived from epoxides, azirines, thiiranes. imidazolidine, morpholine, piperazine, piperidine, pyrazolidine, pyrrolidine, quinuclidine and the like.

[0035] " Heteroalkyl, Heteroalkanyl, Heteroalkenyl and Heteroalkynyl" by themselves or as part of another substituent refer to alkyl, alkanyl, alkenyl and alkynyl groups, respectively, in which one or more of the carbon atoms (and any associated hydrogen atoms) are independently replaced with the same or different heteroatomic groups. Typical heteroatomic groups which can be included in these groups include, but are not limited to, -O-, -S-, -S-S-, -O-S-. -NR37R38-, =N-Atty. Docket: UCSF-849WON=, -N=N-, -N=N-NR39R40, -PR41-, -P(0)2-, -POR42-, -O-P(O)2-, -S-O-, -S-(O)-, -SO2-, -SnR43R44- and the like, where R37, R38, R39, R40, R41, R42, R43and R44are independently hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, arylalkyl, substituted arylalkyl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, heteroalkyl, substituted heteroalkyl, heteroaryl, substituted heteroaryl, heteroarylalkyl or substituted heteroarylalkyl.

[0036] " Heteroaryl" by itself or as part of another substituent, refers to a monovalent heteroaromatic radical derived by the removal of one hydrogen atom from a single atom of a heteroaromatic ring system. Typical heteroaryl groups include, but are not limited to, groups derived from acridine, arsindole, carbazole, [B-carboline, chromane, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole, pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene, benzodioxole and the like. In certain embodiments, the heteroaryl group is from 5-20 membered heteroaryl. In certain embodiments, the heteroaryl group is from 5-10 membered heteroaryl. In certain embodiments, heteroaryl groups are those derived from thiophene, pyrrole, benzothiophene, benzofuran, indole, pyridine, quinoline, imidazole, oxazole and pyrazine.

[0037] " Heteroarylalkyl" by itself or as part of another substituent, refers to an acyclic alkyl radical in which one of the hydrogen atoms bonded to a carbon atom, typically a terminal or sp3carbon atom, is replaced with a heteroaryl group. Where specific alkyl moieties are intended, the nomenclature heteroarylalkanyl, heteroarylalkenyl and / or heterorylalkynyl is used. In certain embodiments, the hetero arylalkyl group is a 6-30 membered heteroarylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the hetero arylalkyl is 1-10 membered and the heteroaryl moiety is a 5-20-membered heteroaryl. In certain embodiments, the heteroarylalkyl group is 6-20 membered heteroarylalkyl, e.g., the alkanyl, alkenyl or alkynyl moiety of the heteroarylalkyl is 1-8 membered and the heteroaryl moiety is a 5-12-membered heteroaryl.

[0038] " Aromatic Ring System" by itself or as part of another substituent, refers to an unsaturated cyclic or polycyclic ring system having a conjugated % electron system. SpecificallyAtty. Docket: UCSF-849WOincluded within the definition of "aromatic ring system" are fused ring systems in which one or more of the rings are aromatic and one or more of the rings are saturated or unsaturated, such as, for example, fluorene, indane, indene, phenalene, etc. Typical aromatic ring systems include, but are not limited to, aceanthrylene, acenaphthylene, acephenanthrylene, anthracene, azulene, benzene, chrysene, coronene, fluoranthene, fluorene, hexacene, hexaphene, hexalene, as-indacene. s-indacene, indane, indene, naphthalene, octacene, octaphene, octalene, ovalene, penta-2,4-diene, pentacene, pentalene, pentaphene, perylene, phenalene, phenanthrene, picene, pleiadene, pyrene, pyranthrene, rubicene, triphenylene, trinaphthalene and the like.

[0039] " Heteroaromatic Ring System" by itself or as part of another substituent, refers to an aromatic ring system in which one or more carbon atoms (and any associated hydrogen atoms) are independently replaced with the same or different heteroatom. Typical heteroatoms to replace the carbon atoms include, but are not limited to. N, P, O, S, Si, etc. Specifically included within the definition of "heteroaromatic ring systems" are fused ring systems in which one or more of the rings are aromatic and one or more of the rings are saturated or unsaturated, such as, for example, arsindole, benzodioxan, benzofuran, chromane, chromene, indole, indoline, xanthene, etc. Typical heteroaromatic ring systems include, but are not limited to, arsindole, carbazole, 0-carboline, chromane, chromene, cinnoline, furan, imidazole, indazole, indole, indoline, indolizine, isobenzofuran, isochromene, isoindole, isoindoline, isoquinoline, isothiazole, isoxazole, naphthyridine, oxadiazole, oxazole, perimidine, phenanthridine, phenanthroline, phenazine, phthalazine, pteridine, purine, pyran, pyrazine, pyrazole. pyridazine, pyridine, pyrimidine, pyrrole, pyrrolizine, quinazoline, quinoline, quinolizine, quinoxaline, tetrazole, thiadiazole, thiazole, thiophene, triazole, xanthene and the like.

[0040] “Substituted” refers to a group in which one or more hydrogen atoms are independently replaced with the same or different substituent(s). Typical substituents include, but are not limited to, alkylenedioxy (such as methylenedioxy), -M, -R60, -O’, =0, -OR60, -SR60, -S’, -S, -NR60R61, =NR60, -CF3, -CN, -OCN, -SCN, -NO, -NO2, =N2, -N3, -S(O)2O’, -S(O)2OH, -S(O)2R60, -OS(O)2O’, -OS(O)2R60, -P(O)(O’)2, -P(O)(OR60)(O ), -OP(O)(OR60)(OR61), -C(O)R60, -C(S)R60, -C(O)OR60, -C(O)NR60R61, -C(O)O’, -C(S)OR60, -NR62C(O)NR60R61, -NR62C(S)NR60R61, -NR62C(NR63)NR60R61and -C(NR62)NR60R61where M is halogen: R60, R61, R62and R63are independently hydrogen, alkyl, substituted alkyl, alkoxy, substituted alkoxy, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl,Atty. Docket: UCSF-849WOsubstituted aryl, heteroaryl or substituted heteroaryl, or optionally R60and R61together with the nitrogen atom to which they are bonded form a heterocycloalkyl or substituted heterocycloalkyl ring; and R64and R65are independently hydrogen, alkyl, substituted alkyl, aryl, cycloalkyl, substituted cycloalkyl, heterocycloalkyl, substituted heterocycloalkyl, aryl, substituted aryl, heteroaryl or substituted heteroaryl, or optionally R64and R65together with the nitrogen atom to which they are bonded form a heterocycloalkyl or substituted heterocycloalkyl ring. In certain embodiments, substituents include -M, -R60, =0, -OR60, -SR60, -S’, =S, -NR60R61, =R60, -CF3, -CN, -OCN, -SCN, -NO, -N02, =N2, -N3. -S(O)2R60. -0S(0)20’, -OS(O)2R60, -P(0)(0’)2, -P(O)(OR60)(O ), -OP(O)(OR60)(OR61), -C(O)R60, -C(S)R60, -C(O)OR60, -C(O)NR60R61, -C(0)0-, -NR62C(O)NR60R61. In certain embodiments, substituents include -M, -R60, =0, -OR60, -SR60, -NR60R61, -CF3. -CN. -N02, -S(O)2R60, -P(O)(OR60)(O ), -OP(O)(OR60)(OR61), -C(O)R60, -C(O)OR60, -C(O)NR60R61, -C(0)0. In certain embodiments, substituents include -M, -R60, =0, -OR60, -SR60, -NR60R61, -CF3, -CN, -N02, -S(O)2R60, -OP(O)(OR60)(OR61), -C(O)R60, -C(O)OR60, -C(0)0. where R60, R61and R62are as defined above. For example, a substituted group may bear a methylenedioxy substituent or one, two, or three substituents selected from a halogen atom, a (Ci-4)alkyl group and a (Ci-4)alkoxy group.

[0041] “Amino" refers to the group -NRXRYwherein Rxand RYare each independently H or a non-hydrogen substituent. Exemplary non-hydrogen substituents include alkyl groups (e.g. methyl, ethyl, and isopropyl).

[0042] “Ether” refers to a diradical group of formula -0-. For instance, if the ether group is connected to an alkyl group, then the overall group is an alkoxy group (e.g. -OCH3or methoxy). If the ether is connected to a carbonyl group, then the overall group is an ester group of formula -0C(0)-.

[0043] “Halo” and “halogen” refer to the chloro, bromo, fluoro, and iodo groups.

[0044] “Nitro” refers to the group of formula -NO2.

[0045] The terms "patient," "subject." and "human subject" are used interchangeably herein.

[0046] As to any of the groups disclosed herein which contain one or more substituents, it is understood, of course, that such groups do not contain any substitution or substitution patternsAtty. Docket: UCSF-849WOwhich are sterically impractical and / or synthetically non-feasible. Tn addition, the subject compounds include all stereochemical isomers arising from the substitution of these compounds.

[0047] In certain embodiments, a substituent may contribute to optical isomerism and / or stereo isomerism of a compound. Salts, solvates, hydrates, and prodrug forms of a compound are also of interest. All such forms are embraced by the present disclosure. Thus, the compounds described herein include salts, solvates, hydrates, prodrug and isomer forms thereof, including the pharmaceutically acceptable salts, solvates, hydrates, prodrugs and isomers thereof. In certain embodiments, a compound may be metabolized into a pharmaceutically active derivative.77. Introduction

[0048] The invention provides methods for detecting and / or measuring protein aggregates in a patient by a technique.777. Methods

[0049] In one aspect, the invention provides a method of measuring protein aggregates in a patient by a technique, comprising: a) administering a first compound and a second compound to the patient, wherein the first compound is not detectable (or essentially not detectable) by the technique, and wherein the second compound is detectable by the technique; b) allowing the first compound and the second compound to bind the protein aggregates; and c) detecting the binding of the second compound to the protein aggregates, thereby measuring the protein aggregates in the patient.

[0050] In another aspect, the invention provides a method of measuring protein aggregates in a patient by a technique, comprising: a) administering a first compound not detectable (or essentially not detectable) by the technique to the patient; b) allowing the first compound to bind the protein aggregates; c) administering a second compound detectable by the technique to the patient; d) allowing the second compound to bind the protein aggregates; and e) detecting the binding of the second compound to the protein aggregates, thereby measuring the protein aggregates in the patient.

[0051] In another aspect, the invention provides a method of measuring protein aggregates in a patient by a technique, comprising: a) administering a second compound detectable by the technique to the patient; b) allowing the second compound to bind the protein aggregates; c)Atty. Docket: UCSF-849WOadministering a first compound not detectable (or essentially not detectable) by the technique to the patient; d) allowing the first compound to bind the protein aggregates; and e) detecting the binding of the second compound to the protein aggregates, thereby measuring the protein aggregates in the patient.Illa. Second Compound

[0052] The second compound is detectable and / or measurable by a technique described herein. In an exemplary embodiment, the technique is positron emission tomography (PET), single photon emission computed tomography (SPECT), or autoradiography. In an exemplary embodiment, the second compound comprises one or more isotopically labeled atoms. In an exemplary embodiment, the second compound comprises one or more radiolabeled atoms. In an exemplary embodiment, the second compound is part of a complex, and the complex comprises one or more isotopically labeled atoms. In an exemplary embodiment, the second compound is part of a complex, and the complex comprises one or more radiolabeled atoms.IIIa1. PET

[0053] In an exemplary embodiment, the second compound comprises one or more radiolabeled atoms detectable and / or measurable by positron emission tomography (PET). In an exemplary embodiment, the second compound is part of a complex, and the complex comprises one or more radiolabeled atoms detectable and / or measurable by positron emission tomography (PET). In an exemplary embodiment, the radiolabeled atoms detectable and / or measurable by positron emission tomography (PET) are selected from the group consisting of11C,13N,15O,18F,52Mn,55Co,64Cu,68Ga,82Rb,89Zr. In an exemplary embodiment, the radiolabeled atoms detectable and / or measurable by positron emission tomography (PET) is11C,13N, or15O. In an exemplary embodiment, the radiolabeled atoms detectable and / or measurable by positron emission tomography (PET) is18F.

[0054] In an exemplary embodiment, the second compound binds to beta-amyloid protein aggregates. In an exemplary embodiment, the second compound is described in Klunk et al. Ann Neurol 2004; 55:306-319, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which isAtty. Docket: UCSF-849WO(also [11C]PiB or | " C (Pittsburgh compound B). In an exemplary embodiment, the second compound is described in US 2013 / 012718, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which issNHN CH3 (also [18F]Flutemetamol). In an exemplary embodiment, the second compound is described in Applied Radiation and Isotopes Volume 68, Issue12, December 2010, Pages 2293-2297, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a, C\HN0structure whichis (also [18F]Florbetapir (AV-45)). In an exemplary embodiment, the second compound is described in Jure his et al. J Neurochem.2010; 114: 784-794, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which isQ CH / 'NH(also [18F]NAV4694 (AZD4694)). In an exemplary embodiment, the second compound is described in Rowe et al. Lancet Neurol. 2008;7:129-135, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which isHN(also [18F]Florbetaben (AV-1; BAY94-9172)). In an exemplary embodiment, the second compound is described in Wang et al. Journal of Nuclear Medicine May 2006, 47 (suppl 1) 217P, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compoundAtty. Docket: UCSF-849WO18Fhas a structure which isNH2 (also [18F]FBA). In an exemplary embodiment,the second compound has a structure whichis (also [18F]FBM). In an exemplary embodiment, the second compound is described in PCT Pub No W02006083378, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which isNC CN18FI (also [18F]FDDNP). In an exemplary embodiment, the second compound is described in He-Huaxue yu Fangshe Idw ud Journal of Nuclear and Radiochemistry 35(l):40-45, D01:10.7538 / hhx.2013.35.01.0040, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, theN IIN |VsNH3C^ec nd cS s o ompound has a structure which is O (also [18F]W372). In an exemplary embodiment, the second compound is described in Nuclear Medicine and Biology, Volume 38. Issue 8, November 2011. Pages 1193-1203, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplaryOembodiment, the second compound has a structure whichis (also [18F]MK3328). In an exemplary embodiment, the second compound is described in Newberg et al, Journal of Nuclear Medicine, May 2006, 47(5), 748-754, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, theAtty. Docket: UCSF-849WOsecond compound has a structure which is123i [123I]IMPY).

[0055] In an exemplary embodiment, the second compound binds to tau protein aggregates. In an exemplary embodiment, the second compound binds to a-synuclein protein aggregates. In an exemplary embodiment, the second compound is described in Neuron, 2013 September 18; 79(6);doi:10.1016 / j.neuron.2013.07.037, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound SN\ H / > — N / / 11has a structure which isCH3 (also [11C]PBB3). In an exemplary embodiment, the second compound is described in JP2007223952, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which iss.0 Q ' II (also [11C]BF-227). In an exemplary embodiment, the second compound has a structure which isSQ ' IN (also [18F]BF-227). In an exemplary embodiment, the second compound has a structure which isS^N O. Q T I V'N (also [18F]THK-525). In an exemplaryAtty. Docket: UCSF-849WOembodiment, the second compound has a structure which is(also [18F]THK-702). In an exemplary embodiment, the second compound has a structure which is(also [18F]THK-727). In an exemplary embodiment, the second compound has a structure which is(also [18F]FACT). In an exemplary embodiment, the second compound is described in Nuclear Medicine and Biology Volume 46, March 2017, Pages 50-53, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structureCH3(also [18F]THK5117). In an exemplary embodiment, the second compound is described in J Nucl Med. 2016 Feb;57(2):208- 14. doi: 10.2967 / jnumed.l 15.164848. Epub 2015 Nov 5. C21, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the secondAtty. Docket: UCSF-849WOCH3(also [18F]THK5351 (S-enantiomer)). In an exemplary embodiment, the second compound has a(also [11C]THK5351 (S-enantiomer)). In an exemplary embodiment, the second compound is described in Eur J Nucl Med Mol Imaging (2016) 43:1686-1699 DOI 10.1007 / s00259-016-3363-z, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound is described in US Pat Pub No 2016 / 244411, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which isCH3CH3 (also [18F]THK5105). In an exemplary embodiment, the second compound has a structure which isembodiment, the second compound is described in CN103242229 A, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, theAtty. Docket: UCSF-849WO18F.second compound has a structure whichisNH2 (also [18F]THK523). In an exemplary embodiment, the second compound is described in Journal of Nuclear Medicine, October 2016, 57 (10) 1599-1606; DOI: htps: / / doi.org / 10.2967 / jnumedJ 15.171678, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound H2N18FNhas a structure whichis (also [18F]MK6240). In an exemplary embodiment, the second compound is described in Journal of Alzheimer’s Disease 31 (2012) 601-612DOI 10.3233 / JAD-2012-120712, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compoundexemplary embodiment, the second compound has a structure which is2H 2 N\ 3HN(also [18F]GTP1). In an exemplary embodiment, the second compound is described in Alzheimer's & Dementia Volume 9. Issue 6, November 2013, 666-676, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which is[18F]Flortaucipir ([18F]AV-1451)TAUVID™. In an exemplaryAtty. Docket: UCSF-849WOembodiment, the second compound is described in Journal of Nuclear Medicine (2018), 59(12), 1869-1876, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which isalso ([18F]RO-948). In an exemplary embodiment, the second compound is described in Kroth et al. Eur J Nucl Med Mol Imaging. 2019;46:2178-2189, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which is(also [18F]PI-2620). In an exemplary embodiment, the secondcompound has a structure which is H (also [11C] Harmine). In an exemplary embodiment, the second compound is described in J. Med. Chem. 2019, 62, 6, 2974- 2987, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which isH (also [18F]JNJ-067). In an exemplary embodiment, the second compound is described in Molecules, 2020 Apr 10;25(7):1750.doi: 0.3390 / molecules25071750, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compound has a structure which isOH(also [18F]APN-1607). In an exemplary embodiment, the second compound is described in Molecules. 2020 AprAtty. Docket: UCSF-849WO10;25(7): 1750.doi: 0.3390 / molecules25071750, the imaging compounds of which are herein incorporated by reference for all purposes. In an exemplary embodiment, the second compoundO. S 1 Nhas a structure which is[18F]APN-1607). In an exemplary embodiment, the second compound is described in US Pat Pub No US 2023 / 174536. the imaging compounds of which are herein incorporated by reference for all purposes, hr an exemplary embodiment, the second compound has a structure which is o(also [18F]ACI-12589).IIIa2. SPECT

[0056] In an exemplary embodiment, the second compound comprises one or more radiolabeled atoms detectable and / or measurable by single photon emission computed tomography (SPECT). In an exemplary embodiment, the second compound is part of a complex, and the complex comprises one or more radiolabeled atoms detectable and / or measurable by SPECT. In an exemplary embodiment, the radiolabeled atoms detectable and / or measurable by SPECT are selected from the group consisting of67Ga,99mTc,111In,123I, or201Tl. In an exemplary embodiment, the radiolabeled atoms detectable and / or measurable by SPECT is "mTc. In an exemplary embodiment, the second compound has a structure which isN NN NAtty. Docket: UCSF-849WOIIIa3. Autoradiography

[0057] In an exemplary embodiment, the second compound comprises one or more radiolabeled atoms detectable and / or measurable by autoradiography. In an exemplary embodiment, the second compound is part of a complex, and the complex comprises one or more radiolabeled atoms detectable and / or measurable by autoradiography. In an exemplary embodiment, the radiolabeled atoms detectable and / or measurable by autoradiography are selected from the group consisting of3H,11C,13N,15O,18F,52Mn,55Co,64Cu,68Ga,82Rb,89Zr. In an exemplary embodiment, the radiolabeled atoms detectable and / or measurable by autoradiography are provided in section IIIa1. In an exemplary embodiment, the second compound has a structurewhich is3H (also [3H]NFT355).Illa.4. First or Second Compounds for use in PET / SPECT / Autoradiography

[0058] When not radiolabeled, the compounds disclosed in this section (IIIa4) can be utilized as a first compound for a method, combination, and / or composition described herein. With radiolabeling, the compounds disclosed in this section (IIIa4) can be utilized as a second compound for a method, combination, and / or composition described herein.

[0059] In an exemplary embodiment, the first compound is a non-radiolabeled compound of the invention, or a non-radiolabeled version of a compound of the invention. In an exemplary embodiment, the first compound is a non-radiolabeled compound described herein, or a non-radiolabeled version of a compound described herein. In an exemplary embodiment, the first compound is a non-radiolabeled compound described herein, or a pharmaceutically acceptable salt or a hydrate or a solvate thereof, or a non-radiolabeled version of a compound described herein, or a pharmaceutically acceptable salt or a hydrate or a solvate thereof. In an exemplary embodiment, the first compound is a non-radiolabeled compound described herein, or a pharmaceutically acceptable salt thereof, or a non-radiolabeled version of a compound described herein, or a pharmaceutically acceptable salt or a hydrate or a solvate thereof. In an exemplary embodiment, the first compound is a non-radiolabeled compound according to a formulaAtty. Docket: UCSF-849WOdescribed herein, or a non-radiolabeled version of a compound described herein. In some embodiments, the first compound is a non-radiolabeled compound according to a formula described herein, or a pharmaceutically acceptable salt or a hydrate or a solvate thereof, or a non-radiolabeled version of a compound described herein, or a pharmaceutically acceptable salt or a hydrate or a solvate thereof. In some embodiments, the first compound is a non-radiolabeled compound according to a formula described herein, or a pharmaceutically acceptable salt thereof, or a non-radiolabeled version of a compound according to a formula described herein, or a pharmaceutically acceptable salt thereof.

[0060] In an exemplary embodiment, the second compound is a radiolabeled compound of the invention, or a radiolabeled version of a compound of the invention. In an exemplary embodiment, the second compound is a radiolabeled compound described herein, or a radiolabeled version of a compound described herein. In an exemplary embodiment, the second compound is a radiolabeled compound described herein, or a pharmaceutically acceptable salt or a hydrate or a solvate thereof, or a radiolabeled version of a compound described herein, or a pharmaceutically acceptable salt or a hydrate or a solvate thereof. In an exemplary embodiment, the second compound is a radiolabeled compound described herein, or a pharmaceutically acceptable salt thereof, or a radiolabeled version of a compound described herein, or a pharmaceutically acceptable salt or a hydrate or a solvate thereof. In an exemplary embodiment, the second compound is a radiolabeled compound according to a formula described herein, or a radiolabeled version of a compound described herein. In some embodiments, the second compound is a radiolabeled compound according to a formula described herein, or a pharmaceutically acceptable salt or a hydrate or a solvate thereof, or a radiolabeled version of a compound described herein, or a pharmaceutically acceptable salt or a hydrate or a solvate thereof. In some embodiments, the second compound is a radiolabeled compound according to a formula described herein, or a pharmaceutically acceptable salt thereof, or a radiolabeled version of a compound according to a formula described herein, or a pharmaceutically acceptable salt thereof.Atty. Docket: UCSF-849WO

[0061] In one aspect, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I):ZT X (I)wherein X is substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazolyl, or substituted or unsubstituted diazaindenyl; Z is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstitutedoN xz \cycloalkyl, or substituted or unsubstituted heterocycloalkyl; Tis RaKA, wherein Rais substituted or unsubstituted Ci-Ce alkyl or substituted or unsubstituted C3-C6 cycloalkyl; Rbis H, halogen, substituted or unsubstituted Ci-Ce alkyl, substituted or unsubstituted Ci-Ce alkoxy, or unsubstituted C3-C6 cycloalkyl.

[0062] In one aspect, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (II):wherein X is substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazolyl, or substituted or unsubstituted diazaindenyl; Z is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocycloalkyl; Rais substituted or unsubstituted Ci-Ce alkyl or substituted or unsubstituted C3-C6 cycloalkyl; Rbis H, halogen, substituted or unsubstituted Ci-Ce alkyl, substituted or unsubstituted Ci-Ce alkoxy, or unsubstituted C3-C6 cycloalkyl.Atty. Docket: UCSF-849WOGroup T

[0063] In an exemplary embodiment, the compound is according to Formula (II) wherein X and Z are as described herein; Rais substituted or unsubstituted Ci-Ce alkyl or substituted or unsubstituted C3-C6 cycloalkyl; Rbis H, halogen, substituted or unsubstituted Ci-Ce alkyl, substituted or unsubstituted Ci-Ce alkoxy, or unsubstituted C3-C6 cycloalkyl. In an exemplary embodiment, the compound is according to Formula (II). wherein X and Z are as described herein; Rais unsubstituted Ci-Ce alkyl, C1-C3 alkyl substituted with one or more halogen and / or C1-C3 alkoxy, unsubstituted cyclopropyl, cyclopropyl substituted with halogen or alkyl, unsubstituted cyclobutyl, or cyclobutyl substituted with halogen or alkyl; Rbis H, fluoro, chloro, unsubstituted Ci-Ce alkyl, C1-C3 alkyl substituted with one or more halogen and / or C1-C3 alkoxy, unsubstituted cyclopropyl, cyclopropyl substituted with halogen or alkyl, unsubstituted cyclobutyl, or cyclobutyl substituted with halogen or alkyl. In an exemplary embodiment, the compound is according to Formula (II), wherein X and Z are as described herein; Rais methyl, ethyl, isopropyl, isobutyl, methoxymethyl, trifluoromethyl, cyclopropyl, fluorocyclopropyl, cyclobutyl, or difluorocyclobutyl, and Rbis H, fluoro, chloro, methyl, ethyl, isopropyl, isobutyl, methoxymethyl, trifluoromethyl, cyclopropyl, fluorocyclopropyl, cyclobutyl, or difluorocyclobutyl.

[0064] In an exemplary embodiment, the compound is according to Formula (I), wherein X and oZ are as described herein, and T is Rb; Rais substituted or unsubstituted Ci-Ce alkyl or substituted or unsubstituted C3-C6 cycloalkyl; Rbis halogen, substituted or unsubstituted Ci-Ce alkyl, substituted or unsubstituted Ci-Ce alkoxy, unsubstituted C3-C6 cycloalkyl. In an exemplary embodiment, the compound is according to Formula (I), wherein X and Z are as described herein, T is as described in this paragraph, Rais unsubstituted Ci-Ce alkyl, C1-C3 alkyl substituted with one or more halogen and / or C1-C3 alkoxy, unsubstituted cyclopropyl, cyclopropyl substituted with halogen or alkyl, unsubstituted cyclobutyl, or cyclobutyl substituted with halogen or alkyl; Rbis fluoro, chloro, unsubstituted Ci-Ce alkyl, C1-C3 alkyl substituted with one or more halogen and / or C1-C3 alkoxy, unsubstituted cyclopropyl, cyclopropyl substituted with halogen or alkyl, unsubstituted cyclobutyl, or cyclobutyl substituted withAtty. Docket: UCSF-849WOhalogen or alkyl. In an exemplary embodiment, the compound is according to Formula (I), wherein X and Z are as described herein, T is as described in this paragraph, Rais methyl, ethyl, isopropyl, isobutyl, methoxymethyl, trifluoromethyl, cyclopropyl, fluorocyclopropyl, cyclobutyl, or difluorocyclobutyl, and Rbis fluoro, chloro, methyl, ethyl, isopropyl, isobutyl, methoxymethyl, trifluoromethyl, cyclopropyl, fluorocyclopropyl, cyclobutyl, or difluorocyclobutyl.

[0065] In an exemplary embodiment, the compound is according to Formula (I), wherein X andZ are as described herein, and T is; Rais as described herein. In an exemplary embodiment, the compound is according to Formula (I), wherein X and Z are as described oherein, and T is In an exemplary embodiment, the compound is according toFormula (I), wherein X and Z are as described herein, and T is Rais substituted or unsubstituted Ci-Ce alkyl or substituted or unsubstituted C3-C6 cycloalkyl. In an exemplary embodiment, the compound is according to Formula (I), wherein X and Z are as described; Rais substituted or unsubstituted C3-C6 cycloalkyl. In an exemplary embodiment, the compound is according to Formula (I), wherein X and Z are asdescribed herein, and T is; Rais substituted or unsubstituted cyclopropyl. In an exemplary embodiment, the compound is according to Formula (I), wherein X and Z are asAtty. Docket: UCSF-849WOdescribed herein, and T is; Rais substituted or unsubstituted cyclobutyl. In an exemplary embodiment, the compound is according to Formula (I), wherein X and Z are as described herein, T is as described in this paragraph, Rais unsubstituted Ci-Ce alkyl, C1-C3 alkyl substituted with one or more halogen and / or C1-C3 alkoxy, unsubstituted cyclopropyl, cyclopropyl substituted with halogen or alkyl, unsubstituted cyclobutyl, or cyclobutyl substituted with halogen or alkyl. In an exemplary embodiment, the compound is according to Formula (I), wherein X and Z are as described herein, and T is as described in this paragraph; Rais methyl, ethyl, isopropyl, isobutyl, methoxymethyl, trifluoromethyl, cyclopropyl, fluorocyclopropyl. cyclobutyl, or difluorocyclobutyl. In an exemplary embodiment, the compound is according toFormula (I), wherein X and Z are as described herein, and T is Ra; Rais fluoro, chloro, unsubstituted C1-C6 alkyl, C1-C3 alkyl is substituted with one or more halogen and / or C1-C3 alkoxy, unsubstituted cyclopropyl, cyclopropyl substituted with halogen or alkyl, unsubstituted cyclobutyl, or cyclobutyl substituted with halogen or alkyl. In an exemplary embodiment, the compound is according to Formula (I), wherein X and Z are as described herein, and T isoRa; Rais fluoro, chloro, methyl, ethyl, isopropyl, isobutyl, methoxymethyl, trifluoromethyl, cyclopropyl, fluorocyclopropyl, cyclobutyl, or difluorocyclobutyl.

[0066] In an exemplary embodiment, the compound is according to Formula (I), wherein X andZ are as described herein, and T is; Rais substituted or unsubstituted Ci-Ce alkyl or substituted or unsubstituted C3-C6 cycloalkyl; Rbis halogen, substituted or unsubstituted Ci-Ce alkyl, substituted or unsubstituted Ci-Ce alkoxy, unsubstituted C3-C6 cycloalkyl. In an exemplary embodiment, the compound is according to Formula (I), wherein X and Z are asAtty. Docket: UCSF-849WOdescribed herein, T is as described in this paragraph, Rais unsubstituted Ci-Ce alkyl, C1-C3 alkyl substituted with one or more halogen and / or C1-C3 alkoxy, unsubstituted cyclopropyl, cyclopropyl substituted with halogen or alkyl, unsubstituted cyclobutyl, or cyclobutyl substituted with halogen or alkyl; Rbis fluoro, chloro, unsubstituted Ci-Ce alkyl, C1-C3 alkyl substituted with one or more halogen and / or C1-C3 alkoxy, unsubstituted cyclopropyl, cyclopropyl substituted with halogen or alkyl, unsubstituted cyclobutyl, or cyclobutyl substituted with halogen or alkyl. In an exemplary embodiment, the compound is according to Formula (I), wherein X and Z are as described herein, and T is as described in this paragraph; Rais methyl, ethyl, isopropyl, isobutyl, methoxymethyl, trifluoromethyl, cyclopropyl, fluorocyclopropyl, cyclobutyl, or difluorocyclobutyl, and Rbis fluoro, chloro, methyl, ethyl, isopropyl, isobutyl, methoxymethyl, trifluoromethyl, cyclopropyl, fluorocyclopropyl, cyclobutyl, or difluorocyclobutyl.

[0067] In an exemplary embodiment, the compound, or a salt, hydrate, or solvate thereof, isaccording to Formula (I), wherein X and Z are as described herein, and T isGroup X

[0068] In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyrazolyl. or substituted or unsubstituted diazaindenyl. In an exemplary embodiment, the compound is according to Formula (I), whereinAtty. Docket: UCSF-849WOT and Z are as described herein, and X is substituted or unsubstituted phenyl or substituted or unsubstituted pyridyl.

[0069] In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is substituted or unsubstituted phenyl. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted phenyl or phenyl substituted with 1, 2, 3, 4 or 5 members independently selected from the group consisting of halogen, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C1-3 alkyl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted C1-3 alkoxy. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted phenyl or phenyl substituted with 1, 2, 3, 4, or 5 members independently selected from the group consisting of halogen, unsubstituted C2-C4 alkenyl, unsubstituted C3-C6 cycloalkyl, unsubstituted C1-3 alkyl, C1-3 alkyl substituted with one or more halogen, unsubstituted C1-3 alkoxy, and C1-3 alkoxy substituted with one or more halogen. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted phenyl or phenyl substituted with 1, 2, 3, 4, or 5 members independently selected from the group consisting of F, Cl, Br, methyl, ethenyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1 -difluoroethyl, cyclopropyl, methoxy, trifluoromethoxy, difluoromethoxy, and 1,1-difluoroethoxy.

[0070] In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted phenyl. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X isRfR9according to:R1wherein Rf, Rg, and R11are each independently selected from the group consisting of H, halogen, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C1-3 alkyl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted C1-3 alkoxy, wherein at least one of Rf, Rg, and Rhis not H. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein,Atty. Docket: UCSF-849WOv / T Rg*'and X is according to:Rhwherein Rf, Rg, and R11are each independently selected from the group consisting of H, halogen, C2-C4 alkenyl, C3-C6 cycloalkyl, unsubstituted C1-3 alkyl, C1-3 alkyl substituted with one or more halogen, unsubstituted C1-3 alkoxy, and C1-3 alkoxy substituted with one or more halogen, wherein at least one of Rf, R8, and Rhis not H. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as Yy / R3described herein, and X is according to: Rhwherein Rf, Rg, and Rhare each independently selected from the group consisting of H, F, Cl, Br, methyl, ethenyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1 -difluoroethyl, cyclopropyl, methoxy, trifluoromethoxy, difluoromethoxy, and 1.1 -difluoroethoxy, wherein at least one of Rf, R8, and Rhis not H. In an exemplary embodiment, the compound is according to Formula (I), wherein TRgand Z are as described herein, and X is according to:Rhwherein Rf, Rg, and Rhare each independently selected from the group consisting of H, F, Cl, methyl, isopropyl, trifluoromethyl, trifluoromethoxy, and difluoromethoxy, wherein at least one of Rf, R8, and Rhis not H.

[0071] In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is substituted or unsubstituted pyridyl. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted pyridyl or pyridyl substituted with 1, 2, 3, or 4 members independently selected from the group consisting of halogen, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C1-3 alkyl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted C1-3 alkoxy. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted pyridylAtty. Docket: UCSF-849WOor pyridyl substituted with 1, 2, 3, or 4 members independently selected from the group consisting of halogen, unsubstituted C2-C4 alkenyl, unsubstituted C3-C6 cycloalkyl, unsubstituted C1-3 alkyl, C1-3 alkyl substituted with one or more halogen, unsubstituted C1-3 alkoxy, and C1-3 alkoxy substituted with one or more halogen. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted pyridyl or pyridyl substituted with one or more members independently selected from the group consisting of F, Cl, Br, methyl, ethenyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1 -difluoroethyl, cyclopropyl, methoxy, trifluoromethoxy, difluoromethoxy, and 1,1-difluoroethoxy.

[0072] In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted pyridyl. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X isaccording to: / r R9R' wherein R and R8are each independently selected from the group consisting of H, halogen, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C1-3 alkyl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted C1-3 alkoxy, wherein at least one of Rfand R8is not H. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is according to: Vy*R9wherein R and R8are each independently selected from the group consisting of H, halogen, unsubstituted C2-C4 alkenyl, unsubstituted C3-C6 cycloalkyl, unsubstituted C1-3 alkyl, C1-3 alkyl substituted with one or more halogen, unsubstituted C1-3 alkoxy, and C1-3 alkoxy substituted with one or more halogen, wherein at least one of Rfand Rgis not H. In an exemplary embodiment, the compound is according to Formula (I), wherein T andZ are asdescribed herein, and X is according to:R9wherein Rfand Rgare eachAtty. Docket: UCSF-849WOindependently selected from the group consisting of H, F, Cl, Br, methyl, ethenyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1 -difluoroethyl, cyclopropyl, methoxy, trifluoromethoxy, difluoromethoxy, and 1.1 -difluoroethoxy, wherein at least one of Rfand Rgis not H. In an exemplary embodiment, the compound is according to Formula (I), wherein T andZ are as described herein, and X is according to:Rgwherein Rfand Rgare each independently selected from the group consisting of H, F, methyl, ethenyl, isopropyl, trifluoromethyl, and 1,1-difluoroethyl, wherein at least one of Rfand Rgis not H.

[0073] In an exemplary embodiment, the compound is according to Formula (I), wherein T andzYvRf / RgZ are as described herein, and X is according to:Rhwherein Rf, Rg, and Rhare each independently selected from the group consisting of H, halogen, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C1-3 alkyl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted C1-3 alkoxy, wherein at least one of Rf, Rg, and Rhis not H. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are asdescribed herein, and X is according to:Rhwherein Rf, Rg, and Rhare each independently selected from the group consisting of H, halogen, unsubstituted C2-C4 alkenyl, unsubstituted C3-C6 cycloalkyl, unsubstituted C1-3 alkyl, C1-3 alkyl substituted with one or more halogen, unsubstituted C1-3 alkoxy, and C1-3 alkoxy substituted with one or more halogen, wherein at least one of Rf, Rg, and Rhis not H. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is according to:Atty. Docket: UCSF-849WOrvRf / R9Rhwherein Rf, Rg, and Rhare each independently selected from the group consisting of H, F, Cl, Br, methyl, ethenyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1-difluoroethyl, cyclopropyl, methoxy, trifluoromethoxy, difluoromethoxy, and 1,1-difluoroethoxy, wherein at least one of Rf, Rg, and Rhis not H. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X isaccording to:Rhwherein Rf, Rg, and Rhare each independently selected from the group consisting of H, Cl, and trifluoromethyl, wherein at least one of Rf, Rg, and Rhis not H.

[0074] In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is substituted or unsubstituted pyrazolyl. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted pyrazolyl or pyrazolyl substituted with 1, 2, or 3 members independently selected from the group consisting of halogen, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C1-3 alkyl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted C1-3 alkoxy. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted pyrazolyl or pyrazolyl substituted with 1, 2, or 3 members independently selected from the group consisting of halogen, unsubstituted C2-C4 alkenyl, unsubstituted C3-C6 cycloalkyl, unsubstituted C1-3 alkyl, C1-3 alkyl substituted with one or more halogen, unsubstituted C1-3 alkoxy, and C1-3 alkoxy substituted with one or more halogen. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted pyrazolyl or pyrazolyl substituted with 1, 2, or 3 members independently selected from the group consisting of F, Cl, Br, methyl, ethenyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1 -difluoroethyl, cyclopropyl, methoxy, trifluoromethoxy, difluoromethoxy, and 1,1-difluoroethoxy.Atty. Docket: UCSF-849WO

[0075] In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X is unsubstituted pyrazolyl. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are as described herein, and X isI \R"' / Raccording to: Rgwherein Rgand Rhare each independently selected from the group consisting of H, halogen, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C1-3 alkyl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted C1-3 alkoxy, and Rfis selected from the group consisting of H, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C1-3 alkyl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted C1-3 alkoxy, wherein at least one of Rf, Rg, and Rhis not H. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are asN^Rfdescribed herein, and X is according to:Rgwherein Rgand Rhare each independently selected from the group consisting of H, halogen, unsubstituted C2-C4 alkenyl, unsubstituted C3-C6 cycloalkyl, unsubstituted C1-3 alkyl, C1-3 alkyl substituted with one or more halogen, unsubstituted C1-3 alkoxy, and C1-3 alkoxy substituted with one or more halogen, and Rfis selected from the group consisting of H, unsubstituted C2-C4 alkenyl, unsubstituted C3-C6 cycloalkyl, unsubstituted C1-3 alkyl, C1-3 alkyl substituted with one or more halogen, unsubstituted C1-3 alkoxy, and C1-3 alkoxy substituted with one or more halogen, wherein at least one of Rf, Rg, and Rhis not H. In an exemplary embodiment, the compound is according toFormula (I), wherein T and Z are as described herein, and X is according to:Rgwherein Rgand Rhare each independently selected from the group consisting of H, F, Cl, Br, methyl, ethenyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1-difluoroethyl, cyclopropyl, methoxy, trifluoromethoxy, difluoromethoxy, and 1,1-difluoroethoxy, and RfisAtty. Docket: UCSF-849WOselected from the group consisting of H, methyl, ethenyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1 -difluoroethyl, cyclopropyl, methoxy, trifluoromethoxy, difluoromethoxy, and 1.1 -difluoroethoxy, wherein at least one of Rf, Rg, and Rhis not H. In an exemplary embodiment, the compound is according to Formula (I), wherein T and Z are asdescribed herein, and X is according to:wherein Rfis methyl, ethenyl, isopropyl, difluoromethyl, trifluoromethyl, and 1,1 -difluoroethyl.

[0076] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is substituted or unsubstituted diazaindenyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is substituted or unsubstituted pyrazolo[1.5-a]pyridine. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is diazaindenyl substituted with 1, 2, 3, or 4 members independently selected from the group consisting of halogen, substituted or unsubstituted C2-C4 alkenyl, substituted or unsubstituted C1-3 alkyl, substituted or unsubstituted C3-6 cycloalkyl, and substituted or unsubstituted C1-3 alkoxy. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is diazaindenyl substituted with 1, 2, 3, or 4 members independently selected from the group consisting of halogen, unsubstituted C2-C4 alkenyl, unsubstituted C3-C6 cycloalkyl, unsubstituted C1-3 alkyl, C1-3 alkyl substituted with one or more halogen, unsubstituted C1-3 alkoxy, and C1-3 alkoxy substituted with one or more halogen. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is diazaindenyl substituted with 1, 2, 3, or 4 members independently selected from the group consisting of F, Cl, Br, methyl, ethenyl, isopropyl, fluoromethyl, difluoromethyl, trifluoromethyl, 1,1 -difluoroethyl, cyclopropyl, methoxy, trifluoromethoxy, difluoromethoxy, and 1,1-difluoroethoxy.

[0077] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X isAtty. Docket: UCSF-849WOphenyl, 4-(trifluoromethyl)phenyl, 4-fluorophenyl, 4-chlorophenyl, 4-chloro-3-fluorophenyl, 4-chloro-3,5-difluorophenyl, 3,5-difluorophenyl, 4-methyl-3,5-difluorophenyl, 3-chloro-(4-cyclopropyl)phenyl, 3-fluoro-(4-fluoromethyl)phenyl, 3-fluoro-(4-difluoromethyl)phenyl, 4-(difluoromethyl)phenyl, 4-(methyl)phenyl, 3,4-difluorophenyl, 4-cyclopropyl-3-fluorophenyl, 3-fluoro-(4-methyl)phenyl, 3-fluoro-(4-methoxy)phenyl, 4-fluoro-5-methylpyridin-2-yl, 6-(trifluoromethyl)pyridin-3-yl. 5-trifluoromethylpyridin-2-yl, l-(difluoromethyl)-lH-pyrazolyl, or pyrazolo[l,5-a]pyridyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is phenyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is 4-(trifluoromethyl)phenyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is 4-fluorophenyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is 4-chlorophenyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is 4-chloro-3-fluorophenyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is 4-chloro-3,5-difluorophenyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and Z are as described herein, and X is 4-methyl-3,5-difluorophenyl.Group Z:

[0078] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, or substituted or unsubstituted heterocycloalkyl.

[0079] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted azaindenyl, substituted or unsubstituted diazaindenyl, substituted or unsubstituted triazaindenyl, substituted or unsubstituted tetraazaindenyl, substituted or unsubstitutedAtty. Docket: UCSF-849WOisoquinolyl, substituted or unsubstituted indazolyl, substituted or unsubstituted pyrazolyl, substituted or unsubstituted benzotriazolyl, substituted or unsubstituted triazolyl, substituted or unsubstituted benzimidazolyl, substituted or unsubstituted quinolyl, substituted or unsubstituted naphthyl, substituted or unsubstituted diazanaphthyl, substituted or unsubstituted diazabicyclooctadienyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted pyrimidinyl, substituted or unsubstituted tolyl, substituted or unsubstituted isoindolinyl, substituted or unsubstituted isonicotinamide, substituted or unsubstituted benzoxazolyl, substituted or unsubstituted quinoxalinyl, substituted or unsubstituted benzofuranyl, substituted or unsubstituted oxaazanaphthyl, substituted or unsubstituted xyxyl, substituted or unsubstituted biphenylyl, substituted or unsubstituted furyl, or substituted or unsubstituted cinnolinyl.

[0080] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted azaindenyl, substituted or unsubstituted diazaindenyl, substituted or unsubstituted triazaindenyl, substituted or unsubstituted tetraazaindenyl, substituted or unsubstituted isoquinolyl, substituted or unsubstituted quinolyl, substituted or unsubstituted indazolyl, and substituted or unsubstituted pyrazolyl.

[0081] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is substituted or unsubstituted pyrazolo[l,5-a]pyrimidinyl, substituted or unsubstituted pyrazolo[1.5-a]pyrazinyl, substituted or unsubstituted isoquinolinyl, substituted or unsubstituted benzo[d]oxazolyl, substituted or unsubstituted lH-pyrazolo[3,4-c]pyridinyl, substituted or unsubstituted isoindolinone, substituted or unsubstituted phenyl, substituted or unsubstituted 1H-indazolyl, substituted or unsubstituted IH-pyrrolo[2,3-c]pyridinyl, substituted or unsubstituted IH-pyrazolyl, substituted or unsubstituted 3,4-dihydroisoquinolin-l(2H)-one, substituted or unsubstituted pyridin-2-yl, or substituted or unsubstituted isoindolin-l-onelyl.

[0082] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is substituted or unsubstituted pyrazolo[l,5-a]pyrimidin-2-yl, substituted or unsubstituted pyrazolo[1.5-a]pyrazin-2-yl, substituted or unsubstituted isoquinolin-3-yl, substituted orAtty. Docket: UCSF-849WOunsubstituted benzo [d] ox azol -6-yl, substituted or unsubstituted lH-pyrazolo[3,4-c]pyridin-5-yl, substituted or unsubstituted isoindolin-l-one, substituted or unsubstituted lH-indazol-5-yl, substituted or unsubstituted lH-pyrrolo[2,3-c]pyridin-5-yl. substituted or unsubstituted 1H-pyrazol-3-yl, substituted or unsubstituted lH-indazol-6-yl, substituted or unsubstituted 3,4-dihydroisoquinolin-l(2H)-one, substituted or unsubstituted lH-pyrazol-3-yl, pyridinyl substituted lH-pyrazol-3-yl, substituted or unsubstituted isoindolin-l-onel-5-yl, or substituted or unsubstituted pyrazolo[l,5-a]pyrimidin-2-yl).

[0083] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is methyl substituted pyrazolo[l,5-a]pyrimidin-2-yl, trifluoromethyl substituted pyrazolo[l,5-a]pyrimidin-2-yl, dimethyl substituted pyrazolo[l,5-a]pyrazin-2-yl, isoquinolin-3-yl, methyl substituted benzo[d]oxazol-6-yl, methyl substituted lH-pyrazolo[3,4-c]pyridin-5-yl. methyl substituted isoindolin-l-one, difluoromethyl substituted phenyl, methyl substituted IH-indazol-5-yl, methyl substituted lH-pyrrolo[2,3-c]pyridin-5-yl, (pyridin-3-yl) substituted lH-pyrazol-3-yl, methyl substituted lH-indazol-6-yl, methyl substituted 3.4-dihydroisoquinolin-l(2H)-one. dihaloethyl substituted- lH-pyrazol-3-yl, dihalomethyl substituted- lH-pyrazol-3-yl, acetamidyl, halo substituted pyridin-2-yl, methyl substituted isoindolin-l-onel-5-yl, or halomethyl, methyl substituted pyrazolo[l,5-a]pyrimidin-2-yl).

[0084] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is 7-methyl pyrazolo[l,5-a]pyrimidin-2-yl, 5,7-dimethyl pyrazolo[l,5-a]pyrimidin-2-yl, 7-trifluoromethyl pyrazolo[l,5-a]pyrimidin-2-yl, 4,6-dimethyl pyrazolo[l,5-a]pyrazin-2-yl, isoquinolin-3-yl, 2-methyl benzo [d]oxazol-6-yl, 1-methyl lH-pyrazolo[3,4-c]pyridin-5-yl, 2-methyl isoindolin-l-one, 4-difluoromethyl phenyl, 1-methyl lH-indazol-5-yl, 1-methyl 1H-pyrrolo[2,3-c]pyridin-5-yl, (pyridin-3-yl) lH-pyrazol-3-yl, 1-methyl lH-indazol-6-yl, 2-methyl 3,4-dihydroisoquinolin-l(2H)-one, l-(2,2-difluoroethyl)-lH-pyrazol-3-yl, 4-acetamidyl-5-fluoro-pyridin-2-yl, 2-methyl isoindolin-l-onel-5-yl, 7-(fluoromethyl)-5-methylpyrazolo[l,5-a]pyrimidin-2-yl, or 5-(fluoromethyl)-7-methylpyrazolo[1,5-a]pyrimidin-2-yl.

[0085] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z isAtty. Docket: UCSF-849WOsubstituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted azaindenyl, substituted or unsubstituted diazaindenyl, substituted or unsubstituted triazaindenyl, substituted or unsubstituted isoquinolyl, or substituted or unsubstituted quinolyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is unsubstituted aryl, unsubstituted heteroaryl, unsubstituted cycloalkyl, or unsubstituted heterocycloalkyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is unsubstituted phenyl, unsubstituted pyridyl, unsubstituted azaindenyl, unsubstituted diazaindenyl, unsubstituted triazaindenyl, unsubstituted tetraazaindenyl, unsubstituted isoquinolyl, unsubstituted indazolyl, unsubstituted pyrazolyl, unsubstituted benzotriazolyl, unsubstituted triazolyl, unsubstituted benzimidazolyl, unsubstituted quinolyl, unsubstituted naphthyl, unsubstituted diazanaphthyl, unsubstituted diazabicyclooctadienyl, unsubstituted thiazolyl, unsubstituted pyrimidinyl, unsubstituted tolyl, unsubstituted isoindolinyl, unsubstituted isonicotinamide, unsubstituted benzoxazolyl, unsubstituted quinoxalinyl, unsubstituted benzofuranyl, unsubstituted oxaazanaphthyl, unsubstituted xyxyl, unsubstituted biphenylyl, unsubstituted furyl, or unsubstituted cinnolinyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is unsubstituted phenyl, unsubstituted pyridyl, unsubstituted azaindenyl, unsubstituted diazaindenyl, unsubstituted triazaindenyl, unsubstituted tetraazaindenyl, unsubstituted isoquinolyl, unsubstituted quinolyl, unsubstituted indazolyl, and unsubstituted pyrazolyl. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is unsubstituted phenyl, unsubstituted pyridyl, unsubstituted azaindenyl, unsubstituted diazaindenyl, unsubstituted triazaindenyl, unsubstituted isoquinolyl, or unsubstituted quinolyl.

[0086] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is a substituted ring system as described in this section entitled “Group Z:”, and the substitution is one, two, or three members independently selected from the group consisting of nitro, cyano, halogen, Ci-6 alkyl, halogen substituted Ci-6 alkyl, hydroxy substituted Ci-6 alkyl, Ci-6 alkoxy substituted Ci-6 alkyl, C3-6 cycloalkyl substituted C1-6 alkyl, azetidinyl substituted C1-6 alkyl, C2-6Atty. Docket: UCSF-849WOalkenyl, halogen substituted C2-6 alkenyl, hydroxy substituted C2-6 alkenyl, C1-6 alkoxy substituted C2-6 alkenyl, C3-6 cycloalkyl substituted C2-6 alkenyl, azetidinyl substituted C2-6 alkenyl, C2-6 alkynyl, halogen substituted C2-6 alkynyl, hydroxy substituted C2-6 alkynyl, C1-6 alkoxy substituted C2-6 alkynyl, C3-6 cycloalkyl substituted C2-6 alkynyl, azetidinyl substituted C2 6 alkynyl, C3-6 cycloalkyl, C1-6 alkyl substituted C3-6 cycloalkyl, halogen substituted C3-6 cycloalkyl, hydroxy substituted C3-6 cycloalkyl, C1-6 alkoxy substituted C3-6 cycloalkyl, azetidinyl substituted C3-6 cycloalkyl, C1-6 alkoxy, halogen substituted C1-6 alkoxy, hydroxy substituted C1-6 alkoxy, C3-6 cycloalkyl substituted C1-6 alkoxy, azetidinyl substituted C1-6 alkoxy, C3-6 cycloalkoxy, C1-6 alkyl substituted C3-6 cycloalkoxy, halogen substituted C3-6 cycloalkoxy, hydroxy substituted C3-6 cycloalkoxy, C1-6 alkoxy substituted C3-6 cycloalkoxy, azetidinyl substituted C3-6 cycloalkoxy, azetidinyl, C1-6 alkyl substituted azetidinyl, halogen substituted azetidinyl, hydroxy substituted azetidinyl, C1-6 alkoxy substituted azetidinyl, and C3-6 cycloalkyl substituted azetidinyl.

[0087] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is a substituted ring system as described in this section entitled “Group Z:”, and the substitution is one. two, or three members independently selected from the group consisting of nitro, cyano, halogen, C1-6 alkyl, fluoro substituted C1-6 alkyl, chloro substituted C1-6 alkyl, hydroxy substituted C1-6 alkyl, methoxy substituted C1-6 alkyl, ethoxy substituted C1-6 alkyl, cyclopropyl substituted C1-6 alkyl, cyclobutyl substituted C1-6 alkyl, azetidinyl substituted C1-6 alkyl, C2-6 alkenyl, fluoro substituted C2-6 alkenyl, chloro substituted C2-6 alkenyl, hydroxy substituted C2-6 alkenyl, methoxy substituted C2-6 alkenyl, ethoxy substituted C2-6 alkenyl, cyclopropyl substituted C2-6 alkenyl, cyclobutyl substituted C2-6 alkenyl, azetidinyl substituted C2-6 alkenyl, C2-6 alkynyl, fluoro substituted C2-6 alkynyl, chloro substituted C2-6 alkynyl, hydroxy substituted C2-6 alkynyl, methoxy substituted C2-6 alkynyl, ethoxy substituted C2-6 alkynyl, cyclopropyl substituted C2-6 alkynyl, cyclobutyl substituted C2-6 alkynyl, azetidinyl substituted C2-6 alkynyl, C3-6 cycloalkyl, methyl substituted C3-6 cycloalkyl, ethyl substituted C3-6 cycloalkyl, isopropyl substituted C3-6 cycloalkyl, fluoro substituted C3-6 cycloalkyl, chloro substituted C3-6 cycloalkyl, hydroxy substituted C3-6 cycloalkyl, methoxy substituted C3-6 cycloalkyl, ethoxy substituted C3-6 cycloalkyl, azetidinyl substituted C3-6 cycloalkyl, C1-6 alkoxy, fluoro substituted C1-6 alkoxy, chloro substituted C1-6 alkoxy, hydroxy substituted C1-6 alkoxy, cyclopropyl substituted C1-6Atty. Docket: UCSF-849WOalkoxy, cyclobutyl substituted Ci-6 alkoxy, azetidinyl substituted Ci-6 alkoxy, C3-6 cycloalkoxy, methyl substituted C3-6 cycloalkoxy, ethyl substituted C3-6 cycloalkoxy, isopropyl substituted C3-6 cycloalkoxy, fluoro substituted C3-6 cycloalkoxy, chloro substituted C3-6 cycloalkoxy, hydroxy substituted C3-6 cycloalkoxy, methoxy substituted C3-6 cycloalkoxy, ethoxy substituted C3-6 cycloalkoxy, azetidinyl substituted C3-6 cycloalkoxy, azetidinyl, methyl substituted azetidinyl, ethyl substituted azetidinyl, isopropyl substituted azetidinyl, fluoro substituted azetidinyl, chloro substituted azetidinyl, hydroxy substituted azetidinyl, methoxy substituted azetidinyl, ethoxy substituted azetidinyl, cyclopropyl substituted azetidinyl, and cyclobutyl substituted azetidinyl.

[0088] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is a substituted ring system as described in this section entitled “Group Z:”, and the substitution is one. two, or three members independently selected from the group consisting of nitro, cyano, fluoro, chloro, C1-3 alkyl, halogen substituted C1-3 alkyl, hydroxy substituted C1-3 alkyl, C1-6 alkoxy substituted C1-3 alkyl, C3-6 cycloalkyl substituted C1-3 alkyl, azetidinyl substituted C1-3 alkyl, C2-4 alkenyl, halogen substituted C2-4 alkenyl, hydroxy substituted C2-4 alkenyl, C1-6 alkoxy substituted C2-4 alkenyl, C3-6 cycloalkyl substituted C2-4 alkenyl, azetidinyl substituted C2-4 alkenyl, C2-4 alkynyl, halogen substituted C2-4 alkynyl, hydroxy substituted C2-4 alkynyl, C1-6 alkoxy substituted C2-4 alkynyl, C3-6 cycloalkyl substituted C2-4 alkynyl, azetidinyl substituted C2 4 alkynyl, C3-4 cycloalkyl, C1-6 alkyl substituted C3-4 cycloalkyl, halogen substituted C3-4 cycloalkyl, hydroxy substituted C3-4 cycloalkyl, C1-6 alkoxy substituted C3-4 cycloalkyl, azetidinyl substituted C3-4 cycloalkyl, C1-3 alkoxy, halogen substituted C1-3 alkoxy, hydroxy substituted C1-3 alkoxy, C3-6 cycloalkyl substituted C1-3 alkoxy, azetidinyl substituted C1-3 alkoxy, C3-4 cycloalkoxy, C1-6 alkyl substituted C3-4 cycloalkoxy, halogen substituted C3-4 cycloalkoxy, hydroxy substituted C3-4 cycloalkoxy, C1-6 alkoxy substituted C3-4 cycloalkoxy, azetidinyl substituted C3-4 cycloalkoxy, azetidinyl, C1-6 alkyl substituted azetidinyl, halogen substituted azetidinyl, hydroxy substituted azetidinyl, C1-6 alkoxy substituted azetidinyl, and C3-6 cycloalkyl substituted azetidinyl.

[0089] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is a substituted ring system as described in this section entitled “Group Z:”, and the substitution is one, two, or three members independently selected from the group consisting of nitro, cyano,Atty. Docket: UCSF-849WOfluoro, chloro, C1-3 alkyl, fluoro substituted C1-3 alkyl, chloro substituted C1-3 alkyl, hydroxy substituted C1-3 alkyl, methoxy substituted C1-3 alkyl, ethoxy substituted C1-3 alkyl, cyclopropyl substituted C1-3 alkyl, cyclobutyl substituted C1-3 alkyl, azetidinyl substituted C1-3 alkyl, C2-4 alkenyl, fluoro substituted C2-4 alkenyl, chloro substituted C2-4 alkenyl, hydroxy substituted C2-4 alkenyl, methoxy substituted C2-4 alkenyl, ethoxy substituted C2-4 alkenyl, cyclopropyl substituted C2-4 alkenyl, cyclobutyl substituted C2-4 alkenyl, azetidinyl substituted C2-4 alkenyl, C2-4 alkynyl, fluoro substituted C2-4 alkynyl, chloro substituted C2-4 alkynyl, hydroxy substituted C2-4 alkynyl, methoxy substituted C2-4 alkynyl, ethoxy substituted C2-4 alkynyl, cyclopropyl substituted C2-4 alkynyl, cyclobutyl substituted C2-4 alkynyl, azetidinyl substituted C2-4 alkynyl, C3-4 cycloalkyl, methyl substituted C3-4 cycloalkyl, ethyl substituted C3-4 cycloalkyl, isopropyl substituted C3-4 cycloalkyl, fluoro C3-4 cycloalkyl, chloro C3-4 cycloalkyl, hydroxy substituted C3-4 cycloalkyl, methoxy substituted C3-4 cycloalkyl, ethoxy substituted C3-4 cycloalkyl, azetidinyl substituted C3-4 cycloalkyl, C1-3 alkoxy, fluoro substituted C1-3 alkoxy, chloro substituted C1-3 alkoxy, hydroxy substituted C1-3 alkoxy, cyclopropyl substituted C1-3 alkoxy, cyclobutyl substituted C1-3 alkoxy, azetidinyl substituted C1-3 alkoxy, C3-4 cycloalkoxy, methyl substituted C3-4 cycloalkoxy, ethyl substituted C3-4 cycloalkoxy, fluoro substituted C3-4 cycloalkoxy, chloro substituted C3-4 cycloalkoxy, hydroxy substituted C3-4 cycloalkoxy, methoxy substituted C3-4 cycloalkoxy, ethoxy substituted C3-4 cycloalkoxy, azetidinyl substituted C3-4 cycloalkoxy, azetidinyl, methyl substituted azetidinyl, ethyl substituted azetidinyl, fluoro substituted azetidinyl, chloro substituted azetidinyl, hydroxy substituted azetidinyl, methoxy substituted azetidinyl, ethoxy substituted azetidinyl, cyclopropyl substituted azetidinyl, and cyclobutyl substituted azetidinyl.

[0090] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is a substituted ring system as described in this section entitled “Group Z:”, and the substitution is one, two, or three members independently selected from the group consisting of nitro, cyano, fluoro, chloro, methyl, ethyl, isopropyl, trifluoromethyl, difluoromethyl, fluoromethyl, 1-fluoroethyl, 2-fluoroethyl, 1,1 -difluoroethyl, 1 -hydroxy ethyl, 2-hydroxyethyl, methoxy ethyl, hydroxymethyl, vinyl, ethynyl, 1-propynyl, 2-cyclopropylethynyl, cyclopropyl, cyclobutyl, azetidinyl, 1 -methylcyclopropyl, methoxy, difluoromethoxy, 2-fluoroethoxy, cyclopropoxy, and ( 1 -azetidinyl)carbonyl.Atty. Docket: UCSF-849WO

[0091] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (I), wherein T and X are as described herein, and Z is l-(2-methoxyethyl)-lH-l,2,6-triazainden-5-yl, l-(2-methoxyethyl)-6-isoquinolyl, 1- (trifluoromethyl) -6-isoquinolyl, l-cyclopropyl-lH-indazol-5-yl, l-cyclopropyl-4-pyrazolyl, l-fluoro-6-isoquinolyl, 1 -isoquinolyl, l-methoxy-6-isoquinolyl, 1 -methyl- l,5-diaza-6-indanyl, 1-methyl- l,6-diaza-5-indanyl, l-methyl-lH-l,2,3-benzotriazol-5-yl. l-methyl-lH-l,2,4-triazainden-3-yl, 1-methyl-lH-l,2,4-triazainden-5-yl, l-methyl-lH-l,2,4-triazol-3-yl, l-methyl-lH-l,2,4,6-tetraazainden-5-yl, 1 -methyl- 1H-1, 2, 5-triazainden-3-yl, l-methyl-lH-l,2,5-triazainden-4-yl, 1-methyl- 1H- 1,2,5-triazainden-6-yl, 1 -methyl- 1H-1, 2, 6-triazainden-3-yl, l-methyl-lH-l,2,6-triazainden-5-yl, 1-methyl-lH-l,2,6-triazainden-5-yl), 1-methyl- 1H-1, 2, 7-triazainden-3-yl, 1-methyl- 1H-1, 2, 7-triazainden-5-yl, l-methyl-lH-l,3-benzimidazol-5-yl, l-methyl-lH-l,3,5-triazainden-6-yl, 1-methyl- 1H- 1,4-diazainden-3-yl, 1 -methyl- 1H- 1,4-diazainden-5-yl, 1 -methyl- 1 H- 1,4,6-triazainden-5-yl, l-methyl-lH-l,5-diazainden-6-yl, l-methyl-lH-l,6-diazainden-3-yl, 1-methyl-lH-l,6-diazainden-5-yl. l-methyl-lH-l,7-diazainden-5-yl. 1-methyl- lH-indazol-5-yl. 1-methyl-lH-indazol-6-yl, l-methyl-2-oxo-6-quinolyl, l-methyl-3-methyl-lH-indazol-5-yl, l-methyl-4-methyl-3-pyrazolyl, l-methyl-4-pyrazolyl, l-methyl-5-methyl-3-pyrazolyl, l-methyl-6-isoquinolyl, l-methyl-7-isoquinolyl, 1-naphthyl, l-oxa-4-aza-2-indenyl, l-oxa-4-aza-6-indenyl, 1-oxa-5-aza-6-indenyl, l-oxa-6-aza-5-indanyl, l-oxa-7-aza-5-indanyl, l-oxa-7-aza-6-indanyl, l,l-difluoro-4-aza-5-indanyl, l,2-diazabicyclo[3.3.0]octa-2,4-dien-3-yl, 1,2-diazabicyclo[3.3.0]octa-2,4-dien-4-yl, l,3-benzoxazol-2-yl, l,3,3a-triaza-2-indenyl, 1,3,3a-triaza-6-indenyl, l,3a-diaza-2-indenyl, l,3a-diaza-6-indenyl, l,3a,4-triaza-2-indenyl, 1,3a, 4-triaza-3-indenyl, l,3a,6-triaza-5-indenyl, l,4-diazabicyclo[3.3.0]octa-2,4-dien-3-yl, l,4,7a-triaza- 2-indenyl, l,4,7a-triaza-3-indenyl, l,4,7a-triaza-5-indenyl, l,4,7a-triaza-6-indenyl, l,5-diaza-3-naphthyl, l,5,7a-triaza-4-indenyl, l,6-diaza-3-naphthyl, l,7a-diaza-2-indenyl, l,7a-diaza-6-indenyl, 2-(l-methylcyclopropyl)-4-pyridyl. 2-(l-propynyl)-4-pyridyl, 2-(2-cyclopropylethynyl)-4-pyridyl, 2-(difluoromethyl)-4-pyridyl, 2-(trifluoromethyl)-4-pyridyl, 2-(trifluoromethyl)-4-pyrimidinyl, 2-(trifluoromethyl)-6-quinolyl, 2-chloro-3-fluoro-4-pyridyl, 2-chloro-4-pyridyl, 2-chloro-6-methyl-4-pyridyl, 2-cyclobutyl-4-pyridyl, 2-cyclopropoxy-4-pyridyl, 2-cyclopropyl-l,3-thiazol-4-yl, 2-cyclopropyl-l,3-thiazol-5-yl, 2-cyclopropyl-4-pyridyl, 2-cyclopropyl-4-pyrimidinyl, 2-cyclopropyl-5-fluoro-4-pyrimidinyl, 2-difluoromethoxy-4-pyridyl, 2-ethyl-4-pyridyl, 2-ethyl-4-pyrimidinyl, 2-ethyl-5-fluoro-4-pyrimidinyl, 2-ethynyl-4-pyridyl, 2-ethynyl-5-Atty. Docket: UCSF-849WOfluoro-4-pyridyl, 2-ethynyl-6-fluoro-4-pyridyl, 2-fluoro-3-tolyl, 2-fluoro-5-tolyl, 2-fluoro-6-methyl-4-pyridyl, 2-fluoro-6-quinolyl, 2-fluoro-6-vinyl-4-pyridyl, 2-isoindolinyl, 2-isonicotinamide, 2-isopropyl-4-pyridyl, 2-methoxy-4-pyridyl, 2-methoxy-4-pyrimidinyl, 2-methoxy-6-quinolyl, 2-methyl- 1 -oxo-6-isoquinolyl, 2-methyl- 1,3-benzoxazol-6-yl, 2-methyl- 1,3-thiazol-4-yl, 2-methyl- l,3-thiazol-5-yl, 2-methyl- l,3a-diaza-5-indenyl, 2-methyl-l,3a,6-triaza-5-indenyl, 2-methyl-2H- 1,2,4-triazainden-5-yl, 2-methyl-2H- 1,2,5-triazainden-4-yl, 2-methyl-2H-l,2,6-triazainden-5-yl, 2-methyl-2H-indazol-5-yl, 2-methyl-2H-indazol-6-yl, 2-methyl-4-pyridyl, 2-methyl-4-pyrimidinyl, 2-methyl-6-quinolyl, 2-methyl-7-quinolyl, 2-naphthyl, 2-phenyl, 2-pyridyl, 2-quinolyl, 2-quinoxalinyl, 2,3-dihydro-l-benzofuran-4-yl, 2,3-dihydro-l-benzofuran-5-yl, 2,3-dihydro-l-benzofuran-6-yl, 2,4-diaza-2-indanyl, 2,6-dichloro-4-pyridyl, 2,6-dimethyl-4-pyridyl. 2,6-dimethyl-4-pyrimidinyl, 3-biphenylyl, 3-chloro-6-isoquinolyl, 3-chloro-6-methyl-2-pyridyl, 3-cyclopropyl-l,4,7a-triaza-6-indenyl, 3-fluoro-4-methyl-2-pyridyl, 3-fluoro-5-tolyl, 3-fluoro-6-methyl-2-pyridyl, 3-methyl-l,3a-diaza-5-indenyl, 3-methyl-l,3a-diaza-6-indenyl, 3-methyl-2,3a,6-triaza-7-indenyl. 3-methyl-6-isoquinolyl, 3-methyl-6-quinolyl, 3-oxo-4-aza-5-indanyl, 3-quinolyl, 3,3-difluoro-4-aza-5-indanyl, 3,3-difluoro-5-aza-6-indanyl, 3,4-dihydro-2H-l-oxa-7-azanaphth-6-yl, 3,4-dimethyl-l-pyrazolyl, 3,5-xylyl, 3a,4,6-triaza-2-indenyl, 4-(l-azetidinyl)-2-pyridyl, 4-(l-fluoroethyl)-2-pyridyl, 4-(l-hydroxyethyl)-2-pyridyl, 4-(l,l-difluoroethyl)-2-pyridyl, 4-(2-fluoroethoxy)-2-pyridyl, 4-(2-fluoroethoxy)-2-pyrimidinyl, 4-(2-fluoroethoxy)-6-methyl-2-pyrimidinyl, 4-(2-fluoroethyl)-2-pyrimidinyl, 4-(2-fluoroethyl)-6-methyl-2-pyrimidinyl, 4-(2-hydroxyethyl)-6-methyl-2-pyrimidinyl, 4-(difluoromethyl)-2-pyridyl, 4-(trifluoromethyl)-2-pyridyl, 4- (trifluoromethyl)- 2-pyrimidinyl, 4-[(l-azetidinyl)carbonyl]-2-pyridyl. 4-aza-5-indanyl, 4-biphenylyl, 4-chloro-3-fluorophenyl, 4-chloro-5-fluoro-2-pyridyl. 4-chloro-5-methoxy-2-pyridyl, 4-chloro-5-methyl-2-pyridyl, 4-chloro-6-methyl-2-pyridyl, 4-cyclopropyl-2-pyridyl, 4-cyclopropyl-2-pyrimidinyl, 4-difluoromethoxy-2-pyridyl, 4-ethyl-2-pyridyl. 4-ethyl-6-(fluoromethyl)-2-pyridyl. 4-ethynyl-2-pyridyl, 4-fluoro-3 -tolyl, 4-fluoro-5-methyl-2-pyridyl, 4-fluoro-6-methyl-2-pyridyl, 4-fluorophenyl, 4-isopropyl-2-pyridyl, 4-isoquinolyl, 4-methoxy-2-pyridyl, 4-methoxy-2-pyrimidinyl, 4-methoxy-5-(trifluoromethyl)-2-pyridyl, 4-methoxy-5-methyl-2-pyridyl, 4-methoxy-6-methyl-2-pyridyl, 4-methoxy-6-methyl-2-pyrimidinyl, 4-methyl-l,3-benzothiazol-2-yl, 4-methyl-l,3,3a-triaza-2-indenyl, 4-methyl-2-pyridyl. 4-methyl-2-pyrimidinyl, 4-methyl-6-(trifluoromethyl)-2-pyrimidinyl, 4-methyl-6-quinolyl, 4-methyl-7-quinolyl, 4-quinolyl, 4,5-dichloro-2-pyridyl, 4,5-dimethyl-l,3-thiazol-2-yl,Atty. Docket: UCSF-849WO4,5-dimethyl-2-furyl, 4,5-dimethyl-2-pyridyl, 4,5,6,7-tetrahydro-2,3a-diaza-l-indenyl, 4, 5,6,7-tetrahydro-2,3a-diaza-3-indenyl, 4,6-diaza-5-indanyl, 4,6-dimethyl-2-pyridyl, 4,6-dimethyl-2-pyrimidinyl, 5-(l-azetidinyl)-2-pyridyl, 5-(l,l-difluoroethyl)-2-pyridyl. 5-(difluoromethyl)-4-methyl-2-pyridyl, 5-chloro-2-pyridyl, 5-chloro-4-methoxy-2-pyridyl, 5-chloro-4-methyl-2-pyridyl, 5-chloro-6-methoxy-2-pyridyl, 5-chloro-6-methyl-2-pyridyl, 5-cyclopropyl-2-pyridyl, 5-cyclopropyl- 3 -pyridyl, 5-cyclopropyl-4-methoxy-2-pyridyl, 5-difluoromethoxy-2-pyridyl, 5-fluoro-l,3a-diaza-2-indenyl, 5-fluoro-2-methyl-4-pyrimidinyl, 5-fluoro-4-methoxy-2-pyridyl, 5-fluoro-4-methyl-2-pyridyl, 5-fluoro-6-methyl-2-pyridyl, 5-isoquinolyl, 5-methoxy-2-pyrazinyl, 5-methoxy-2-pyridyl, 5-methoxy-2-pyrimidinyl, 5-methoxy-4-methyl-2-pyridyl, 5-methoxy-6-methyl-2-pyridyl, 5-methyl-l,3a-diaza-2-indenyl, 5-methyl-l,4,7a-triaza-3-indenyl, 5-methyl-2-pyrazinyl, 5-methyl-2-pyridyl, 5-methyl-2-pyrimidinyl, 5-methyl-2-quinolyl. 5-methyl-3-pyridyl, 5-methyl-3-quinolyl, 5-quinolyl, 5,6-dimethyl-2-pyridyl, 5,6-dimethyl-3-pyridyl, 5,7-dihydro-4H-6-oxa- 1,3a-diazainden-2-yl, 6-( 1, 1 -difluoroethyl)-2-pyridyl, 6-(2-fluoroethoxy)-2-pyridyl, 6-(fluoromethyl)-2-pyridyl, 6-(fluoromethyl)-4-methyl-2-pyridyl, 6-(hydroxymethyl)-2-pyridyl, 6-(hydroxymethyl)-4-methyl-2-pyridyl, 6-(trifluoromethyl)-2-pyridyl, 6-chloro- 1,3a-diaza-2-indenyl, 6-chloro- l,7a-diaza-2-indenyl, 6-chloro-3-quinolyl, 6-chloro-4-methyl-2-pyridyl, 6-chloro-5-methyl-2-pyridyl, 6-cinnolinyl, 6-cyano-2-pyridyl, 6-cyclopropyl-2-methyl-4-pyrimidinyl, 6-cyclopropyl-2-pyrazinyl, 6-cyclopropyl-2-pyridyl, 6-cyclopropyl-4-methyl-2-pyridyl, 6-cyclopropyl-4-pyrimidinyl, 6-ethyl-4-methyl-2-pyridyl, 6-ethyl-4-pyrimidinyl, 6-ethynyl-2-pyridyl, 6-ethynyl-4-pyrimidinyl, 6-fluoro-2-quinolyl, 6-fluoro-3 -quinolyl, 6-fluoro-4-(fluoromethyl)-2-pyridyl, 6-fluoro-4-methyl-2-pyridyl, 6-fluoro-5-(hydroxymethyl)-2-pyridyl, 6-fluoro-5-methyl-2-pyridyl, 6-isoquinolyl, 6-methoxy-2-pyridyl, 6-methoxy-3-pyridyl, 6-methoxy-4-methyl-2-pyridyl, 6-methoxy-5-methyl-2-pyridyl, 6-methoxy-5-methyl-3-pyridyl, 6-methyl- 1,3a-diaza-2-indenyl, 6-methyl- 1,3a-diaza-3-indenyl, 6-methyl- 1,4,7a-triaza-3-indenyl, 6-methyl-2-pyrazinyl, 6-methyl-2-pyridyl. 6-methyl-2-quinolyl. 6-methyl-3-pyridyl. 6-methyl-3-quinolyl, 6-methyl-4-(trifluoromethyl)-2-pyridyl, 6-methyl-4-nitro-2-pyridyl, 6-methyl-4-pyrimidinyl, 6-quinolyl, 6,7-dihydro-4H-5-oxa-l,7a-diazainden-2-yl, 6,7-dihydro-5H-4-oxa-l,7a-diazainden-3-yl, 7-(trifluoromethyl)-3-quinolyl, 7-fluoro-2,3-dihydro-l-benzofuran-6-yl, 7-fluoro-3-quinolyl, 7-methoxy-3-quinolyl, 7-methyl-l,3,3a-triaza-2-indenyl, 7-methyl-l,3a-diaza-2-indenyl, 7-methyl-l,3a-diaza-3-indenyl, 7-methyl-l,3a-diaza-5-indenyl, 7-methyl- 1,4,7 a-triaza-3-indenyl, 7-methyl-l,7a-diaza-3-indenyl, 7-methyl-3-quinolyl, 7 -quinolyl, 8-chloro-3-Atty. Docket: UCSF-849WOquinolyl, 8-fluoro-3-quinolyl, 8-fluoro-6-isoquinolyl, 8-isoquinolyl, 8-methoxy-3-quinolyl, 8-methyl-3-quinolyl, 8-methyl-6-isoquinolyl, 8-methyl-6-quinolyl, 8-quinolyl, m-chlorophenyl, m-fluorophenyl, or m-tolyl.Groups T & X:

[0092] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (V):wherein Z is as defined herein.

[0093] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (VI):Atty. Docket: UCSF-849WO

[0094] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (VII):wherein Z is as defined herein.

[0095] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (Vila):wherein Z is as defined herein.

[0096] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (Vllb):wherein Z is as defined herein.Atty. Docket: UCSF-849WO

[0097] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (Vile):wherein Z is as defined herein.

[0098] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (VIII):CF3(VIII)wherein Z is as defined herein.

[0099] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (IX):Atty. Docket: UCSF-849WO

[0100] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (X):

[0101] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (Xa):

[0102] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (Xb):wherein Z is as defined herein.Atty. Docket: UCSF-849WO

[0103] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (Xc):wherein Z is as defined herein.

[0104] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (XI):wherein Z is as defined herein.

[0105] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (XII):wherein Z is as defined herein.Atty. Docket: UCSF-849WO

[0106] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (XIII):wherein Z is as defined herein.

[0107] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (Xllla):wherein Z is as defined herein.

[0108] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (Xlllb):wherein Z is as defined herein.Atty. Docket: UCSF-849WO

[0109] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (XIIIc):wherein Z is as defined herein.Groups X & Z:

[0110] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (XIV):ZCF3 (XIV)wherein T is as defined herein, and Z is l-methylisoquinolin-6-yl, 2-(trifluoromethyl)pyrimidin- 4-yl, 2-methylpyrimidin-4-yl, l-methyl-6-isoquinolyl, l-(2-hydroxyethyl)-6-isoquinolyl, 3-isoquinolyl, 6-quinolyl, 8-fluoro-3-quinolyl, 8-fluoro-7-quinolyl, 4-methyl-l,7a-diaza-2-indenyl, l-thia-5-aza-2-indenyl, l-(2-fluoroethyl)-lH-indazol-5-yl, 3-quinolyl, 2-cyclopropyl-2H-indazol- 5-yl, 6-fluoro-l,3-benzoxazol-2-yl, 5-fluoro-2-pyridyl, l-benzofuran-2-yl, or phenyl.Atty. Docket: UCSF-849WO

[0111] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (XV):wherein T is as defined herein, and Z is l-methylisoquinolin-6-yl, 2-(trifluoromethyl)pyrimidin- 4-yl, 2-methylpyrimidin-4-yl, l-methyl-6-isoquinolyl, l-(2-hydroxyethyl)-6-isoquinolyl, 3-isoquinolyl, 6-quinolyl, 8-fluoro-3-quinolyl, 8-fluoro-7-quinolyl, 4-methyl-l,7a-diaza-2-indenyl, l-thia-5-aza-2-indenyl, l-(2-fluoroethyl)-lH-indazol-5-yl, 3-quinolyl, 2-cyclopropyl-2H-indazol- 5-yl, 6-fluoro-l,3-benzoxazol-2-yl, 5-fluoro-2-pyridyl, l-benzofuran-2-yl, or phenyl.

[0112] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (XVI):wherein T is as defined herein, and Z is l-methylisoquinolin-6-yl, 2-(trifluoromethyl)pyrimidin- 4-yl, 2-methylpyrimidin-4-yl, l-methyl-6-isoquinolyl, l-(2-hydroxyethyl)-6-isoquinolyl, 3-isoquinolyl, 6-quinolyl, 8-fluoro-3-quinolyl. 8-fluoro-7-quinolyl, 4-methyl-l,7a-diaza-2-indenyl, l-thia-5-aza-2-indenyl, l-(2-fluoroethyl)-lH-indazol-5-yl, 3-quinolyl, 2-cyclopropyl-2H-indazol- 5-yl, 6-fluoro-l,3-benzoxazol-2-yl, 5-fluoro-2-pyridyl, l-benzofuran-2-yl, or phenyl.Atty. Docket: UCSF-849WOGroups T & Z:

[0113] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (XVII):wherein X is as defined herein, and Z is l-methylisoquinolin-6-yl, 2-(trifluoromethyl)pyrimidin- 4-yl, 2-methylpyrimidin-4-yl, l-methyl-6-isoquinolyl, l-(2-hydroxyethyl)-6-isoquinolyl, 3-isoquinolyl, 6-quinolyl, 8-fluoro-3-quinolyl, 8-fluoro-7-quinolyl, 4-methyl-l,7a-diaza-2-indenyl, l-thia-5-aza-2-indenyl, l-(2-fluoroethyl)-lH-indazol-5-yl, 3-quinolyl, 2-cyclopropyl-2H-indazol- 5-yl, 6-fluoro-l,3-benzoxazol-2-yl, 5-fluoro-2-pyridyl, l-benzofuran-2-yl, or phenyl.

[0114] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (XVIII):zX(XVIII)wherein X is as defined herein, and Z is l-methylisoquinolin-6-yl. 2-(trifluoromethyl) pyrimidin- 4-yl, 2-methylpyrimidin-4-yl, l-methyl-6-isoquinolyl, l-(2-hydroxyethyl)-6-isoquinolyl, 3-isoquinolyl, 6-quinolyl, 8-fluoro-3-quinolyl, 8-fluoro-7-quinolyl, 4-methyl-l,7a-diaza-2-indenyl, l-thia-5-aza-2-indenyl, l-(2-fluoroethyl)-lH-indazol-5-yl, 3-quinolyl, 2-cyclopropyl-2H-indazol- 5-yl, 6-fluoro-l,3-benzoxazol-2-yl, 5-fluoro-2-pyridyl, l-benzofuran-2-yl, or phenyl.Atty. Docket: UCSF-849WO

[0115] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, has a structure according to formula (XIX):ZO \ / N \X / F(XIX)wherein X is as defined herein, and Z is l-methylisoquinolin-6-yl, 2-(trifluoromethyl) pyrimidin- 4-yl, 2-methylpyrimidin-4-yl, l-methyl-6-isoquinolyl, l-(2-hydroxyethyl)-6-isoquinolyl, 3-isoquinolyl, 6-quinolyl, 8-fluoro-3-quinolyl. 8-fluoro-7-quinolyl, 4-methyl-l,7a-diaza-2-indenyl, l-thia-5-aza-2-indenyl, l-(2-fluoroethyl)-lH-indazol-5-yl, 3-quinolyl, 2-cyclopropyl-2H-indazol- 5-yl, 6-fluoro-l,3-benzoxazol-2-yl, 5-fluoro-2-pyridyl, l-benzofuran-2-yl, or phenyl.

[0116] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is 4-cyclopropyl-I-[5-(p-fluorophenyl)-2-(I-methyl-6-isoquinolyl)-l,3-oxazol-4-yl]-2(IH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is 4-cyclopropyl-l-{2-(l-methyl-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is 4-cyclopropyl-l-{2-[6-(fluoromethyl)-5-methyl-2-pyridyl]-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is l-(5-(4-chloro-3-fluorophenyl)-2-(6-(fluoromethyl)-4-methylpyridin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is 4-cyclopropyl-l-[2-(6-fluoro-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is l-[5-(4-chloro-3-fluorophenyl)-2-(6-fluoro-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is l-(5-Atty. Docket: UCSF-849WO(4-chloro-3-fluorophenyl)-2-(5,7-dimethylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is l-(5-(4-chloro-3-fluorophenyl)-2-(l-methyl-lH-pyrazolo[4,3-b]pyridin-3-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is 4-cyclopropyl-l-(5-(4-fluorophenyl)-2-(l-methyl-lH-indazol-5-yl)oxazol-4-yl)pyrimidin-2(lH)-one, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is l-[2-(m-chlorophenyl)-5-(p-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof.

[0117] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 1: l-[5-(4-chloro-3-fluorophenyl)-2-( 1 -methyl- lH-indazol-5-yl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 2: l-[5-(4-chloro-3-fluorophenyl)-2-(m-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2( lH)-pyrimidinone, 3: 1 - [5-(3-chloro-4-fluorophenyl)-2-(m-tolyl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2(lH)-pyrimidinone, 4: l-[5-(4-chloro-3-fluorophenyl)-2-(2-methyl-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 5: l-[5-(4-chloro-3-fluorophenyl)-2-(4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 6: l-[5-(4-chloro-3-fluorophenyl)-2-(5-methyl-3-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 7: 1-[5-(4-chloro-3-fluorophenyl)-2-(2-methyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 8: l-[5-(4-chloro-3-fluorophenyl)-2-(6-methyl-2-pyrazinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 9: l-[5-(4-chloro-3-fluorophenyl)-2-(3,5-xylyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 10: l-[5-(4-chloro-3-fluorophenyl)-2-(5,6-dimethyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 11: l-[5-(4-chloro-3-fluorophenyl)-2-(4,6-dimethyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 12: l-[5-(4-chloro-3-fluorophenyl)-2-(2-ethyl-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 13: l-[5-(4-chloro-3-fluorophenyl)-2-(4-ethyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 14: l-[5-(4-chloro-3-fluorophenyl)-2-(2,6-dimethyl-4-pyrimidinyl)-1,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 15: l-[5-(4-chloro-3-fluorophenyl)-2-(4,6-dimethyl-2-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 16: l-[5-(4-chloro-3-fluorophenyl)-2-(6-methoxy-2-pyridyl)-l,3-oxazol-4-yl]-4-Atty. Docket: UCSF-849WOcyclopropyl-2(lH)-pyrimidinone, 17: l-[5-(4-chloro-3-fluorophenyl)-2-(2-methoxy-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 18: l-[5-(4-chloro-3-fluorophenyl)-2-(2-fluoro-5-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 19: l-[5-(4-chloro-3-fluorophenyl)-2-(4-fluoro-3-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, and 20: l-[5-(4-chloro-3-fluorophenyl)-2-(2-fluoro-3-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0118] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 21: l-[5-(4-chloro-3-fluorophenyl)-2-(3-fluoro-5-tolyl)- 1,3-oxazol-4-yl]-4-cyclopropyl-2(l H)-pyrimidinone, 22: 1 -[5-(4-chloro-3-fluorophenyl)-2-(2-methoxy-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 23: l-[5-(4-chloro-3-fluorophenyl)-2-(6-fluoro-5-methyl-2-pyridyl)-l,3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 24: 1 - [5-(4-chloro-3-fluorophenyl)-2-(6-fluoro-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 25: l-[5-(4-chloro-3-fluorophenyl)-2-(3-fluoro-6-methyl-2-pyridyl)-1.3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 26: l-[5-(4-chloro-3-fluorophenyl)-2-(4-fluoro-6-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 27: l-[5-(4-chloro-3-fluorophenyl)-2-(5-fluoro-6-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 28: l-[5-(4-chloro-3-fluorophenyl)-2-(m-chlorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 29: 1-[5-(4-chloro-3-fhiorophenyl)-2-(5-chloro-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 30: l-[2-(l,7a-diaza-2-indenyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 31: l-[2-(l,3a-diaza-6-indenyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 32: l-[2-(l,7a-diaza-6-indenyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 33: l-[5-(4-chloro- 3-fluorophenyl)-2-(6-cyclopropyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 34: l-[2-(l,4,7a-triaza-5-indenyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-ylJ- 4-cyclopropyl-2(lH)-pyrimidinone, 35: l-[2-(l,4,7a-triaza-3-indenyl)-5-(4-chloro-3-fhiorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 36: l-[2-(l,4,7a-triaza-6-indenyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 37: l-[5-(4-chloro-3-fluorophenyl)-2-(l-oxa-4-aza-2-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 38: l-[2-(l,3a,4-triaza-2-indenyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-Atty. Docket: UCSF-849WO4-yl]-4-cyclopropyl-2(1H)-pyrimidinone, 39: l-[2-(l,3,3a-triaza-6-indenyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, and 40: l-[2-(l,3a,4-triaza- 3-indenyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0119] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 41: l-[2-(l,4,7a-triaza-2-indenyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 42: l-[5-(4-chloro-3-fluorophenyl)-2-(2-cyclopropyl-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 43: l-[5-(4-chloro-3-fluorophenyl)-2-(4-cyclopropyl-2-pyridyl)-1,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 44: l-[2-(4-aza-5-indanyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 45: l-[5-(4-chloro-3-fluorophenyl)-2-(5-cyclopropyl-3-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 46: l-[5-(4-chloro-3-fluorophenyl)-2-(2-cyclopropyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 47: l-[5-(4-chloro-3-fluorophenyl)-2-(2,3-dihydro-l-benzofuran-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 48: l-[5-(4-chloro-3-fluorophenyl)-2-(2,3-dihydro-l-benzofuran-4-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 49: l-[5-(4-chloro-3-fluorophenyl)-2-(2-isopropyl-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 50: l-[5-(4-chloro-3-fluorophenyl)-2-(l-oxa-7-aza-5-indanyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 51: l-[5-(4-chloro-3-fluorophenyl)-2-(2-chloro-6-methyl-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 52: l-[5-(4-chloro-3-fluorophenyl)-2-(6-chloro-5-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 53: l-[5-(4-chloro-3-fluorophenyl)-2-(5-chloro-6-methyl-2-pyridyl)-l,3-oxazol- 4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 54: l-[5-(4-chloro-3-fluorophenyl)-2-(6-chloro-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 55: l-[5-(4-chloro-3-fhiorophenyl)-2-(2-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 56: l-[5-(4-chloro-3-fluorophenyl)-2-(7-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 57: l-[5-(4-chloro-3-fluorophenyl)-2-(6-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 58: 1 -{5-(4-chloro-3-fluorophenyl)-2-[2-(difluoromethyl)-4-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 59: l-[5-(4-chloro-3-fluorophenyl)-2-(6-isoquinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, and 60: l-[5-(4-chloro-3-fluorophenyl)-2-Atty. Docket: UCSF-849WO(3-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0120] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 61: l-[5-(4-chloro-3-fluorophenyl)-2-(2-quinoxalinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 62: l-[5-(4-chloro-3-fluorophenyl)-2-(l-methyl-lH-l,4-diazainden-3-yl)-l,3-oxazol-4-ylJ-4-cyclopropyl-2(lH)-pyrimidinone, 63: l-[5-(4-chloro-3-fluorophenyl)-2-(2-methyl-l,3a-diaza-5-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 64: l-[5-(4-chloro-3-fluorophenyl)-2-(6-methyl-l,3a-diaza-3-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 65: l-[5-(4-chloro-3-fluorophenyl)-2-(l-methyl-lH-l,6-diazainden-3-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 66: l-[5-(4-chloro-3-fluorophenyl)-2-(3-methyl-l,3a-diaza-5-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 67: l-[5-(4-chloro-3-fluorophenyl)-2-(7-methyl-l,3a-diaza-5-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 68: l-[5-(4-chloro-3-fluorophenyl)-2-(3-methyl-l,3a-diaza-6-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 69: l-[5-(4-chloro-3-fhiorophenyl)-2-(l-methyl-lH-l,4-diazainden-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 70: l-[5-(4-chloro-3-fluorophenyl)-2-(6-cyclopropyl-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 71: l-[5-(4-chloro-3-fluorophenyl)-2-(l -methyl- 1H-1, 2, 7-triazainden-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 72: l-[5-(4-chloro-3-fluorophenyl)-2-(l-methyl-lH-l,2,6-triazainden-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 73: l-[5-(4-chloro-3-fluorophenyl)-2-(l-methyl-lH-l,2,3-benzotriazol-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 74: l-[5-(4-chloro-3-fluorophenyl)-2-(7-methyl-l,4,7a-triaza-3-indenyl)-l,3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 75: 1 - [5-(4-chloro-3-fluorophenyl)-2-(5-methyl- 1,4,7 a-triaza-3-indenyl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2 ( 1 H)-pyrimidinone, 76: 1 - [5-(4-chloro-3-fluorophenyl)-2-( 1 -methyl- 1 H- 1,2,6-triazainden-3-yl)- 1,3-oxazol-4-ylJ -4-cyclopropyl-2(lH)-pyrimidinone, 77: l-[5-(4-chloro-3-fluorophenyl)-2-(2-methyl-l,3-benzoxazol-6-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 78: l-[5-(4-chloro-3-fluorophenyl)-2-(l -methyl- 1H-1, 2, 5-triazainden-3-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 79: l-[5-(4-chloro-3-fhiorophenyl)-2-(l-methyl-lH-l,2,7-triazainden-3-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, and 80: l-[5-(4-chloro-3-fluorophenyl)-2-(5-Atty. Docket: UCSF-849WOfluoro-l,3a-diaza-2-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0121] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 81: l-[5-(4-chloro-3-fluorophenyl)-2-(6-methyl-4-nitro-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 82: l-[5-(4-chloro-3-fluorophenyl)-2-(l-methyl-6-isoquinolyl)-l,3-oxazol-4-ylJ-4-cyclopropyl-2(lH)-pyrimidinone, 83: l-[5-(4-chloro-3-fluorophenyl)-2-(2-methyl-6-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 84: l-[5-(4-chloro-3-fluorophenyl)-2-(2-methyl-7-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 85: l-[5-(4-chloro-3-fluorophenyl)-2-(3-methyl-6-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 86: l-[5-(4-chloro-3-fluorophenyl)-2-(4-methyl-6-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 87: l-[5-(4-chloro-3-fluorophenyl)-2-(8-methyl-6-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 88: l-{5-(4-chloro-3-fluorophenyl)-2-[6-(l,l-difluoroethyl)-2-pyridyl] - 1,3-oxazol-4-yl } -4-cyclopropyl-2( 1 H)-pyrimidinone. 89: 1 -[5-(4-chloro-3-fluorophenyl)-2-(4-methyl-7-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 90: l-[5-(4-chloro-3-fluorophenyl)-2-(2-difluoromethoxy-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 91: l-[5-(4-chloro-3-fluorophenyl)-2-(l-methyl-3-methyl-lH-indazol-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 92: l-{5-(4-chloro-3-fluorophenyl)-2-[6-(trifhioromethyl)-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 93: l-{ 5-(4-chloro-3-fluorophenyl)-2-[4-(trifluoromethyl)-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 94: l-[5-(4-chloro-3-fluorophenyl)-2-(6-fluoro-2-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 95: l-[5-(4-chloro-3-fluorophenyl)-2-(2,6-dichloro-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 96: l-[5-(4-chloro-3-fluorophenyl)-2-(2-fluoro-6-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 97: l-{5-(4-chloro-3-fluorophenyl)-2-[2-(trifluoromethyl)-4-pyrimidinylJ-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 98: l-[5-(4-chloro-3-fluorophenyl)-2-(l-cyclopropyl-lH-indazol-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 99: l-[5-(4-chloro-3-fluorophenyl)-2-(3-cyclopropyl-l,4,7a-triaza-6-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, and 100: l-[5-(4-chloro-3-fluorophenyl)-2-(7-methoxy-3-quinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt orAtty. Docket: UCSF-849WOa hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0122] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 101: l-{5-(4-chloro-3-fluorophenyl)-2-[6-methyl-4-(trifluoromethyl)-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 102: l-{5-(4-chloro-3-fluorophenyl)-2-[2-(trifluoromethyl)-6-quinolyl]-l,3-oxazol-4-yl } -4-cyclopropyl-2( 1 H)-pyrimidinone, 103: 1 - [5-(4-chloro-3-fluorophenyl)-2-( 1 -methyl-l,5-diaza-6-indanyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 104: l-[5-(4-chloro-3-fluorophenyl)-2-(6-methyl-3-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 105: l-[5-(4-chloro-3-fluorophenyl)-2-(4,5-dimethyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 106: l-[5-(4-chloro-3-fluorophenyl)-2-(l-cyclopropyl-4-pyrazolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 107: l-[5-(4-chloro-3-fluorophenyl)-2-(5-methoxy-2-pyrazinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 108: l-[5-(4-chloro-3-fluorophenyl)-2-(5-fluoro-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 109: 2-[5-(4-chloro-3-fluorophenyl)-4-(4-cyclopropyl-2-oxo- 1-pyrimidinyl)-l,3-oxazol-2-yl]isonicotinamide, 110: l-[5-(4-chloro-3-fluorophenyl)-2-(4-methoxy-5-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 111: l-{ 5-(4-chloro-3-fluorophenyl)-2-[6-(hydroxymethyl)-4-methyl-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 112: l-[5-(4-chloro-3-fluorophenyl)-2-(5-methoxy-4-methyl- 2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 113: l-{5-(4-chloro-3-fluorophenyl)-2-[6-(fluoromethyl)-4-methyl-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 114: l-[5-(4-chloro-3-fluorophenyl)-2-(3,4-dihydro-2H-l-oxa-7-azanaphth-6-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 115: l-{5-(4-chloro-3-fluorophenyl)-2-[4-(2-hydroxyethyl)-6-methyl-2-pyrimidinyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 116: l-{5-(4-chloro-3-fluorophenyl)-2-[4-(2-fluoroethyl)-6-methyl-2-pyrimidinyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 117: l-{5-(4-chloro-3-fluorophenyl)-2-[4-(2-fluoroethoxy)-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 118: l-[5-(4-chloro-3-fluorophenyl)-2-(3,3-difluoro-4-aza-5-indanyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 119: 1 -[5-(4-chloro-3-fluorophenyl)-2-(3,3-difluoro-5-aza-6-indanyl)- 1,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, and 120: l-[5-(4-chloro-3-fluorophenyl)-2-(l,l-difluoro-4-aza-5-indanyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplaryAtty. Docket: UCSF-849WOembodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0123] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 121: l-[5-(4-chloro-3-fluorophenyl)-2-(6-ethyl-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 122: l-[5-(4-chloro-3-fluorophenyl)-2-(2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2( 1 H)-pyrimidinone, 123: 1 -[5-(4-chloro-3-fluorophenyl)-2-( 1 -methyl-4-pyrazolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 124: l-[5-(4-chloro-3-fluorophenyl)-2-(5-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 125: l-[5-(4-chloro-3-fluorophenyl)-2-(4-methyl-2-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 126: l-[5-(4-chloro-3-fluorophenyl)-2-(5-methyl-2-pyrazinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 127: l-[5-(4-chloro-3-fluorophenyl)-2-(l-methyl-5-methyl-3-pyrazolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 128: l-[5-(4-chloro-3-fluorophenyl)-2-(l-methyl-4-methyl-3-pyrazolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 129: l-[5-(4-chloro-3-fluorophenyl)-2-(2-methyl-l,3-thiazol-4-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 130: l-[5-(4-chloro-3-fluorophenyl)-2-(4-ethynyl-2-pyridyl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2( lH)-pyrimidinone, 131: 1 - [5-(4-chloro-3-fluorophenyl)-2-(2,6-dimethyl-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 132: l-[5-(4-chloro-3-fluorophenyl)-2-(5,6-dimethyl-3-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 133: l-[5-(4-chloro-3-fluorophenyl)-2-(2-ethyl-4-pyrimidinyl)-l,3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 134: 1 - { 5-(4-chloro-3-fluorophenyl)-2-( 1,2-diazabicyclo[3.3.0]octa-2,4-dien-3-yl)-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 135: l-[5-(4-chloro-3-fluorophenyl)-2-(4-methoxy-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 136: l-[5-(4-chloro-3-fluorophenyl)-2-(6-methoxy-3-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 137: l-{5-(4-chloro-3-fluorophenyl)-2-[6-(hydroxymethyl)-2-pyridyl]-1,3-oxazol-4-yl}-4-cyclopropyl-2(1H)-pyrimidinone, 138: l-[5-(4-chloro-3-fluorophenyl)-2-(5-methoxy-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 139: l-[5-(4-chloro-3-fluorophenyl)-2-(4-methoxy-2-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, and 140: l-[5-(4-chloro-3-fluorophenyl)-2-(5-methoxy-2-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplaryAtty. Docket: UCSF-849WOembodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0124] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 141: l-[5-(4-chloro-3-fluorophenyl)-2-(2-fluoro-6-methyl-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 142: l-{5-(4-chloro-3-fluorophenyl)-2-[6-(fluoromethyl)-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 143: l-[5-(4-chloro-3-fluorophenyl)-2-(4-fluoro-5-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 144: l-[5-(4-chloro-3-fluorophenyl)-2-(4-fluoro-5-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 145: l-[5-(4-chloro-3-fluorophenyl)-2-(5-fluoro-2-methyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 146: l-[5-(4-chloro-3-fluorophenyl)-2-(2-chloro-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 147: l-{5-(4-chloro-3-fluorophenyl)-2- [2-( 1 -propynyl)-4-pyridyl] - 1,3-oxazol-4-yl } -4-cyclopropyl-2( lH)-pyrimidinone, 148: l-[5-(4-chloro-3-fluorophenyl)-2-(l-oxa-5-aza-6-indenyl)-1.3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 149: l-[5-(4-chloro-3-fluorophenyl)-2-(5-cyclopropyl-2-pyridyl)-1.3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 150: 1 - [5-(4-chloro-3-fluorophenyl)-2-(4,6-diaza-5-indanyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 151: l-[5-(4-chloro-3-fluorophenyl)-2-(6-cyclopropyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 152: 1 - [5- (4-chl oro-3 -flu orophenyl)-2-(6-cyclopropyl-2-pyrazinyl)- 1,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 153: l-[5-(4-chloro-3-fluorophenyl)-2-(l-oxa-7-aza-6-indanyl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 154: l-[5-(4-chloro-3-fluorophenyl)-2-(l-oxa-6-aza-5-indanyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 155: l-[5-(4-chloro-3-fluorophenyl)-2-(4-isopropyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 156: l-[5-(4-chloro-3-fluorophenyl)-2-(4,5,6,7-tetrahydro-2,3a-diaza-l-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 157: l-[5-(4-chloro-3-fluorophenyl)-2-(4,5,6,7-tetrahydro-2,3a-diaza-3-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2( lH)-pyrimidinone, 158: 1 - [5-(4-chloro-3-fluorophenyl)-2-(6-methoxy-5-methyl-3-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 159: 1-{5-(4-chloro-3-fluorophenyl)-2-[4-(1-hydroxyethyl)-2-pyridyl]-1,3-oxazol-4-yl}-4-cyclopropyl-2(1H)-pyrimidinone, and 160: 1-[5-(4-chloro-3-fluorophenyl)-2-(4-methoxy-6-methyl-2-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or aAtty. Docket: UCSF-849WOhydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0125] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 161: l-[5-(4-chloro-3-fluorophenyl)-2-(2-cyclopropyl-l,3-thiazol-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 162: 1 - [5- (4-chloro-3 -fluorophenyl)-2-(2-cyclopropyl- 1,3-thiazol-4-yl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 163: 1 - [5- (4-chloro-3-fluorophenyl)-2- (2-ethyl-5-fluoro-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 164: 1- { 5-(4-chloro-3-fluorophenyl)-2-[6-fluoro-5-(hydroxymethyl)-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 165: l-[5-(4-chloro-3-fluorophenyl)-2-(5-fluoro-4-methoxy-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 166: l-[5-(4-chloro-3-fluorophenyl)-2-(3-chloro-6-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 167: l-[5-(4-chloro-3-fluorophenyl)-2-(4-chloro-6-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 168: 1-[5-(4-chloro-3-fluorophenyl)-2-(4-chloro-5-methyl-2-pyridyl)-1,3-oxazol-4-yl]-4-cyclopropyl-2(1H)-pyrimidinone, 169: l-[5-(4-chloro-3-fluorophenyl)-2-(5-chloro-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 170: l-{5-(4-chloro-3-fluorophenyl)-2-[4-(difluoromethyl)-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 171: l-[5-(4-chloro-3-fluorophenyl)-2-(5-isoquinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 172: 1-[5-(4-chloro-3-fluorophenyl)-2-(8-quinolyl)-1,3-oxazol-4-yl]-4-cyclopropyl-2(1H)-pyrimidinone, 173: l-[5-(4-chloro-3-fluorophenyl)-2-(2-chloro-3-fluoro-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 174: l-[5-(4-chloro-3-fluorophenyl)-2-(4-chloro-5-fluoro-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 175: l-[5-(4-chloro-3-fluorophenyl)-2-(3-oxo-4-aza-5-indanyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 176: l-{5-(4-chloro-3-fluorophenyl)-2-[2-(l-methylcyclopropyl)-4-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 177: 1-[5-(4-chloro-3-fluorophenyl)-2-(2-cyclobutyl-4-pyridyl)-1,3-oxazol-4-yl]-4-cyclopropyl-2(1H)-pyrimidinone, 178: l-[5-(4-chloro-3-fluorophenyl)-2-(6-cyclopropyl-2-methyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 179: l-{2-[6-(l-azetidinyl)-2-pyridyl]-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, and 180: l-{2-[5-(l-azetidinyl)-2-pyridyl]-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound,Atty. Docket: UCSF-849WOor a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0126] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 181: 1-[5-(4-chloro-3-fluorophenyl)-2-(1-methyl-1,6-diaza-5-indanyl)-1,3-oxazol-4-yl]-4-cyclopropyl-2(1H)-pyrimidinone, 182: l-[5-(4-chloro-3-fluorophenyl)-2-(2-cyclopropoxy-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 183: l-[5-(4-chloro-3-fluorophenyl)-2-(2-cyclopropyl-5-fluoro-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 184: l-{5-(4-chloro- 3-fluorophenyl)-2-[4-ethyl-6-(fluoromethyl)-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 185: l-{5-(4-chloro-3-fluorophenyl)-2-[6-(2-fluoroethoxy)-2-pyridyl]-l,3-oxazol- 4-yl } -4-cyclopropyl-2( lH)-pyrimidinone, 186: 1 - { 5-(4-chloro-3-fluorophenyl)-2-[4-( 1, 1 -difluoroethyl)-2-pyridyl] - 1,3-oxazol-4-yl }-4-cyclopropyl-2( lH)-pyrimidinone. 187: 1 - { 5- (4-chloro-3-fluorophenyl)-2-[5-(difluoromethyl)-4-methyl-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(l H)-pyrimidinone, 188: 1 - { 5-(4-chloro-3-fluorophenyl)-2- [5-( 1, 1 -difluoroethyl)-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone. 189: l-{5-(4-chloro-3-fluorophenyl)-2-[2-(2-cyclopropylethynyl)-4-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 190: 1 - [5- (4-chloro-3 -fluorophenyl)-2-(5-chloro-4-methoxy-2-pyridyl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 191: 1 - [5-(4-chloro-3-fluorophenyl)-2-(4-chloro-5-methoxy-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 192: l-[5-(4-chloro-3-fluorophenyl)-2-(4-difluoromethoxy-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 193: l-[5-(4-chloro-3-fluorophenyl)-2-(5-difluoromethoxy-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 194: l-{5-(4-chloro-3-fluorophenyl)-2-[2- ( triflu oromethyl)-4-pyridyl]- 1,3-oxazol-4-yl } -4-cyclopropyl-2( 1 H)-pyrimidinone, 195: 1 - [5 -(4-chloro-3-fluorophenyl)-2-(4,5-dichloro-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 196: l-(2-{4-[(l-azetidinyl)carbonyl]-2-pyridyl}-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl)-4-cyclopropyl-2(lH)-pyrimidinone, 197: l-{5-(4-chloro-3-fluorophenyl)-2-[4-methoxy-5-(trifluoromethyl)-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 198: l-[5-(4-chloro-3-fluorophenyl)-2-(4-cyclopropyl-2-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2( 1 H)-pyrimidinone, 199: 1 -[5-(4-chloro-3-fluorophenyl)-2-(l -methyl- 1 H- 1,2,4-triazol-3-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, and 200: l-[5-(4-chloro-3-fluorophenyl)-2-(6-methyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone.Atty. Docket: UCSF-849WOIn an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0127] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 201: l-[5-(4-chloro-3-fluorophenyl)-2-(5-methyl-2-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 202: l-[5-(4-chloro-3-fluorophenyl)-2-(6-ethynyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 203: l-[2-(l,3a-diaza-2-indenyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 204: l-{5-(4-chloro-3-fluorophenyl)-2-[4-( 1 -fluoroethyl)-2-pyridyl]- 1,3-oxazol-4-yl } -4-cyclopropyl-2( lH)-pyrimidinone, 205: 1 - { 5- (4-chloro-3-fluorophenyl)-2-[4-(2-fluoroethyl)-2-pyrimidinyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 206: l-{5-(4-chloro-3-fluorophenyl)-2-[6-fluoro-4-(fluoromethyl)-2-pyridyl] - 1,3-oxazol-4-yl } -4-cyclopropyl-2( lH)-pyrimidinone, 207: l-[5-(4-chloro-3-fluorophenyl)-2-(7-methyl-l,3a-diaza-2-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 208: l-[5-(4-chloro-3-fluorophenyl)-2-(7-methyl-l,3a-diaza-3-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 209: l-[5-(4-chloro-3-fluorophenyl)-2-(5-methyl-l,3a-diaza-2-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 210: l-[5-(4-chloro-3-fluorophenyl)-2-(6-methyl-l,3a-diaza-2-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 211: 1-[5-(4-chloro-3-fluorophenyl)-2-(7-methyl-1,7a-diaza-3-indenyl)-1,3-oxazol-4-yl]-4-cyclopropyl-2(1H)-pyrimidinone, 212: l-[5-(4-chloro-3-fluorophenyl)-2-(4-methyl- 1,3,3a-triaza-2-indenyl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2 ( 1 H)-pyrimidinone, 213: 1 - { 2-[4-(l-azetidinyl)-2-pyridyl]-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 214: l-{5-(4-chloro-3-fluorophenyl)-2-[4-(2-fluoroethoxy)-2-pyrimidinyl]-l,3-oxazol-4-yl } -4-cyclopropyl-2( 1 H)-pyrimidinone, 215: 1-{5-(4-chloro-3-fluorophenyl)-2-[4-(trifluoromethyl)-2-pyrimidinyl]-1,3-oxazol-4-yl}-4-cyclopropyl-2(1H)-pyrimidinone, 216: 1 -[2-(6-chloro-l,7a-diaza-2-indenyl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2( lH)-pyrimidinone, 217: 1-[2-(6-chloro-1,3a-diaza-2-indenyl)-5-(4-chloro-3-fluorophenyl)-1,3-oxazol-4-yl]-4-cyclopropyl-2(1H)-pyrimidinone, 218: 1 - { 5-(4-chloro-3-fluorophenyl)-2-[4-(2-fluoroethoxy)-6-methyl-2-pyrimidinyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 219: l-[5-(4-chloro-3-fluorophenyl)-2-(2-ethynyl-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, and 220: l-[5-(4-chloro-3-fluorophenyl)-2-(6-ethynyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound,Atty. Docket: UCSF-849WOor a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0128] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 221: l-[5-(4-chloro-3-fluorophenyl)-2-(2-ethynyl-5-fluoro-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 222: l-[5-(4-chloro-3-fluorophenyl)-2-(2-ethynyl-6-fluoro-4-pyridyl)-l,3-oxazol-4-ylJ-4-cyclopropyl-2(lH)-pyrimidinone, 223: l-[5-(4-chloro-3-fluorophenyl)-2-(2-methyl-l,3-thiazol-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 224: l-{5-(4-chloro-3-fluorophenyl)-2-(l,2-diazabicyclo[3.3.0]octa-2,4-dien-4-yl)-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 225: l-[5-(4-chloro-3-fluorophenyl)-2-(2-fluoro-6-vinyl-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 226: l-[5-(4-chloro-3-fluorophenyl)-2-(6,7-dihydro-5H-4-oxa-l,7a-diazainden-3-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 227: 4-cyclopropyl-l-{2-(l-methyl-2-oxo-6-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 228: 4-cyclopropyl- l-{2-(6-fluoro-5-methyl-2-pyridyl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 229: 4-cyclopropyl-1-{2-(5-fluoro-6-methyl-2-pyridyl)-5-[p-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}-2(1H)-pyrimidinone, 230: l-{2-(5-chloro-2-pyridyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 231: l-{2-(l,3a-diaza-6-indenyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl } -4-cyclopropyl-2( lH)-pyrimidinone, 232: 4-cyclopropyl-1-{2-(1-oxa-4-aza-2-indenyl)-5-[p-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}-2(1H)-pyrimidinone, 233: l-{2-(l,4,7a-triaza-3-indenyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, and 234: l-{2-(4-aza-5-indanyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}- 4-cyclopropyl-2(lH)-pyrimidinone, 235: 4-cyclopropyl-l-{2-(2,3-dihydro-l-benzofuran-5-yl)- 5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 236: l-{2-(5-chloro-6-methyl-2-pyridyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 237: l-{2-(6-chloro-5-methyl-2-pyridyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 238: 4-cyclopropyl- l-{2-(2-naphthyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 239: 4-cyclopropyl- l-{2-(l-naphthyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, and 240: 4-cyclopropyl- 1 - { 2-(6-quinolyl)-5-[p-(trifluoromethyl)phenyl]- 1,3-oxazol-4-yl } -2( 1H)-Atty. Docket: UCSF-849WOpyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0129] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 241: 4-cyclopropyl-l-{2-(7-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 242: 4-cyclopropyl-l-{2-(3-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 243: 4-cyclopropyl- l-{2-(2-quinolyl)-5-[p-(trifluoromethyl)phenylJ-l,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 244: 4-cyclopropyl- 1 - { 2-(8-quinolyl)-5- [p- (triflu oromethyl)phenyl] -l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 245: 4-cyclopropyl- l-{2-(5-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 246: 4-cyclopropyl- 1-{2-(5-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 247: 4-cyclopropyl- 1 - { 2-(4-isoquinolyl)-5- [p-(trifluoromethyl)phenyl]- 1,3-oxazol-4-yl } -2( 1H)-pyrimidinone, 248: 4-cyclopropyl-l-{2-(8-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl } -2 ( 1 H)-pyrimidinone, 249: 4-cyclopropyl- 1 - { 2-( 1 -isoquinolyl)-5- [p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 250: 4-cyclopropyl- 1 - { 2-(4-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 251: 4-cyclopropyl- 1 - { 2-(6-isoquinolyl)-5- [p-(trifluoromethyl)phenyl]- 1,3-oxazol-4-yl } -2( 1H)-pyrimidinone, 252: 1 - { 2-(6-cinnolinyl)-5- [p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -4-cyclopropyl-2(lH)-pyrimidinone, 253: 4-cyclopropyl- 1-{ 2-(l, 5-diaza-3-naphthyl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( lH)-pyrimidinone, 254: 4-cyclopropyl- 1 - { 2-( 1,6-diaza-3-naphthyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 255: 4-cyclopropyl- 1 - { 2-( 1 -methyl- lH-indazol-5 -yl)-5- [p-(trifluoromethyl)phenyl]- 1,3-oxazol-4-yl } -2(lH)-pyrimidinone, 256: 4-cyclopropyl- 1-{ 2-(l-methyl-lH- l,3-benzimidazol-5-yl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 257: 4-cyclopropyl- 1 - { 2- (2 -methyl-2H-indazol-5-yl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 258: 4-cyclopropyl-l-{2-(7-methyl-l,3a-diaza-2-indenyl)-5-[p-(trifluoromethyl)phenylJ-l,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 259: 4-cyclopropyl- 1 - { 2-( 1 -methyl- 1H- 1,6-diazainden-5-yl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, and 260: 4-cyclopropyl- 1-{ 2-( 1 -methyl- 1 H- 1,7-diazainden-5-yl)-5-[p-(trifluoromethyl)phenyl]- 1,3-oxazol-4-yl }-2( 1 H)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.Atty. Docket: UCSF-849WO

[0130] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 261: 4-cyclopropyl-l-{2-(l-methyl-lH-l,2,6-triazainden-5-yl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 262: 4-cyclopropyl- l-{2-(l-methyl-lH-l, 2, 3-benzotriazol-5-yl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( lH)-pyrimidinone, 263: 4-cyclopropyl- 1- { 2-(7 -methyl- 1,4,7a-triaza-3-indenyl)-5- [p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( 1H)-pyrimidinone, 264: 4-cyclopropyl-1-{2-(5-methyl-1,4,7a-triaza-3-indenyl)-5-[p-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}-2(1H)-pyrimidinone, 265: 4-cyclopropyl-l-{2-(6-methyl-l,4,7a-triaza-3-indenyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 266: 4-cyclopropyl- 1 - { 2-( 1 -methyl-6-isoquinolyl)-5- [p- (trifluoromethyl)phenyl] -l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 267: 4-cyclopropyl- l-{2-(2-methyl-6-quinolyl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 268: 4-cyclopropyl- 1 - { 2- (8 -methyl-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 269: 4-cyclopropyl- 1 -{ 2-(4-methyl-7-quinolyl)-5- [p-(trifluoromethyl)phenyll - 1,3-oxazol-4-yl } -2(lH)-pyrimidinone, 270: 4-cyclopropyl- l-{2-(3-methyl-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( lH)-pyrimidinone, 271: 4-cyclopropyl-1-{2-(1-methyl-7-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}-2(1H)-pyrimidinone, 272: 4-cyclopropyl- 1 - { 2-(8-methyl-3-quinolyl)-5- [p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2(lH)-pyrimidinone, 273: 4-cyclopropyl- l-{2-(6-methyl-2-quinolyl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 274: 4-cyclopropyl- 1 - { 2- (7 -methyl-3-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 275: 4-cyclopropyl-l-{2-(5-methyl-3-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 276: 4-cyclopropyl- 1 - { 2-(3-methy l-6-quinolyl)-5- [p- (trifluoromethyl)phenyl] -l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 277: 4-cyclopropyl- l-{2-(4-methyl-6-quinolyl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 278: 4-cyclopropyl- 1 - { 2-(8-methyl-6-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 279: 4-cyclopropyl-l-{2-(5-methyl-2-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, and 280: 4-cyclopropyl-1-{2-(1-fluoro-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}-2(1H)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.Atty. Docket: UCSF-849WO

[0131] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 281: 4-cyclopropyl-l-{2-(8-fluoro-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 282: 4-cyclopropyl- 1 -{ 2-(2-fluoro-6-quinolyl)-5-[p-(trifluoromethyl)phenyl]- 1,3-oxazol-4-yl } -2( 1H)-pyrimidinone, 283: 4-cyclopropyl-l-{2-(4-methyl-l,3-benzothiazol-2-yl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 284: 1-{2-(4-biphenylyl)-5-[p-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}-4-cyclopropyl-2(1H)-pyrimidinone, 285: 1 - { 2-(3-biphenylyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 286: 4-cyclopropyl-l-{2-(l-methoxy-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl } -2( lH)-pyrimidinone, 287: 4-cyclopropyl- 1 - { 2-(2-methyl- 1 -oxo-6-isoquinolyl)-5- [p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( lH)-pyrimidinone, 288: 4-cyclopropyl- 1 - { 2- (2 -methoxy-6-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 289: 4-cyclopropyl- 1 - { 2-(8-methoxy-3-quinolyl)-5- [p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2(lH)-pyrimidinone, 290: 4-cyclopropyl- l-{2-(3-cyclopropyl- 1,4, 7a-triaza-6-indenyl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 291: 4-cyclopropyl- 1 - { 2- [6 -methyl-4-(trifluoromethyl)-2-pyridyl]-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 292: 1-{2-(3-chloro-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}-4-cyclopropyl-2(1H)-pyrimidinone, 293: 4-cyclopropyl- 1 - { 2- [ l-(2-methoxyethyl)-6-isoquinolyl]-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 294: 4-cyclopropyl- 1 - { 2-[ 1 -(trifluoromethyl)-6-isoquinolyl] -5- [p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 295: 4-cyclopropyl- 1 - { 5- [p- (trifluoromethyl)phenyl] -2- [7-(trifluoromethyl)-3-quinolyl]- 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 296: 4-cyclopropyl- 1 - { 5-[p-(trifluoromethyl)phenyl] -2- [2-(trifluoromethyl)-6-quinolyl]- 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 297: 4-cyclopropyl-l-{2-(6-fluoro-3-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 298: 4-cyclopropyl- 1 - { 2-(4,5 -dimethyl-2-pyridyl)-5-[p-(trifhioromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 299: 4-cyclopropyl- 1-{ 2- (3-fluoro-6-methyl-2-pyridyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, and 300: 4-cyclopropyl-1-{2-(4-fluoro-6-methyl-2-pyridyl)-5-[p-(trifluoromethyl)phenyl]-1,3-oxazol-4-yl}-2(1H)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.Atty. Docket: UCSF-849WO

[0132] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 301: 4-cyclopropyl-l-{2-(6-fluoro-4-methyl-2-pyridyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 302: 4-cyclopropyl-l-{2-(6-methyl-3-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 303: 4-cyclopropyl- l-{2-(7-fluoro-3-quinolyl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 304: 4-cyclopropyl- 1 - { 2- (7 -methoxy-3-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 305: l-{2-(6-chloro-3-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 306: l-{2-(8-chloro-3-quinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 307: 4-cyclopropyl-l-{2-(6-methyl-l,3a-diaza-2-indenyl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( lH)-pyrimidinone, 308: 4-cyclopropyl- 1 - { 2-(2-isoindolinyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 309: 4-cyclopropyl- 1 - [5-(p-fluorophenyl)-2-( 1 -methyl-6-isoquinolyl)- 1,3-oxazol-4-yl] -2( 1H)-pyrimidinone, 310: 4-cyclopropyl-l-[5-(p-fluorophenyl)-2-phenyl-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 311: 4-cyclopropyl-l-[5-(p-fluorophenyl)-2-(m-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 312: 4-cyclopropyl-l-[5-(p-fluorophenyl)-2-(4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 313: 1-[2,5-bis(p-fluorophenyl)-1,3-oxazol-4-yl]-4-cyclopropyl-2(1H)-pyrimidinone, 314: 4-cyclopropyl-l-[2-(3-fluoro-6-methyl-2-pyridyl)-5-(p-fluorophenyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 315: 4-cyclopropyl-l-[2-(2,3-dihydro-l-benzofuran-6-yl)-5-(p-fluorophenyl)- 1,3-oxazol-4-yl]-2( lH)-pyrimidinone, 316: 4-cyclopropyl- l-[2-(2-cyclopropyl-4-pyrimidinyl)-5-(p-fluorophenyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 317: 4-cyclopropyl- 1-[5-(p-fluorophenyl)-2-(3-quinolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone. 318: 4-cyclopropyl- 1-[5-(p-fluorophenyl)-2-(2-methyl-6-quinolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 319: 4-cyclopropyl- 1 - [5-(p-fluorophenyl)-2-(6-fluoro-2-quinolyl)- 1,3-oxazol-4-yl] -2( lH)-pyrimidinone, and 320: l-[5-(4-chloro-3,5-difluorophenyl)-2-(4-methyl-2-pyridyl)-1.3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0133] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 321: l-[5-(4-chloro-3,5-difluorophenyl)-2-(5,6-dimethyl-2-pyridyl)-1.3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone.Atty. Docket: UCSF-849WO322: l-[5-(4-chloro-3,5-difluorophenyl)-2-(4,5-dimethyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 323: l-[2-(l,3a-diaza-2-indenyl)-5-(4-chloro-3,5-difluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 324: l-[5-(4-chloro-3,5-difluorophenyl)-2-( 1 -oxa-4-aza-6-indenyl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 325: l-[2-(l,3a,6-triaza-5-indenyl)-5-(4-chloro-3,5-difluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 326: l-[2-(l,5.7a-triaza-4-indenyl)-5-(4-chloro-3,5-difluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 327: l-[2-(4-aza-5-indanyl)-5-(4-chloro-3,5-difluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 328: l-[5-(4-chloro-3,5-difluorophenyl)-2-(4-methoxy-5-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 329: l-[5-(4-chloro-3,5-difluorophenyl)-2-(7-methyl-l,3a-diaza-2-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 330: l-[5-(4-chloro-3.5-difluorophenyl)-2-(l-methyl-lH-indazol-6-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 331: l-[5-(4-chloro-3, 5-difluorophenyl)-2-(l -methyl- lH-indazol-5-yl)- 1,3-oxazol-4-yll-4-cyclopropyl-2(lH)-pyrimidinone, 332: l-[5-(4-chloro-3,5-difluorophenyl)-2-(l-methyl- 1 H- 1,6-diazainden-5-yl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2 ( 1 H)-pyrimidinone, 333: 1 - [5-(4-chloro-3,5-difluorophenyl)-2-(l-methyl-lH-l,5-diazainden-6-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2( 1 H)-pyrimidinone, 334: 1 -[5-(4-chloro-3,5-difluorophenyl)-2-( 1 -methyl- 1 H-l,2,6-triazainden-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 335: l-[5-(4-chloro-3,5-difluorophenyl)-2-(l-methyl-lH-l,2,5-triazainden-6-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 336: l-[5-(4-chloro-3,5-difluorophenyl)-2-(l-methyl-lH-l,2,4-triazainden-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 337: l-[5-(4-chloro-3,5-difluorophenyl)-2-(7-methyl-l,3.3a-triaza-2-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 338: l-[5-(4-chloro-3,5-difluorophenyl)-2-(l-methyl-lH-l,2,5-triazainden-4-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 339: l-[5-(4-chloro-3,5-difluorophenyl)-2-(2-methyl-2H- 1,2,5-triazainden-4-yl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, and 340: l-[5-(4-chloro-3,5-difluorophenyl)-2-(l-methyl-lH-l,4,6-triazainden-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0134] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 341: l-[5-(4-chloro-3,5-Atty. Docket: UCSF-849WOdifluorophenyl)-2-(2-methyl-2H- 1,2,4-triazainden-5-yl)- 1,3-oxazol-4-yl]-4-cyclopropyl-2(l H)-pyrimidinone, 342: l-[5-(4-chloro-3,5-difluorophenyl)-2-(2-methyl-l,3a,6-triaza-5-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 343: l-[5-(4-chloro-3,5-difluorophenyl)-2-(l-methyl- 1 H- 1,3,5 -triazainden-6-yl)- 1,3 -oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 344: 1 -[5-(4-chloro-3,5-difluorophenyl)-2-(2-methyl-2H-l,2,6-triazainden-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 345: l-[5-(4-chloro-3.5-difluorophenyl)-2-(3-methyl-2,3a,6-triaza-7-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 346: l-[5-(4-chloro-3,5-difluorophenyl)-2-(l-methyl-lH-l,2,4,6-tetraazainden-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 347: l-[5-(4-chloro-3,5-difluorophenyl)-2-(l-methoxy-6-isoquinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 348: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 349: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(l-methyl-lH-l,2,6-triazainden-5-yl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 350: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(l-methyl-6-isoquinolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 351: 4-cyclopropyl-l-[5-(3.5-difluoro-4-tolyl)-2-(l-methoxy-6-isoquinolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 352: 4-cyclopropyl-l-[5-(3-fluoro-4-tolyl)-2-(l-methyl-lH-l,2,6-triazainden-5-yl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 353: 4-cyclopropyl-l-[5-(3-fluoro-4-tolyl)-2-(4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 354: 4-cyclopropyl-l-[5-(3-fluoro-4-tolyl)-2-(4-methyl-2-pyrimidinyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 355: 4-cyclopropyl-l-[2-(4,5-dimethyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 356: 4-cyclopropyl-l-[2-(4-cyclopropyl-2-pyrimidinyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 357: 4-cyclopropyl-l-[5-(3-fluoro-4-tolyl)-2-(4-methoxy-5-methyl-2-pyridyl)- 1,3-oxazol-4-yl] -2(1 H)-pyrimidinone, 358: 4-cyclopropyl- 1 - [5-(3-fluoro-4-tolyl)-2-(5-methoxy-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 359: l-[2-(4-chloro-5-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, and 360: 4-cyclopropyl-l-[5-(3-fluoro-4-tolyl)-2-(7-methyl-l,3a-diaza-2-indenyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0135] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 361: 4-cyclopropyl-l-{2-[4-(difluoromethyl)-2-pyridyl]-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 362: 4-Atty. Docket: UCSF-849WOcyclopropyl- l-[5-(3-fluoro-4-tolyl)-2-(6-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 363: 4-cyclopropyl-l-[5-(3-fluoro-4-tolyl)-2-(2-methyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 364: 4-cyclopropyl-l-[2-(5,6-dimethyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 365: 4-cyclopropyl-l-[5-(3-fluoro-4-tolyl)-2-(4-methoxy-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 366: 4-cyclopropyl-l-[5-(3-fluoro-4-tolyl)-2-(6-methoxy-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 367: 4-cyclopropyl-l-[2-(3-fluoro-6-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 368: 4-cyclopropyl-l-[2-(6-fluoro-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 369: 4-cyclopropyl-l-[2-(6-cyclopropyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 370: 4-cyclopropyl-l-[2-(4-cyclopropyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 371: 4-cyclopropyl-l-[2-(2-cyclopropyl-4-pyrimidinyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 372: 1-[2-(6-chloro-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 373: 4-cyclopropyl-l-[2-(4-difluoromethoxy-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 374: 4-cyclopropyl-l-{5-(3-fluoro-4-tolyl)-2-[4-(trifluoromethyl)-2-pyridyl]- 1,3-oxazol-4-yl}-2( lH)-pyrimidinone, 375: 4-cyclopropyl- 1 - [2-(4,6-dimethyl-2-pyrimidinyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 376: 4-cyclopropyl-l-{2-[6-(fluoromethyl)-5-methyl-2-pyridyl]-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 377: l-[5-(4-chloro-3-fluorophenyl)-2-(l-methyl-lH-l,2,4-triazainden-3-yl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 378: 1 - { 5-(4-chloro-3,5-difluorophenyl)-2-[ 1 -(2-methoxyethyl)- 1H- 1,2,6-triazainden-5-yl] - 1,3-oxazol-4-yl } -4-cyclopropyl-2(lH)-pyrimidinone, 379: l-[5-(4-chloro-3.5-difluorophenyl)-2-(2-methyl-4-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, and 380: l-[5-(4-chloro-3,5-difluorophenyl)-2-(2-methyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0136] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 381: l-[5-(4-chloro-3,5-difluorophenyl)-2-(2,6-dimethyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 382: 1 - [5- (4-chloro-3,5-difluorophenyl)-2- (3 -fluoro-6-methyl-2-pyridyl)- 1,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 383: l-[2-(l,3,3a-triaza-2-indenyl)-5-(4-Atty. Docket: UCSF-849WOchloro-3,5-difluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 384: l-[2-(3a,4,6-triaza-2-indenyl)-5-(4-chloro-3,5-difluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 385: l-[2-(l,4,7a-triaza-5-indenyl)-5-(4-chloro-3,5-difluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 386: l-[5-(4-chloro-3,5-difluorophenyl)-2-(6-methyl-l,3a-diaza-2-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 387: l-[5-(4-chloro-3.5-difluorophenyl)-2-(4-methyl-l,3.3a-triaza-2-indenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 388: 1 - { 5-(4-chloro-3,5-difluorophenyl)-2- [4-(trifluoromethyl)-2-pyridyl] -1,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 389: l-[5-(4-chloro-3,5-difluorophenyl)-2-(2-cyclopropyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 390: l-{ 5-(4-chloro-3,5-difluorophenyl)-2-(l,4-diazabicyclo[3.3.0]octa-2,4-dien-3-yl)-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 391: l-{5-(4-chloro-3,5-difluorophenyl)-2-(l,2-diazabicyclo[3.3.0]octa-2,4-dien-3-yl)-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 392: l-[5-(4-chloro-3,5-difluorophenyl)-2-(5,7-dihydro-4H-6-oxa-l,3a-diazainden-2-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 393: l-{5-(4-chloro-3,5-difluorophenyl)-2-[4-methoxy-5-(trifluoromethyl)-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, 394: l-[5-(4-chloro-3,5-difluorophenyl)-2-(6,7-dihydro-4H-5-oxa-l,7a-diazainden-2-yl)-l,3-oxazol-4-yl]- 4-cyclopropyl-2( lH)-pyrimidinone, 395: 4-cyclopropyl- 1 - { 2- [4- ( 1, 1 -difluoroethyl)-2-pyridyl] - 5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 396: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(5-fluoro-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 397: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(3-fluoro-6-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 398: 4-cyclopropyl-l-{5-(3,5-difluoro-4-tolyl)-2-[6-(fluoromethyl)-2-pyridyl]- 1.3-oxazol-4-yl}-2(lH)-pyrimidinone, 399: l-[2-(l,3a-diaza-2-indenyl)-5-(3,5-difluoro-4-tolyl)- 1.3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, and 400: 1 - [2-( 1,4,7a-triaza-3-indenyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0137] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 401: l-[2-(l,4,7a-triaza-5-indenyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 402: l-[2-(4-aza-5-indanyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 403: 4-cyclopropyl-l-[2-(4-cyclopropyl-2-pyrimidinyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-Atty. Docket: UCSF-849WOyl]-2(lH)-pyrimidinone, 404: 4-cyclopropyl- l-[2-(6-cyclopropyl-2-pyrazinyl)-5-(3,5-difluoro-4-tolyl)- 1,3-oxazol-4-yl]-2( lH)-pyrimidinone, 405: 4-cyclopropyl- 1 -[2-(6-cyclopropyl-4-pyrimidinyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 406: 4-cyclopropyl- 1-{5-(3,5-difluoro-4-tolyl)-2-[6-(fluoromethyl)-4-methyl-2-pyridyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 407: 4-cyclopropyl- 1 - { 5-(3,5-difluoro-4-tolyl)-2- [4-( 1 -fluoroethyl)-2-pyridyl] - 1.3-oxazol-4-yl } -2( 1 H)-pyrimidinone. 408: 4-cyclopropyl- 1 -[2-(2-cyclopropyl- 1,3-thiazol-4-yl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 409: 4-cyclopropyl- 1-[2-(2-cyclopropyl-l,3-thiazol-5-yl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 410: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(5-fluoro-4-methoxy-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 411: l-[2-(5-chloro-4-methyl-2-pyridyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl] -4-cyclopropyl-2( lH)-pyrimidinone, 412: 4-cyclopropyl- 1 - { 2-[4-(difluoromethyl)- 2-pyridyl]-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 413: l-[2-(4-chloro-5-fluoro-2-pyridyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 414: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(7-methyl-l,3a-diaza-2-indenyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 415: 4-cyclopropyl- l-[5-(3,5-difluoro-4-tolyl)-2-(2-methyl- l,3a-diaza- 5-indenyl)- 1,3-oxazol-4-yl] -2( lH)-pyrimidinone, 416: 1 - [2-(5-chloro-4-methoxy-2-pyridyl)-5 -(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 417: 4-cyclopropyl-l-[2-(l-cyclopropyl-4-pyrazolyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 418: 4-cyclopropyl- 1 - [2- (4-difluoromethoxy-2-pyridy l)-5-(3,5-difluoro-4-toly 1)- 1,3-oxazol-4-yl] -2( 1 H)-pyrimidinone, 419: 4-cyclopropyl- 1 - [5- (3,5 -diflu oro-4-tolyl)-2- (2-methyl-4-pyrimidinyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, and 420: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(5.6-dimethyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0138] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 421: 4-cyclopropyl- 1 -[5-(3,5-difluoro-4-tolyl)-2-(4,5-dimethyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 422: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(4-methoxy-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 423: 4-cyclopropyl- 1 -[5-(3,5-difluoro-4-tolyl)-2-(3-fluoro-4-methyl-2-pyridyl)- 1.3-oxazol-4-yl]-2(lH)-pyrimidinone, 424: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(5-methoxy-6-methyl-2-pyridyl)- 1,3-oxazol-4-yl] -2(1 H)-pyrimidinone, 425: 4-cyclopropyl- 1 - [5-Atty. Docket: UCSF-849WO(3,5-difluoro-4-tolyl)-2-(4-methoxy-5-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 426: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(6-methoxy-5-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 427: l-[2-(4-chloro-5-methyl-2-pyridyl)-5-(3.5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 428: 4-cyclopropyl- l-{2-[5-(difluoromethyl)-4-methyl-2-pyridyl] -5- (3,5-difluoro-4-tolyl)- 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 429: 4-cyclopropyl-l-{5-(3,5-difluoro-4-tolyl)-2-[4-(trifluoromethyl)-2-pyridyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 430: 4-cyclopropyl- l-[2-(5-cyclopropyl-4-methoxy-2-pyridyl)-5-(3, 5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone. 431: 4-cyclopropyl-l-[2-(2-cyclopropyl-4-pyrimidinyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 432: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(6-methoxy-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 433: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(6-fluoro-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 434: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(6-methoxy-4-methyl-2-pyridyl)- 1,3-oxazol-4-yl] -2(1 H)-pyrimidinone, 435: 4-cyclopropyl- 1 - [5 -(3,5-difluoro-4-tolyl)-2-(4-methoxy-6-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 436: l-[2-(6-chloro-4-methyl-2-pyridyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 437: l-[2-(4-chloro-6-methyl-2-pyridyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 438: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(l-methyl-lH-l,6-diazainden-5-yl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 439: 4-cyclopropyl-l-[5-(3,5-difluoro-4-tolyl)-2-(l-methyl-lH-l,2,5-triazainden-6-yl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, and 440: l-[2-(5-chloro-6-methoxy-2-pyridyl)-5-(3,5-difluoro-4-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0139] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 441: 4-cyclopropyl-l-{2-phenyl-5-[6-(trifluoromethyl)-3-pyridyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 442: 4-cyclopropyl- 1 - { 5 - [p- (difluoromethyl)phenyl] -2- ( 1 -methyl-6-isoquinolyl)- 1,3-oxazol-4-yl } -2(lH)-pyrimidinone, 443: 4-cyclopropyl- l-[2-(l-methyl-6-isoquinolyl)-5-(p-tolyl)- 1,3-oxazol-4-yl]-2(lH)-pyrimidinone, 444: 4-cyclopropyl- 1 -[5-(4-fluoro-5-methyl-2-pyridyl)-2-(1 -methyl-6-isoquinolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 445: l-[5-(p-chlorophenyl)-2-(l-methyl-6-isoquinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 446: 4-cyclopropyl- 1-{5-[ 1-Atty. Docket: UCSF-849WO(difluoromethyl)-3-pyrazolyl]-2-(l -methyl-6-isoquinolyl)- 1,3-oxazol-4-yl }-2(l H)-pyrimidinone, 447: l-[5-(l,7a-diaza-6-indenyl)-2-(l-methyl-6-isoquinolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(1 H)-pyrimidinone, 448: 4-cyclopropyl- 1 - { 5 - [3-fluoro-4- (fluoro methyl)phenyl] -2-( 1 -methyl-6-isoquinolyl)- 1,3-oxazol-4-yl }-2( lH)-pyrimidinone, 449: 4-cyclopropyl- l-[5-(4-cyclopropyl-3-fluorophenyl)-2-(l-methyl-6-isoquinolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 450: 4-cyclopropyl-l-{5-[4-(difluoromethyl)-3-fluorophenyl]-2-(l-methyl-6-isoquinolyl)-l,3-oxazol-4-yl } -2( lH)-pyrimidinone, 451: 4-cyclopropyl- 1 - { 2-( 1 -methyl-6-isoquinolyl)-5- [5 -(trifluoromethyl)-2-pyridyl]- 1,3-oxazol-4-yl } -2( lH)-pyrimidinone, 452: 4-cyclopropyl- 1 - { 2- ( 1 -methyl-6-isoquinolyl)-5-[6-(trifluoromethyl)-3-pyridyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 453: 4-cyclopropyl-l-[5-(3,5-difluorophenyl)-2-(l-methyl-6-isoquinolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 454: 4-cyclopropyl- l-[5-(3.4-difluorophenyl)-2-(4-methyl-2-pyridyl)- 1,3-oxazol-4-yl] -2( 1 H)-pyrimidinone, 455: 4-cyclopropyl- 1 -[2-(4-methyl-2-pyridyl)-5-(p-tolyl)- 1,3-oxazol-4-yl]-2(lH)-pyrimidinone, 456: l-[5-(p-chlorophenyl)-2-(4-methyl-2-pyridyl)-l,3-oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 457: 4-cyclopropyl- 1 - [5-(4-cyclopropyl-3-fluorophenyl)-2-(4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 458: l-[5-(p-chlorophenyl)-2-(4-fluoro-6-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 459: 1 - [5- (p-chlorophenyl)-2- (6-fluoro-4-methyl-2-pyridyl)- 1,3-oxazol-4-yl] -4-cyclopropyl-2(lH)-pyrimidinone, and 460: 4-cyclopropyl-l-[2-(4-fluoro-6-methyl-2-pyridyl)-5-(p-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0140] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 461: 4-cyclopropyl- 1- [2- (6-fluoro-4-methyl-2-pyridyl)-5-(p-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 462: 4-cyclopropyl-l-[5-(3-fluoro-4-methoxyphenyl)-2-(l-methyl-6-isoquinolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, 463: l-[2-(m-chlorophenyl)-5-(p-fluorophenyl)-l,3-oxazol-4-ylJ-4-isopropyl-2(lH)-pyrimidinone, 464: l-[2-(m-chlorophenyl)-5-(p-fluorophenyl)-l,3-oxazol-4-yl]-4-methyl-2( lH)-pyrimidinone, 465: 4-isobutyl- 1 - { 2-( 1 -methyl-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 466: (rac)-4-[(lS,2R)-2-fluorocyclopropyl] - 1 - { 2- ( 1 -methyl-6-isoquinolyl)-5- [p- (trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( lH)-pyrimidinone, 467: (rac)-4-[( 1 S,2S)-2-fluorocyclopropyl] - 1 - { 2-( 1 -methyl-6-Atty. Docket: UCSF-849WOisoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 468: 4-(2,2-difluorocyclopropyl)-l-{2-(l-methyl-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 469: 4-(3,3-difluorocyclobutyl)-l-{2-(l-methyl-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 470: l-[5-(p-chlorophenyl)-2-(m-tolyl)-l,3-oxazol-4-yl]-4-(3,3-difluorocyclobutyl)-2(lH)-pyrimidinone, 471: l-[5-(4-chloro- 3-fluorophenyl)-2-(6-methyl-2-pyridyl)-1.3-oxazol-4-yl]-4,5-dimethyl-2(lH)-pyrimidinone, 472: 4-cyclopropyl- 1 - { 5- [p-(trifluoromethyl)phenyl] -2- [2-(trifluoromethyl)-4-pyrimidinyl]- 1,3-oxazol-4-yl } -2 ( 1 H)-pyrimidinone, 473: 4-cyclopropyl- 1 - { 2-(4-methyl-2-pyridyl)-5- [p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } - 2( 1 H)-pyrimidinone, 474: 6- { 4-(4-cyclopropyl-2-oxo-l-pyrimidinyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-2-yl}-2-pyridinecarbonitrile, 475: 4-cyclopropyl-l-{2-(5,6-dimethyl-2-pyridyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 476: 4-cyclopropyl- 1-{2-(4, 6-dimethyl-2-pyridyl)-5-[p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -2( lH)-pyrimidinone, 477: 4-cyclopropyl- 1- { 2-(2-methoxy-4-pyrimidinyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 478: 1 - { 2- (m-chlorophenyl)-5- [p- (triflu oromethyl)phenyl] - 1,3-oxazol-4-yl } -4-cyclopropyl -2(lH)-pyrimidinone, 479: 4-cyclopropyl- l-{2-(6-cyclopropyl-2-pyridyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, and 480: 4-cyclopropyl- 1-{ 2-(2-methyl-2H-indazol-6-yl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0141] In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, the compound is selected from (Compound #: Compound Name,): 481: 4-cyclopropyl-l-{2-(8-fluoro-3-quinolyl)-5-[p-(trifluoromethyl)phenyll-l,3-oxazol-4-yl}-2(lH)-pyrimidinone. 482: 4-cyclopropyl-l-{2-(2,3-dihydro-l-benzofuran-6-yl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-5-methyl-2(lH)-pyrimidinone, 483: 4-cyclopropyl-5-methyl-l-{2-(m-tolyl)-5-[p-(trifluoromethyl)phenylj - 1,3-oxazol-4-yl } -2( 1 H)-pyrimidinone, 484: 4-cyclopropyl- 1 - { 2- (2 -methoxy-4-pyrimidinyl)-5- [p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -5-methyl-2( 1 H)-pyrimidinone, 485: 1 - { 2-(m-chlorophenyl)-5- [p-(trifluoromethyl)phenyl] - 1,3-oxazol-4-yl } -4-cyclopropyl-5-methyl-2(lH)-pyrimidinone, 486: 4-cyclopropyl-5-methyl-l-{2-(l-methyl-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, 487: l-{5-(4-chloro-3-fluorophenyl)-2-[2-(trifluoromethyl)-4-pyrimidinyl]-l,3-oxazol-4-yl}-4-cyclopropyl-5-Atty. Docket: UCSF-849WOmethyl-2(lH)-pyrimidinone, 488: l-[5-(4-chloro-3-fluorophenyl)-2-(6-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-5-methyl-2(lH)-pyrimidinone, 489: l-[5-(p-chlorophenyl)-2-(2-methyl-2H-indazol-5-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-5-fluoro-l,2-dihydro-2-pyrimidinone.490: l-[5-(p-chlorophenyl)-2-(6-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-5-fluoro-l,2-dihydro-2-pyrimidinone, 491: l-[2-(l,3a-diaza-2-indenyl)-5-(p-chlorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-5-fluoro-1.2-dihydro-2-pyrimidinone, 492: l-[2-(m-chlorophenyl)-5-(p-fluorophenyl)- 1,3 -oxazol-4-yl] -4-cyclopropyl-2( 1 H)-pyrimidinone, 493: 1 - [5-(p-chlorophenyl)-2-(m-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, 494: l-[2-(m-chlorophenyl)-5-(p-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-5-methyl-2(lH)-pyrimidinone, 495: l-[5-(4-chloro-3-fluorophenyl)-2-(m-tolyl)-l,3-oxazol-4-yl]-4-cyclopropyl-5-fluoro-l,2-dihydro-2-pyrimidinone, 496: l-[5-(4-chloro-3-fluorophenyl)-2-(m-chlorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-5-methoxy-l,2-dihydro-2-pyrimidinone, and 497: 5-chloro-l-[5-(4-chloro-3-fluorophenyl)-2-(m-chlorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-l,2-dihydro-2-pyrimidinone. In an exemplary embodiment, the compound, or a salt or a hydrate or a solvate thereof, is a radiolabeled version (18F, for example) of a compound described in this paragraph.

[0142] In an exemplary embodiment, the salt of a compound in this section is a pharmaceutically acceptable salt. In an exemplary embodiment, the salt of a compound described herein is a pharmaceutically acceptable salt. In an exemplary embodiment, the salt of a compound of the invention is a pharmaceutically acceptable salt.

[0143] In an exemplary embodiment, the second compound is disclosed herein, or a salt, hydrate or solvate thereof, where one or more of its atoms is replaced with [2H], [3H], [11C], [18F], or [13N]. In an exemplary embodiment, the second compound is a compound disclosed herein, or a salt, hydrate or solvate thereof, where one of its atoms is replaced with [2H], [3H], [11C], [18F], or [13N], In an exemplary embodiment, the second compound is a compound disclosed herein, or a salt, hydrate or solvate thereof, where one or more of its atoms is replaced with [2H], [3H], [11C], or [13N]. In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one or more of its Z moiety atoms is replaced with [2H], [3H], [11C], or [13N]. In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one of its Z moiety atoms is replaced with [2H], [3H], [11C], or [13N]. In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof,Atty. Docket: UCSF-849WOwherein one or more of its T moiety atoms is replaced with [2H], [3H], [11C], or [13N], In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one of its T moiety atoms is replaced with [2H], [3H], [11C], or [13N], In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one or more of its X moiety atoms is replaced with [2H], [3H], [11C], or [13N], In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one of its X moiety atoms is replaced with [2H], [3H], [11C], or [13N],

[0144] In an exemplary embodiment, the second compound is a compound disclosed herein, or a salt, hydrate or solvate thereof, where one or more of its atoms is replaced with [18F]. In an exemplary embodiment, the second compound is a compound disclosed herein, or a salt, hydrate or solvate thereof, where one of its atoms is replaced with [18F], In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, where one or more of its Z moiety atoms is replaced with [18F], In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one of its Z moiety atoms is replaced with [18F]. In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one or more of its T moiety atoms is replaced with [18F], In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one of its T moiety atoms is replaced with [18F], In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one or more of its X moiety atoms is replaced with [18F], In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one of its X moiety atoms is replaced with [18F]. In an exemplary embodiment, the labeled compounds described herein bind to 4-8 amino acid residues of amino acid residues 86-99 of SEQ ID NO: 9. In an exemplary embodiment, the second compound, or a salt or a hydrate or a solvate thereof, is l-[5-(4-chloro-3-fluorophenyl)-2-(6-(fluoro-18F)-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the second compound, or a salt or a hydrate or a solvate thereof, is 1 -{5-(4-chloro-3-fluorophenyl)-2-[6-((fluoro-18F)methyl)-4-methyl-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone. In an exemplary embodiment, the second compound, or a saltAtty. Docket: UCSF-849WOor a hydrate or a solvate thereof, is 4-cyclopropyl-l-[2-(6-(fluoro-18F)-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone. In an exemplary embodiment, the second compound, or a salt or a hydrate or a solvate thereof, is 4-cyclopropyl-l-{2-[6-((fluoro-18F)methyl)-5-methyl-2-pyridyl]-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl}-2(lH)-pyrimidinone. In an exemplary embodiment, the second compound, or a salt or a hydrate or a solvate thereof, is 1-(5-(4-chloro-3-fluorophenyl)-2-(7-((fluoro-18F)methyl)-5-methylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one. In an exemplary embodiment, the second compound, or a salt or a hydrate or a solvate thereof, is l-(5-(4-chloro-3-fluorophenyl)-2-(5-((fluoro-18F)methyl)-7-methylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one.

[0145] In an exemplary embodiment, the second compound is a compound disclosed herein, or a salt, hydrate or solvate thereof, wherein one or more of its atoms is replaced with [2H], [3H], [11C], [13N], [15O], [18F], [52Mn], [55Co], [64Cu], [67Ga], [68Ga], [82Rb], [89Zr], [99mTc], [111In], [123I], or [201Tl], In an exemplary embodiment, the second compound is a compound disclosed herein, or a salt, hydrate or solvate thereof, wherein one or more of its atoms is replaced with [15O], [52Mn], [55Co], [64Cu], [67Ga], [68Ga], [82Rb], [89Zr], [99mTc], [111In], [123I], or [201Tl], In an exemplary embodiment, the second compound is a compound disclosed herein, or a salt, hydrate or solvate thereof, wherein one of its atoms is replaced with [15O], [52Mn], [55Co], [64Cu], [67Ga], [68Ga], [82Rb], [89Zr], [99mTc], [111In], [123I], or [201Tl], In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, where one or more of its Z moiety atoms is replaced with [15O], [52Mn], [55Co], [64Cu], [67Ga], [68Ga], [82Rb], [89Zr], [99mTc], [111In], [123I], or [201Tl]. In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one of its Z moiety atoms is replaced with [15O], [52Mn], [55Co], [64Cu], [67Ga], [68Ga], [82Rb], [89Zr], [99mTc], [111In], [123I], or [201Tl], In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one or more of its T moiety atoms is replaced with [15O], [52Mn], [55Co], [64Cu], [67Ga], [68Ga], [82Rb], [89Zr], [99mTc], [111In], [123I], or [201Tl], In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one of its T moiety atoms is replaced with [15O], [52Mn], [55Co], [64Cu], [67Ga], [68Ga], [82Rb], [89Zr], [99mTc], [111In], [123I], or [201Tl]. In an exemplary embodiment, the secondAtty. Docket: UCSF-849WOcompound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one or more of its X moiety atoms is replaced with [15O], [52Mn], [55Co], [64Cu], [67Ga], [68Ga], [82Rb], [89Zr], [99mTc], [111In], [123I], or [201Tl]. In an exemplary embodiment, the second compound is according to a formula described herein, or a salt, hydrate or solvate thereof, wherein one of its X moiety atoms is replaced with [15O], [52Mn], [55Co], [64Cu], [67Ga], [68Ga], [82Rb], [89Zr], [99mTc], [111In], [123I], or [201Tl]. In an exemplary embodiment, the radiolabeled compound disclosed herein can be used as an imaging agent for positron emission tomography (PET), single photon emission computed tomography (SPECT), or autoradiography. In an exemplary embodiment, the invention provides a radiolabeled compound, which is a compound disclosed herein where one or more of its atoms is replaced with [11C], [13N], [15O], [18F], [52Mn], [55Co], [64Cu], [68Ga], [82Rb], or [89Zr], In an exemplary embodiment, the invention provides a radiolabeled compound, which is a compound disclosed herein where one or more of its atoms is replaced with [67Ga], [99mTc], [111In], [123I], or [201Tl]. In an exemplary embodiment, the invention provides a radiolabeled compound, which is a compound disclosed herein where one or more of its atoms is replaced with [11C], [13N], [15O], [18F], [52Mn], [55Co], [64Cu], [68Ga], [82Rb], or [89Zr],IIIb. First Compound

[0146] In an exemplary embodiment, the first compound is not detectable (or essentially not detectable) by the technique. In an exemplary embodiment, the first compound is not detectable (or essentially not detectable) by PET. In an exemplary embodiment, when the technique is positron emission tomography (PET), then the first compound does not comprise a radiolabeled atom. In an exemplary embodiment, when the technique is positron emission tomography (PET), then the first compound does not compriseUC,13N,15O,18F,52Mn,55Co,64Cu,68Ga,82Rb, or89Zr.

[0147] In an exemplary embodiment, the first compound is part of a complex which is not detectable (or essentially not detectable) by the technique. In an exemplary embodiment, the first compound is part of a complex which is not detectable (or essentially not detectable) by PET. In an exemplary embodiment, when the technique is positron emission tomography (PET), then the first compound is part of a complex that does not comprise a radiolabeled atom. In an exemplary embodiment, when the technique is positron emission tomography (PET), then theAtty. Docket: UCSF-849WOfirst compound is part of a complex that does not compriseUC,13N,15O,18F,52Mn,55Co,64Cu,68Ga,82Rb, or89Zr.

[0148] In an exemplary embodiment, the first compound is not detectable (or essentially not detectable) by SPECT. In an exemplary embodiment, when the technique is SPECT, then the first compound does not comprise a radiolabeled atom. In an exemplary embodiment, when the technique is SPECT, then the first compound does not comprise67Ga,99mTc,111In,123I, or201Tl.

[0149] In an exemplary embodiment, the first compound is part of a complex which is not detectable (or essentially not detectable) by SPECT. In an exemplary embodiment, when the technique is SPECT, then the first compound is part of a complex which does not comprise a radiolabeled atom. In an exemplary embodiment, when the technique is SPECT, then the first compound is part of a complex which does not comprise67Ga,99mTc,111In,123I, or201Tl.

[0150] In an exemplary embodiment, the first compound is not detectable (or essentially not detectable) by autoradiography. In an exemplary embodiment, when the technique is autoradiography, then the first compound does not comprise a radiolabeled atom. In an exemplary embodiment, when the technique is autoradiography, then the first compound does not comprise3H,11C,13N.15O,18F.52Mn,55Co,64Cu,68Ga,82Rb, or89Zr.

[0151] In an exemplary embodiment, the first compound is part of a complex which is not detectable (or essentially not detectable) by autoradiography. In an exemplary embodiment, when the technique is autoradiography, then the first compound is part of a complex that does not comprise a radiolabeled atom. In an exemplary embodiment, when the technique is autoradiography, then the first compound is part of a complex that does not comprise3H,11C,13N,15O,18F,52Mn,55Co,64CU,68Ga,82Rb, or89Zr.

[0152] In an exemplary embodiment, the first compound has a structure presented in section IIIa1, wherein the radiolabeled atom is replaced with a non-radiolabeled atom. In an exemplary embodiment, the first compound has a structure of an imaging compound described in a reference mentioned in section IIIa1, wherein the radiolabeled atom in the imaging compound is replaced with a non-radiolabeled atom.Atty. Docket: UCSF-849WOIIIc. Administering

[0153] In an exemplary embodiment, the first compound is administered to the patient prior to, coincident with, and / or after of the administration of the second compound to the patient. In an exemplary embodiment, the first compound is administered to the patient prior to, coincident with, and / or within about 24 hours after the administration of the second compound to the patient. In an exemplary embodiment, the first compound is administered prior to the administration of the second compound. In an exemplary embodiment, the first compound is administered from 5 days to 30 seconds prior to the administration of the second compound. In an exemplary embodiment, the first compound is administered coincident with the administration of the second compound. In an exemplary embodiment, the first compound is administered at the same time (within one second) as the administration of the second compound. In an exemplary embodiment, the first compound is administered from 30 seconds to 1 second prior to the administration of the second compound. In an exemplary embodiment, the first compound is administered within about 24 hours of the administration of the second compound. In an exemplary embodiment, the first compound is administered within about 5 minutes of the administration of the second compound. In an exemplary embodiment, the first compound is administered from 1 second after to about 5 minutes after the administration of the second compound. In an exemplary embodiment, the first compound is administered from about 5 minutes to about 24 hours after the administration of the second compound.

[0154] In an exemplary embodiment, the ratio of first compound to second compound administered to the patient is from 3:1 to 30,000:1. In an exemplary embodiment, the ratio of first compound to second compound administered to the patient is from 3:1 to 10:1, from 3:1 to 100:1, from 3:1 to 1,000:1, from 3:1 to 10,000:1, from 10,000:1 to 30,000:1, from 1,000:1 to 30,000:1, from 100:1 to 30,000:1, or from 10:1 to 30,000:1.IIId. Allowing

[0155] In an exemplary embodiment, the time allowed after administration for the first compound to bind the protein aggregates is from about 5 seconds to about 24 hours, from about 30 minutes to about 150 minutes, from about 30 minutes to about 120 minutes, from about 45 minutes to about 120 minutes, from about 45 minutes to about 75 minutes, or from about 60 minutes to about 12 hours.Atty. Docket: UCSF-849WO

[0156] In an exemplary embodiment, the time allowed after administration for the second compound to bind the protein aggregates is from about 5 seconds to about 24 hours, from about 30 minutes to about 150 minutes, from about 30 minutes to about 120 minutes, from about 45 minutes to about 120 minutes, from about 45 minutes to about 75 minutes, or from about 60 minutes to about 12 hours.

[0157] The time allowed for the first compound and for the second compound to bind the protein aggregates may overlap.IIIe. Detecting the binding of the second compound

[0158] In an exemplary embodiment, the second compound was detected via PET. The following is an example of general PET conditions for detecting a second compound in a mouse. For mice experiments. nanoScan microPET / CT (Mediso, Budapest, Hungary) is used. [18F]-Compound (~7.4 MBq / mouse) is administered intravenously by tail vein injection or retro orbitally via syringe injection (RO) while mice are under anesthesia. Following18F-compound injection, whole body dynamic scans (0-120 min PET acquisition followed by CT scan for anatomic reference) are acquired with warming and constant monitoring. Analysis is performed using VivoQuant software (Invicro, Boston MA).

[0159] The following is an example of general PET conditions for detecting a second compound in a human. Each patient receives a bolus intravenous injection of18F-compound (dose range: 188.7-355.2 MBq) prior to a total of 94 min of PET-MR scanning performed as three sequential temporal scanning sessions concluding at 190 min after tracer injection. Regional tissue volumes of interest were defined for multiple organs and time-integrated activity coefficients (TIACs) were derived. The TIACs were used to calculate estimates of absorbed and effective doses using OLINDA software.

[0160] In an exemplary embodiment, the second compound was detected via autoradiography. The following is an example of autoradiographic conditions. Serial dilutions of3H-Compound A were prepared in DPBS at the following concentrations: 4pM, 2pM, 1.5pM, IpM, 500nM, and 250nM. A low-binding 96-well flat-bottom plate (Greiner Bio-One Cat no 07000090) for each concentration was then prepared by adding 50pl (IxlO5cells) of the cell-derived aggregates described herein were added in replicates of 6 for each time point. At the appropriate time before harvest, 50p 1 of the relevant dilution of3H-Compound A was added to each of the 6 replicateAtty. Docket: UCSF-849WOwells. Between timepoints, plates were incubated at room temperature and shaken at 650RPM using an orbital shaker. Plates were then sealed (Thermo Cat no 1424518) between timepoints. At the indicated timepoints, glass fiber filters (GF / B (Revvity Cat no 1450-521) pre-treated with 0.3% polyethylenamine (PEI, Sigma Cat No 408727) were loaded onto a Microbeta Filtermat-96 Cell harvester (Revvity). Filters were wetted by running 300ml of DPBS through the harvester system. Samples from the 96-well plate were then harvested onto their respective filters, and all wells were rinsed 4 times with approximately 200pl DPBS followed by rinsing 4 times with approximately 200 l 70% ethanol. After rinsing, the filters were promptly transferred face-down to sheets of siliconized release paper. The filters were dried on a hot plate set to 120°C for a minimum of 10 minutes. Once dry, a sheet of MeltiLex-B solid scintillator (Revvity, Cat no 1450-442) was placed on the back of the filter and allowed to melt and adhere for no less than 3 minutes, and until uniform and sufficient coverage was observed. The filters were removed from the hotplate and left to cool to room temperature. The filters were then sealed into sample bags and data was collected using the MicroBeta2(Revvity).IIIf. Protein Aggregates

[0161] In an exemplary embodiment, the protein aggregates are in the brain, central nervous system, eye, heart, and / or kidney of the patient. In an exemplary embodiment, the protein aggregates are in the brain of the patient.

[0162] In an exemplary embodiment, the protein aggregates are amyloid aggregates. In an exemplary embodiment, the protein aggregates are tau aggregates, alpha-synuclein aggregates, amyloid-0 aggregates, mutants of amyloid-0 peptide aggregates, neuroserpin aggregates, actin aggregates, ferritin aggregates, superoxide dismutase aggregates, Huntington aggregates, Huntington aggregates with polyQ expansion, PrP aggregates, PrP fragment aggregates, ataxin aggregates, ataxin with polyQ expansion aggregates, TATA box-binding protein aggregates, TATA box-binding protein with polyQ expansion aggregates, androgen receptor aggregates, androgen receptor with polyQ expansion aggregates, atrophin 1 aggregates, atrophin 1 with polyQ expansion aggregates, Abri aggregates, Adan aggregates, immunoglobulin light chain aggregates, immunoglobulin light chain fragment aggregates, immunoglobulin heavy chain aggregates, immunoglobulin heavy chain fragment aggregates, fragment of serum amyloid A protein aggregates, wild-type transthyretin aggregates, mutant of transthyretin aggregates. 02-Atty. Docket: UCSF-849WOmicroglobulin aggregates, N-terminal fragment of ApoAI aggregates, N-terminal fragment of ApoAII aggregates, N-terminal fragment of ApoAIV aggregates, ApoCII aggregates, ApoCIII aggregates, fragment of gelsolin mutant aggregates, mutant of lysozyme aggregates, variant of fibrinogen a-chain aggregates, mutant of cy statin C aggregates, ZAP (islet amyloid polypeptide) aggregates, lactadherin C2-like domain aggregates, leukocyte cell-derived chemotaxin 2 aggregates, gelactin 7 aggregates, comeodesmosin aggregates, odontogenic ameloblast-associated protein aggregates, semenogelin 1 aggregates, calcitonin aggregates, atrial natriuretic factor aggregates, prolactin aggregates, insulin aggregates, enfuvirtide aggregates, medin aggregates, C-terminal fragment of kerato-epithelin aggregates, lactoferrin aggregates, y-Crystallin aggregates, lung surfactant protein C aggregates, TAF15 aggregates, TAF16 aggregates. FUS (fused in sarcoma) aggregates, TMEM (transmembrane) aggregates, or keratin aggregates. In an exemplary embodiment, the protein aggregates are tau aggregates, alpha-synuclein aggregates, amyloid-beta aggregates, or a combination thereof. In an exemplary embodiment, the protein aggregates are alpha- synuclein aggregates. In an exemplary embodiment, the protein aggregates are alpha- synuclein aggregates associated with multiple system atrophy (MSA). In an exemplary embodiment, the protein aggregates are alpha-synuclein aggregates associated with multiple system atrophy strain A (MSA- A). In an exemplary embodiment, the protein aggregates are alpha- synuclein aggregates associated with multiple system atrophy strain B (MSA-B). In an exemplary embodiment, the protein aggregates are alpha-synuclein aggregates associated with multiple system atrophy strain A (MSA-A) and multiple system atrophy strain B (MSA-B).IIIg. Diagnosing and / or Monitoring Treatment

[0163] In another aspect, the invention provides a method for diagnosing and / or monitoring the treatment of a disease and / or condition described herein in a patient. In an exemplary embodiment, the method comprises: a) administering a first compound and a second compound to the patient, wherein the first compound is not detectable (or essentially not detectable) by the technique, and wherein the second compound is detectable by the technique; b) allowing the first compound and the second compound to bind the protein aggregates; and c) detecting the binding of the second compound to the protein aggregates, thereby measuring the protein aggregates in the patient. In an exemplary embodiment, the method comprises: a) administering a first compound not detectable (or essentially not detectable) by the technique to the patient; b)Atty. Docket: UCSF-849WOallowing the first compound to bind the protein aggregates; c) administering a second compound detectable by the technique to the patient; d) allowing the second compound to bind the protein aggregates; and e) detecting the binding of the second compound to the protein aggregates, thereby measuring the protein aggregates in the patient. In an exemplary embodiment, the method comprises: a) administering a second compound detectable by the technique to the patient; b) allowing the second compound to bind the protein aggregates; c) administering a first compound detectable by the technique to the patient; d) allowing the first compound to bind the protein aggregates; and e) detecting the binding of the second compound to the protein aggregates, thereby measuring the protein aggregates in the patient.

[0164] In an exemplary embodiment, the disease and / or condition is associated with protein aggregates described herein. In an exemplary embodiment, the disease and / or condition is a tauopathy, an alpha-synucleinopathy, or an amyloidopathy. In an exemplary embodiment, the disease and / or condition is a neurodegenerative disease, non-neuropathic systemic amyloidosis, and / or non-neuropathic localized disease. In an exemplary embodiment, the disease and / or condition is a neurodegenerative disease, which is selected from the group consisting of Alzheimer disease, familial encephalopathy with neuroserpin inclusion bodies, neuroferritinopathy, spongiform encephalopathies, Parkinson disease, dementia with Lewy bodies, frontotemporal dementia with Parkinsonism, amyotrophic lateral sclerosis, Huntington disease, spinocerebellar ataxias (e.g. Spinocerebellar ataxia 17), spinal and bulbar muscular atrophy, hereditary dentatorubral-pallidoluysian atrophy, familial British dementia, and familial Danish dementia. In an exemplary embodiment, the disease and / or condition is a non-neuropathic systemic amyloidosis, which is selected from the group consisting of AL amyloidosis, AH amyloidosis, AA amyloidosis, familial Mediterranean fever, senile systemic amyloidosis, familial amyloidotic polyneuropathy, haemodialysis-related amyloidosis, ApoAI amyloidosis, ApoAII amyloidosis, ApoAIV amyloidosis, ApoCII amyloidosis, ApoCIII amyloidosis, Finnish hereditary amyloidosis, lysozyme amyloidosis, fibrinogen amyloidosis, and Icelandic hereditary cerebral amyloid angiopathy. In an exemplary embodiment, the disease and / or condition is a non-neuropathic localized disease, which is selected from the group consisting of Type II diabetes, aortic media amyloidosis, LECT2 amyloidosis, localized cutaneous amyloidosis, hypotrichosis simplex of the scalp, calcifying epithelial odontogenic tumor, senile seminal vesicle amyloidosis, medullary carcinoma of the thyroid, atrialAtty. Docket: UCSF-849WOamyloidosis, hereditary cerebral hemorrhage with amyloidosis, pituitary prolactinoma, injection-localized amyloidosis, aortic medial amyloidosis, hereditary lattice corneal dystrophy, comeal amyloidosis associated with trichiasis, cataract, pulmonary alveolar proteinosis, inclusion-body myositis, and cutaneous lichen amyloidosis. In an exemplary embodiment, the disease and / or condition is includes, without limitation, transmissible spongiform encephalopathies (such as Creutzfeldt-Jakob disease (CJD)), multiple system atrophy (MSA), Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis (ALS), Amyotrophic lateral sclerosis / Parkinsonism-dementia complex, anti-IgLON5-related tauopathy, Caribbean Parkinsonism, Chronic traumatic encephalopathy, Dementia with Lewy Bodies (DLB), Diffuse neurofibrillary tangles with calcification, Down syndrome, Familial British dementia, Familial Danish dementia, Niemann-Pick disease-type C, Non-Guamanian motor neuron disease with neurofibrillary tangles, Postencephalitic Parkinsonism, Primary age-related tauopathy, Progressive ataxia and palatal tremor, Tangle-only dementia, Familial frontotemporal dementia and Parkinsonism, Pick's disease. Argyrophilic grain disease, Corticobasal degeneration, Guadeloupean Parkinsonism, Globular glial tauopathy, Huntington's disease, Progressive supranuclear palsy, SLC9a-related Parkinsonism, or Tau astrogliopathy. In some embodiments, the disease and / or condition is multiple system atrophy (MSA). In some embodiments, the disease and / or condition is multiple system atrophy A strain (MSA-A). In some embodiments, the disease and / or condition is multiple system atrophy B strain (MSA-B). In some embodiments, the disease and / or condition is Parkinson’s disease. In some embodiments, the disease and / or condition is Dementia with Lewy Bodies (DLB). In some embodiments, the disease and / or condition is Alzheimer’s disease. In some embodiments, the disease and / or condition is multiple system atrophy (MSA) associated with alpha- synuclein aggregates. In some embodiments, the disease and / or condition is multiple system atrophy strain-A (MSA-A) associated with alpha-synuclein aggregates. In some embodiments, the disease and / or condition is multiple system atrophy strain-B (MSA-B) associated with alpha-synuclein aggregates. In some embodiments, the disease and / or condition is multiple system atrophy strain-A (MSA-A) and multiple system atrophy strain-B (MSA-B) associated with alpha-synuclein aggregates.

[0165] In another aspect, the invention provides a method of measuring the clinical efficacy of a therapeutic agent for a disease associated with protein aggregates in a patient, comprising: a) before treatment with said therapeutic agent, administering a first compound to the patient,Atty. Docket: UCSF-849WOherein the first compound binds to the protein aggregates and is not detectable (or essentially not detectable) by the technique, and administering a second compound to the patient, wherein the second compound binds to the protein aggregates and is detectable by the technique, wherein the first compound is administered prior to, and / or coincident with, the second compound; b) measuring the amount of protein aggregates in the patient's brain tissue before treatment; c) after treatment with said therapeutic agent, administering a first compound to the patient, wherein the first compound binds to the protein aggregates and is not detectable (or essentially not detectable) by the technique, and administering a second compound to the patient, wherein the second compound binds to the protein aggregates and is detectable by the technique, wherein the first compound is administered prior to, and / or coincident with, the second compound; d) measuring the amount of protein aggregates in the patient's brain tissue after treatment; and e) analyzing whether said therapeutic agent maintained or reduced the amount of protein aggregates in the patient, thereby measuring the clinical efficacy of the therapeutic agent.IIIh. Patient

[0166] Examples of possible patients include, but are not limited to, humans (i.e., a male or female human of any age group, e.g., a pediatric subject (e.g, infant, child, adolescent) or adult subject (e.g., young adult, middle-aged adult, or senior adult)) and / or other non-human animals, for example, mammals (e.g., primates (e.g., cynomolgus monkeys, rhesus monkeys)); commercially relevant mammals such as cats and / or dogs. In certain embodiments, the animal is a mammal. The animal may be a male or female and at any stage of development. A non-human animal may be a transgenic animal. In another exemplary embodiment, the subject is a human.IV. Diagnostic Combinations

[0167] In another aspect, the invention provides a diagnostic combination, comprising: a) a nonradiolabeled first compound, or a salt, hydrate, or solvate thereof; b) a radiolabeled second compound, or a salt, hydrate, or solvate thereof, wherein the radiolabeled compound and the nonradiolabeled compound bind to the protein aggregates. In an exemplary embodiment, the diagnostic combination is useful for diagnosing a disease and / or condition described herein. In an exemplary embodiment, the diagnostic combination is useful for diagnosing multiple system atrophy (MSA). In an exemplary embodiment, the diagnostic combination is useful for diagnosing multiple system atrophy strain A (MSA-A). In an exemplary embodiment, theAtty. Docket: UCSF-849WOdiagnostic combination is useful for diagnosing multiple system atrophy strain B (MSA-B). In an exemplary embodiment, the diagnostic combination is useful for diagnosing multiple system atrophy strain A (MSA-A) and multiple system atrophy strain B (MSA-B). In an exemplary embodiment, the first compound, or a salt, hydrate, or solvate thereof in the diagnostic combination is described herein. In an exemplary embodiment, the second compound, or a salt, hydrate, or solvate thereof in the diagnostic combination is described herein. In an exemplary embodiment, in the diagnostic combination, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is 1-(5-(4-chloro-3-fluorophenyl)-2-(5,7-dimethylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic combination, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl- 1 - [5-(p-fluorophenyl)-2-( 1 -methyl-6-isoquinolyl)- 1,3-oxazol-4-yl] -2( 1H)-pyrimidinone, or a salt, hydrate, or solvate thereof. In an exemplary embodiment, in the diagnostic combination, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl-l-{2-(l-methyl-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone or a salt, hydrate, or solvate thereof. In an exemplary embodiment, in the diagnostic combination, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl-l-{2-[6-(fluoromethyl)-5-methyl-2-pyridyl]-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, or a salt, hydrate, or solvate thereof. In an exemplar}' embodiment, in the diagnostic combination, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is l-(5-(4-chloro-3-fluorophenyl)-2-(6-(fluoromethyl)-4-methylpyridin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt, hydrate, or solvate thereof. In an exemplary embodiment, in the diagnostic combination, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl-l-[2-(6-fluoro-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, or a salt, hydrate, or solvate thereof. In an exemplary embodiment, in the diagnostic combination, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is 1-Atty. Docket: UCSF-849WO[5-(4-chloro-3-fluorophenyl)-2-(6-fluoro-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, or a salt, hydrate, or solvate thereof.

[0168] In an exemplary embodiment, in the diagnostic combination, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is l-[5-(4-chloro-3-fluorophenyl)-2-(6-(fluoro-18F)-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic combination, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is l-{5-(4-chloro-3-fluorophenyl)-2-[6-((fluoro-18F)methyl)-4-methyl-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic combination, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl-l-[2-(6-(fluoro-18F)-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic combination, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl-l-{2-[6-((fluoro-18F)methyl)-5-methyl-2-pyridyl]-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic combination, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is l-(5-(4-chloro-3-fluorophenyl)-2-(7-((fluoro-18F)methyl)-5-methylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic combination, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is l-(5-(4-chloro-3-fluorophenyl)-2-(5-((fluoro-18F)methyl)-7-methylpyrazolo[l,5-aJpyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt or a hydrate or a solvate thereof.

[0169] In an exemplary embodiment, in the diagnostic combination, the first compound, or salt, hydrate, or solvate thereof is l-(5-(4-chloro-3-fluorophenyl)-2-(5,7-dimethylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt or a hydrate or a solvate thereof, and the second compound, or a salt, hydrate, or solvate thereof, is l-[5-(4-chloro-Atty. Docket: UCSF-849WO3-fluorophenyl)-2-(6-(fluoro-18F)-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof.V. Diagnostic Compositions

[0170] In another aspect, the invention provides a diagnostic composition, comprising: a) a nonradiolabeled first compound, or a salt, hydrate, or solvate thereof; b) a radiolabeled second compound, or a salt, hydrate, or solvate thereof; and c) a pharmaceutically acceptable excipient, wherein the radiolabeled compound and the non-radiolabeled compound bind to the protein aggregates. In an exemplary embodiment, the diagnostic composition is useful for diagnosing multiple system atrophy (MSA). In an exemplary embodiment, the diagnostic composition is useful for diagnosing multiple system atrophy strain A (MSA- A). In an exemplary embodiment, the diagnostic composition is useful for diagnosing multiple system atrophy strain B (MSA-B). In an exemplary embodiment, the diagnostic composition is useful for diagnosing multiple system atrophy strain A (MSA-A) and multiple system atrophy strain B (MSA-B). In an exemplary embodiment, the first compound, or a salt, hydrate, or solvate thereof in the diagnostic composition is described herein. In an exemplary embodiment, the second compound, or a salt, hydrate, or solvate thereof in the diagnostic composition is described herein. In an exemplary embodiment, in the diagnostic composition, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is l-(5-(4-chloro-3-fluorophenyl)-2-(5,7-dimethylpyrazolo[l,5-aJpyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic composition, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl-l-[5-(p-fluorophenyl)-2-(l-methyl-6-isoquinolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, or a salt, hydrate, or solvate thereof. In an exemplary embodiment, in the diagnostic composition, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl-l-{2-(l-methyl-6-isoquinolyl)-5-[p-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone or a salt, hydrate, or solvate thereof. In an exemplary embodiment, in the diagnostic composition, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl-l-{2-[6-(fluoromethyl)-5-methyl-2-pyridyl]-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, or a salt, hydrate,Atty. Docket: UCSF-849WOor solvate thereof. In an exemplary embodiment, in the diagnostic composition, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is l-(5-(4-chloro-3-fluorophenyl)-2-(6-(fluoromethyl)-4-methylpyridin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt, hydrate, or solvate thereof. In an exemplary embodiment, in the diagnostic composition, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl-l-[2-(6-fluoro-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, or a salt, hydrate, or solvate thereof. In an exemplary embodiment, in the diagnostic composition, the second compound, or salt, hydrate, or solvate thereof is as described herein, and the first compound, or a salt, hydrate, or solvate thereof, is 1-[5-(4-chloro-3-fluorophenyl)-2-(6-fluoro-4-methyl-2-pyridyl)-1,3-oxazol-4-yl]-4-cyclopropyl-2(1H)-pyrimidinone, or a salt, hydrate, or solvate thereof.

[0171] In an exemplary embodiment, in the diagnostic composition, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is l-[5-(4-chloro-3-fluorophenyl)-2-(6-(fluoro-18F)-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic composition, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is l-{5-(4-chloro-3-fluorophenyl)-2-[6-((fluoro-18F)methyl)-4-methyl-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic composition, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl-l-[2-(6-(fluoro-18F)-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic composition, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is 4-cyclopropyl-l-{2-[6-((fluoro-18F)methyl)-5-methyl-2-pyridyl]-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl}-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic composition, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is l-(5-(4-chloro-3-fluorophenyl)-2-(7-((fluoro-18F)methyl)-5-methylpyrazolo[l,5-a]pyrimidin-2-Atty. Docket: UCSF-849WOyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one, or a salt or a hydrate or a solvate thereof. In an exemplary embodiment, in the diagnostic composition, the first compound, or salt, hydrate, or solvate thereof is as described herein, and the second compound, or a salt, hydrate, or solvate thereof, is l-(5-(4-chloro-3-fluorophenyl)-2-(5-((fluoro-18F)methyl)-7-methylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt or a hydrate or a solvate thereof.

[0172] In an exemplary embodiment, in the diagnostic composition, the first compound, or salt, hydrate, or solvate thereof is l-(5-(4-chloro-3-fluorophenyl)-2-(5,7-dimethylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one, or a salt or a hydrate or a solvate thereof, and the second compound, or a salt, hydrate, or solvate thereof, is l-[5-(4-chloro-3-fluorophenyl)-2-(6-(fluoro-18F)-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone, or a salt or a hydrate or a solvate thereof.EXAMPLES

[0173] The following examples are put forth to provide those of ordinary skill in the art with a complete disclosure and description of how to make and use the present invention and are not intended to limit the scope of what the inventors regard as their invention nor are they intended to represent that the experiments below are all or the only experiments performed. Efforts have been made to ensure accuracy with respect to numbers used (e.g. amounts, temperature, etc.) but some experimental errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, molecular weight is weight average molecular weight, temperature is in degrees Centigrade, and pressure is at or near atmospheric.Atty. Docket: UCSF-849WOEXAMPLE 1Second Compound Syntheses involving ¹⁸F: ¹⁸F-368. 4-cyclopropyl-1-[2-(6-(fluoro-¹⁸F)-4-methyl-2-pyridyl]-5-(3-fluoro-4-tolyl)-1,3-oxazol-4-yl]-2(1H)-pyrimidinone:2-([l,l '-biphenyl ]-2-ylthio )-6-bromo-4-methylpyridine

[0174] To a flame-dried tube with a screw cap (15 mL) under argon, Pd2(dba)s (23.5 mg, 25.6 umol. 5 mol%), DPEphos (27.6 mg, 51.2 umol, 10 mol%). 2,6-dibromo-4-methylpyridine (129 mg, 0.512 mmol, 1 equiv.), S-([l,l’-biphenyl]-2-yl) ethanethioate (129 mg, 0.563 mmol, 1.1 equiv.) and dry toluene (4 mL) were added sequentially. The resulting mixture was degassed by bubbling argon through the mixture for 5 minutes. Then, potassium tert-butoxide (1 M in THF, 0.615 mL, 0.615 mmol, 1.2 equiv.) was added and the tube was sealed. The reaction mixture was then heated at 110 °C and stirred for 16 hours. After cooling to room temperature, the reaction mixture was concentrated in vacuo. The crude product was purified by flash column chromatography (silica gel, 0-20% EtOAc in heptane) to afford 2-([l,l'-biphenyl]-2-ylthio)-6-bromo-4-methylpyridine (104 mg, 0.290 mmol, 57%). This material was used directly in the next step.l-(2-( 6-( [1,1 '-biphenyl ]-2-ylthio)-4-methylpyridin-2-yl)-5-( 3-fluoro-4-methylphenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one

[0175] In a resealable vial, a suspension of 2-([l,l'-biphenyl]-2-ylthio)-6-bromo-4-methylpyridine (34.6 mg, 1.2 Eq, 97.1 pmol), 4-cyclopropyl-1-(5-(3-fluoro-4-methylphenyl)oxazol-4-yl)pyrimidin-2(1H)-one (25.2 mg, 1 Eq, 80.9 pmol), cesium carbonateAtty. Docket: UCSF-849WO(55.4 mg, 2.1 Eq, 170 pmol), bromo(1,10-phenanthroline)(triphenylphosphine)copper(I) (2.37 mg, 0.05 Eq, 4.05 pmol), and Pd(PPh₃)₄ (4.68 mg, 0.05 Eq, 4.05 pmol) in dioxane (0.7 mL) was purged with nitrogen for 5 minute. The mixture was then sealed and stirred at 105 °C for 6 hours. Upon cooling, the reaction mixture was diluted with EtOAc and concentrated onto silica gel. This material was purified by silica gel column chromatography (4 g Isco Cartridge, 0-100% EtOAc in heptane). The product containing fractions were concentrated to dryness and triturated with EtOAc in heptane to provide 1-(2-(6-([1,1'-biphenyl]-2-ylthio)-4-methylpyridin-2-yl)-5-(3-fluoro-4-methylphenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (18.8 mg, 32.0 µmol, 39.6%) as a white solid.

[0176] LC-MS: [M+H]+= 587.25-(6-(4-(4-cyclopropyl-2-oxopyrimidin-l(2H)-yl)-5-(3-fluoro-4-methylphenyl)oxazol-2-yl)-4-methylpyridin-2-yl )-5H-dibenzo[b, d ] thiophen- 5 -ium trifluoromethanesulfonate

[0177] To a stirring solution of 1-(2-(6-([1,1'-biphenyl]-2-ylthio)-4-methylpyridin-2-yl)-5-(3-fluoro-4-methylphenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (18.8 mg, 1 Eq, 32.0 µmol) in anhydrous acetonitrile (0.3 mL) were added glacial acetic acid (7.70 mg, 7.34 pL, 4 Eq, 128 pmol) and periodic acid (14.6 mg, 2 Eq, 64.1 pmol). The resulting reaction mixture was heated to 60 °C for 2 hours. At this time, the reaction was cooled to -40 °C and trifluoroacetic acid (3.65 mg, 2.47 pL, 1 Eq, 32.0 pmol) was added. Then, a solution of trifluoromethanesulfonic anhydride (10.8 mg, 6.46 pL, 1.2 Eq, 38.5 pmol) in dichloromethane (0.5 mL) was added, and the resulting solution was stirred for 5 minutes. The reaction was brought to room temperature, quenched with saturated aqueous sodium bicarbonate, and diluted with dichloromethane. The layers were separated, and the aqueous layer was extracted twice with dichloromethane. The combined organic layers were dried over MgSO₄, filtered, and concentrated in vacuo. The crude product was purified by normal phase flash column chromatography (4 g, 0-20% MeOH in DCM) to afford 5-(6-(4-(4-cyclopropyl-2-oxopyrimidin-1(2H)-yl)-5-(3-fluoro-4-methylphenyl)oxazol-2-yl)-4-methylpyridin-2-yl)-5H-dibenzo[b,d]thiophen-5-ium trifluoromethanesulfonate (10.2 mg, 13.9 µmol, 43.3 %).

[0178] LCMS: [M]+ m / z = 585.2

[0179] NMR (400 MHz, CDCl₃) δ8.47 (d, J = 8.1 Hz, 2H), 8.36 (s, 1H), 8.16 (d, J = 7.8 Hz, 2H), 7.99 (s, 1H), 7.90 (t, J = 7.6 Hz, 2H), 7.72 (t, J = 7.8 Hz, 2H), 7.49 (d, J = 6.8 Hz, 1H), 7.22Atty. Docket: UCSF-849WO(d, J = 8.1 Hz, 1H), 7.01 (t, J= 10.7 Hz, 2H), 6.40 (d, 7= 6.9 Hz, 1H), 2.56 (s, 3H), 2.33 (s, 3H), 1.99 - 1.90 (m, 1H), 1.41 (dd, J= 7.5, 3.9 Hz, 2H), 1.22 - 1.12 (m, 2H).4-cyclopropyl-1-[2-(6-(fluoro-¹⁸F)-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-1,3-oxazol-4-yl]-2(1H)-pyrimidinone [Compound ¹⁸F-368]

[0180] A solution of K18F in HI18O (1 mL, 220 mCi) was loaded onto a QMA cartridge (waters, WAT023525) that had been prepped by washing with 5 mL of 1 M sodium carbonate followed by 10 mL of type 1 water. Once loaded, the K18F was eluted from the cartridge with 1 mL of eluting solution (50% MeCN in type 1 water, 1 mg / mL potassium carbonate, 6.2 mg / mL Kryptofix [2.2.2.]). The K18F solution was then concentrated under vacuum with a positive pressure of nitrogen. Dry MeCN was added to the dried material and the solution was concentrated under vacuum with a positive pressure of nitrogen. This process was repeated 4 times. Once dry, the K18F residue measured 203 mCi of activity. To the residue was added 5-(6-(4-(4-cyclopropyl-2-oxopyrimidin-1(2H)-yl)-5-(3-fluoro-4-methylphenyl)oxazol-2-yl)-4-methylpyridin-2-yl)-5H-dibenzo[b,d]thiophen-5-ium trifluoromethanesulfonate (2.3 mg, solution in 250 µL of DMSO) and the reaction was sealed and heated at 90 °C for 10 minutes. After 10 minutes, the activity of the solution was 192 mCi. The crude reaction was mixed with an additional 250 uL of DMSO and directly injected onto a semi-prep HPLC column (Luna 5u Cl 8(2)). The mixture was eluted at 4 mL / min using 10% MeCN in water for 10 minutes.During this time, unreacted K18F eluted with 21.4 mCi of activity. At 10 minutes, the elution solution was changed to 90% MeCN in water. The product eluted at 19 minutes with 56.3 mCi of activity in 3 mL of solvent. This solution was mixed with 25 mL of type 1 water and loaded onto a C18 cartridge (5 mL / min using a syringe pump, waters, WAT023501) that had been prepped by rinsing with 5 mL of EtOH followed by 10 mL of type 1 water. Once loaded, the product was eluted from the C 18 cartridge using 0.5 mL of absolute EtOH to give 4-cyclopropyl-1-[2-(6-(fluoro-¹⁸F)-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-1,3-oxazol-4-yl]-2(1H)-pyrimidinone (solution in 0.5 mL of EtOH, 41.9 mCi, 19% radiochemical yield (uncorrected)). The identity and purity of the product was confirmed by coinjection of 1 uL of the product solution with 5 uL of a 10 mM solution of 4-cyclopropyl-1-(5-(3-fluoro-4-methylphenyl)-2-(6-fluoro-4-methylpyridin-2-yl)oxazol-4-yl)pyrimidin-2(1H)-one onto an analytical HPLC (100 mm Luna 5u Cl 8(2) column). The product eluted at 9 minutes with overlap of the RAD and UV signals. Single injection of 1 uL of the product solution gave >99% radiochemical purity of 4-Atty. Docket: UCSF-849WOcyclopropyl- l-[2-(6-(fluoro-18F)-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]- 2(1 H)-pyrimidinone.Synthesis of18F-24. l-f5-(4-chloro-3-fluorophenyl)-2-(6-(fluoro-18F}-4-methyl-2-pyridyl}-l,3-oxazol-4-yll-4-cyclopropyl-2(lH)-pyrimidinone:

[0181] l-[5-(4-chloro-3-fluorophenyl)-2-(6-(fluoro-18F)-4-methyl-2-pyridyl)-l,3-oxazol-4-yl]-4-cyclopropyl-2(lH)-pyrimidinone was synthesized in an analogous fashion to 4-cyclopropyl-l-[2- (6-(fluoro-18F)-4-methyl-2-pyridyl)-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone from the appropriate starting materials.Additional Synthesis of ¹⁸F-24. 1-[5-(4-chloro-3-fluorophenyl)-2-(6-(fluoro-¹⁸F)-4-methyl-2-pyridyl)-1,3-oxazol-4-yl]-4-cyclopropyl-2(1H)-pyrimidinone:C₂Cl₆, LiHMDS, THF 1. XPhos Pd G3, B₂(Pin)₂, KOAc 2. Pd(dppf), Cs₂CO₃DMSO, 10 minutes, 180 °C Kryptofix

[0222] , K2CO3, K18F1 -( 2-chloro-5-( 4- chloro- 3 -fluorophenyl )oxazol-4-yl )-4-cyclopropylpyrimidin-2( IHfone

[0182] To a -78 °C suspension of 1-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (750 mg, 1 Eq, 2.26 mmol) in THF (18 mL) was added lithium bis(trimethylsilyl)amide (2.71 mL, 1 molar in THF, 1.2 Eq, 2.71 mmol) dropwise over 2 minutes. The reaction mixture was stirred at -78 °C one hour. The flask was transferred to a -40 °C bath, and the mixture was stirred for an additional 15 minutes. The reaction was returned to -78 °C and allowed to cool for 10 minutes. Then, perchloroethane (642 mg, 1.2 Eq, 2.71 mmol) was dissolved in 1 mL THF and added dropwise. The reaction mixture was then stirred for 15 minutes at temperature. The reaction was then transferred again to a -40 °C bath and stirred for 30 minutes. The reaction was quenched with saturated aqueous ammonium chloride and stirred while warming to room temperature. The mixture was extracted with DCM (3 times). The organics were combined, dried over anhydrous magnesium sulfate, and concentrated. TheAtty. Docket: UCSF-849WOcrude product was purified by normal phase chromatography (40 g silica gel, 40-100% EtOAc in heptane) affording 1-(2-chloro-5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (575 mg, 1.57 mmol, 69.5%) as a solid.

[0183] LCMS: (M+H)+= 366.0.

[0184] ’H NMR (400 MHz, DMSO) 58.06 (d, 7 = 7.0 Hz, 1H), 7.75 (t, J= 8.1 Hz, 1H), 7.49 (dd, J = 10.2, 2.0 Hz, 1H), 7.20 (d,.7= 8.4 Hz, 1H), 6.68 (d, 7 = 7.0 Hz, 1H), 1.15 (d, 7= 6.7 Hz, 4H).1-(5-(4-chloro-3-fluorophenyl)-2-(4-methyl-6-nitropyridin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one

[0185] To a suspension of 2-bromo-4-methyl-6-nitropyridine (60 mg, 1.0 Eq, 0.276 mmol), potassium acetate (54 mg, 2 Eq, 0.553 mmol), and bis(pinacolato)diboron (140 mg, 2 Eq, 0.553 mmol), in dioxane (5 mL) was added XPhos PdG3 (23.4 mg, 0.1 Eq, 0.0276 mmol) and the mixture was sealed and stirred at 100 °C for 3 hours. After cooling to room temperature, to this mixture were added 1-(2-chloro-5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (75.9 mg, 0.75 Eq, 0.207 mmol), cesium carbonate (180 mg, 2 Eq, 0.553 mmol), and Pd(dppf) (22.6 mg, 0.1 Eq, 0.0276 mmol) and the mixture was sealed and stirred at 100 °C for 1.5 hours. The mixture was diluted with EtOAc, filtered, and the organic solution concentrated under reduced pressure. The resulting residue was purified by normal phase column chromatography (0-10% MeOH in DCM) to provide 1-(5-(4-chloro-3-fluorophenyl)-2-(4-methyl-6-nitropyridin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (2.1 mg, 0.0040 mmol, 2%) as an off-white solid.

[0186] LCMS: (M+H)+= 468.0.

[0187] A solution of K18F in H218O (1 mL, 294 mCi) was loaded onto a QMA cartridge (waters, WAT023525) that had been prepped by washing with 5 mL of 1 M sodium carbonate followed by 10 mL of type 1 water. Once loaded, the K18F was eluted from the cartridge with 1 mL of eluting solution (50% MeCN in type 1 water, 1 mg / mL potassium carbonate. 6.2 mg / mL Kryptofix [2.2.2.]). The K18F solution was then concentrated under vacuum with a positive pressure of nitrogen. Dry MeCN was added to the dried material and the solution was concentrated under vacuum with a positive pressure of nitrogen. This process was repeated 4 times. Once dry, the K18F residue measured 257 mCi of activity. To the residue was added l-(5-Atty. Docket: UCSF-849WO(4-chloro-3-fluorophenyl)-2-(4-methyl-6-nitropyridin-2-yl)oxazoL4-yl)-4-cyclopropylpyrimidin-2( 1 H)-one (2.1 mg, solution in 250 uL of DMSO) and the reaction was sealed and heated at 180 °C for 10 minutes. After 10 minutes, the activity of the solution was 242 mCi. The crude reaction was mixed with an additional 250 uL of DMSO and directly injected onto a semi-prep HPLC column (Luna 5u C 18(2)). The mixture was eluted at 4 mL / min using 10% MeCN in water for 10 minutes. During this time, unreacted K18F eluted. At 10 minutes, the elution solution was changed to 90% MeCN in water. The product eluted at 21 minutes with 4.3 mCi of activity in 2 mL of solvent. This solution was mixed with 25 mL of type 1 water and loaded onto a C18 cartridge (5 mL / min using a syringe pump, waters, WAT023501) that had been prepped by rinsing with 5 mL of EtOH followed by 10 mL of type 1 water. Once loaded, the product was eluted from the C 18 cartridge using 0.5 mL of absolute EtOH to give 4-cyclopropyL l-[2-(6-(fhioro-18F)-4-methyl-2-pyridyl)-5-(3-fluoro-4-chlorophenyl)- 1,3-oxazol-4-yl]-2( 1 H)-pyrimidinone (solution in 0.5 mL of EtOH, 2.0 mCi, 1% radiochemical yield (uncorrected)). The identity and purity of the product was confirmed by coinjection of 1 pL of the product solution with 5 pL of a 10 mM solution of 4-cyclopropyl-l-(5-(3-fluoro-4-chlorophenyl)-2-(6-fhioro-4-methylpyridin-2-yl)oxazol-4-yl)pyrimidin-2( lH)-one onto an analytical HPLC (100 mm Luna 5u Cl 8(2) column). The product eluted at 9 minutes with overlap of the RAD and UV signals. Single injection of 1 pL of the product solution gave >99% radiochemical purity of 4-cyclopropyl-l-[2-(6-(fluoro-18F)-4-methyl-2-pyridyl)-5-(3-fluoro-4-chlorophenyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone.Atty. Docket: UCSF-849WOSynthesis ofl8F-l 13. l-(5-(4-chloro-3-fhiorovhenyl)-2-f6-( ( fluoro-18F }methylj-4-methyl-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lFF)-vyrimidinone:NaBH4, TBSCI, MeOH, Imidazole rt, 16 h DCM, rt, 2 h

[0188] To a solution of methyl 6-chloro-4-methylpicolinate (200 mg, 1 Eq, 1.08 mmol) in MeOH (5 mL) was added sodium borohydride (81.5 mg, 2 Eq, 2.16 mmol). The resulting clear colorless reaction mixture was stirred at room temperature for 16 hours. The methanol was removed under vacuum, and the residual semi-solid was mixed with ethyl acetate, washed with water and brine, dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure to provide (6-chloro-4-methylpyridin-2-yl)methanol (170 mg, 1.08 mmol, 100%) as a syrup.

[0189] ’H NMR (400 MHz. CHLOROFORM-d) 5 ppm 7.06 (brd. J = 8.55 Hz, 2H), 4.70 (s, 2H), 2.36 (s, 3H).2-(((tert-butyldimethylsilyl)oxy)methyl)-6-chloro-4-methylpyridine

[0190] In a 50 mL single-necked round bottom flask were combined (6-chloro-4-methylpyridin- 2-yl)methanol (850 mg, 1 Eq, 5.39 mmol), DCM (20 mL), TBS-C1 (1.06 g. 1.3 Eq, 7.01 mmol), and imidazole (734 mg, 2 Eq, 10.8 mmol). The resulting suspension was stirred at room temperature for 2 hours. The reaction mixture was diluted with DCM, washed with water and brine, dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure to provide crude compound. This material was purified by normal phase flash chromatography (12Atty. Docket: UCSF-849WOg silica gel, 10% EtOAc in hexanes) to provide 2-(((fert-butyldimethylsilyl)oxy)methyl)-6- chloro-4-methylpyridine (1.3 g, 4.8 mmol, 89 %) as a syrup.

[0191] NMR (400 MHz. CHLOROFORM-d) 5 ppm 7.24 (s, 1H), 7.00 - 7.02 (m, 1H), 4.76 (s. 2H). 2.36 (s, 3H). 0.95 (s, 9H), 0.12 (s, 6H).l-(2-(6-(((tert-butyldimethylsilyl)oxy)methyl)-4-methylpyridm-2-yl)-5-(4-chloro-3-fluorophenyl )oxazol-4-yl )-4-cyclo- propylpyrimidin-2( IHfone

[0192] In a 25 mL sealable tube were combined l-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4- cyclopropylpyrimidin-2(l / 7)-one (50.0 mg, 1 Eq, 151 pmol), 2-(((tert- butyldimethylsilyl)oxy)methyl)-6-chloro-4-methylpyridine (82.0 mg, 2 Eq, 301 pmol), and toluene (4 mL), and the mixture was purged with argon for 10 minutes. Then, potassium carbonate (62.5 mg, 3 Eq, 452 pmol), pivalic acid (6.16 mg, 6.80 pL, 0.4 Eq, 60.3 pmol), bis(l- adamantyl)-butyl-phosphane (5.40 mg, 0.1 Eq, 15.1 pmol), and mesylate[(di(l-adamantyl)-n- butyl- phosphine)-2-(2'-amino-l,l'-biphenyl)Jpalladium(Il) (11.0 mg, 0.1 Eq, 15.07 pmol) were added, and the mixture was purged with argon for 10 minutes. Finally, the tube was sealed and heated to 110 °C for 16 hours. Upon cooling to room temperature, the reaction mixture was diluted with DCM and filtered. The filtrate was concentrated under reduced pressure to yield crude compound. This material was purified by normal phase flash chromatography (4 g silica gel, 0-100% EtOAc in hexanes) to provide l-(2-(6-(((t -butyldimethylsilyl)oxy)methyl)-4- methylpyridin-2-yl)-5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclo- propylpyrimidin-2( 1 H)- one (50 mg, 88 pmol, 58%) as a solid.

[0193] (+esi) [M+H]+= 567.6.

[0194] NMR (400 MHz. DMSO-tfc) 5 ppm 8.17 (d, J= 6.97 Hz, 1H), 8.02 (s. 1H), 7.78 (t, J = 8.16 Hz, 1H), 7.57 (dd, J= 10.13, 1.97 Hz, 1H), 7.45 (s, 1H), 7.25 - 7.36 (m, 1H), 6.71 (d, J = 6.97 Hz, 1H), 4.84 (s, 2H), 2.47 (s, 3H), 2.08 - 2.19 (m, 1H), 1.16 - 1.22 (m, 4H), 0.95 (s, 9H), 0.15 (s, 6H).1 -( 5-( 4-chloro-3-fluorophenyl)-2-( 6-( hydroxymethyl )-4-methylpyridin-2-yl foxazol-4-yl )-4- cyclopropylpyrimidin-2( IHfone

[0195] In a 50 mL single-necked round bottom flask were combined l-(2-(6-(((t - butyldimethylsilyl)oxy)methyl)-4-methylpyridin-2-yl)-5-(4-chloro-3-fluorophenyl)oxazol-4-yl)- 4-cyclopropylpyrimidin-2(lH)-one (180 mg, 1 Eq, 317 pmol), MeOH (3 mL), and PTSOH (90.6Atty. Docket: UCSF-849WOmg, 1.5 Eq, 476 pmol). The mixture was stirred at room temperature for 30 minutes. Aqueous sodium bicarbonate was added to the reaction mixture, and the resulting solid was collected by vacuum filtration. This material was then washed with water and dissolved in 10% methanol in DCM. The solution was dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure. The crude compound was then purified by normal phase flash chromatography (12 g silica gel, 5% methanol in DCM) to yield 90 mg of a solid. This material was purified again by preparative TLC (200 pm plate, 5% methanol in DCM) to afford l-(5-(4-chloro-3-fluorophenyl)-2-(6-(hydroxymethyl)-4-methylpyridin-2-yl)-oxazol-4-yl)-4-cyclopropylpyrimidin-2(l / 7)-one (43 mg, 91 pmol, 29%) as a solid.

[0196] (+esi) [M+H]+= 452.5.

[0197] ’H NMR (400 MHz, DMSO-d6) 5 ppm 8.18 (d, J= 6.97 Hz, 1H), 8.01 (s, 1H), 7.78 (s, 1H), 7.60 (dd, J = 10.19, 1.91 Hz, 1H). 7.53 (s, 1H), 7.32 (dd, J= 8.42, 1.45 Hz, 1H), 6.71 (d, J = 6.84 Hz, 1H), 5.57 (t, J = 5.85 Hz, 1H), 4.65 (d, J = 5.79 Hz, 2H). 2.47 (s, 3H), 2.10 - 2.17 (m, 1H), 1.15 - 1.22 (m, 4H).(6-(5-( 4-chloro-3 -fluorophenyl)-4-( 4-cyclopropyl-2-oxopyrimidin-l ( 2H)-yl )oxazol-2-yl)-4-methylpyridin-2 -yl [methyl methane sulfonate

[0198] To a solution of l-(5-(4-chloro-3-fluorophenyl)-2-(6-(hydroxymethyl)-4-methylpyridin-2-yl)-oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one (41.6 mg, 92.3 pmol, 1.0 Eq) in dichloromethane (2 mL) were added triethylamine (32.2 pL, 231 pmol. 2.5 Eq) and methanesulfonic anhydride (41.4 mg, 231 pmol, 2.5 Eq). The mixture was stirred at 22 °C for 2 hours. The reaction mixture was quenched by the addition of water. The mixture was then extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with brine (15 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure to give (6-(5-(4-chloro-3-fluorophenyl)-4-(4-cyclopropyl-2-oxopyrimidin-l(2H)-yl)oxazol-2-yl)-4-methylpyridin-2-yl)methyl methanesulfonate (39.5 mg, 74.4 pmol, 81%) as a solid.

[0199] (+esi) [M+H]+= 531.1.l-f5-(4-chloro-3-fluorophenyl}-2-[6-((fluoro-18F)methyl)-4-methyl-2-pyridyl]-l,3-oxazol-4-yU-4-cyclvpropyl-2(IH)-pyrimidinone [Compound1SF-113]

[0200] A solution of K18F in H218O (1 mL, 245 mCi) was loaded onto a QMA cartridge (waters, WAT023525) that had been prepped by washing with 5 mL of 1 M sodium carbonate followedAtty. Docket: UCSF-849WOby 10 mL of type 1 water. Once loaded, the K18F was eluted from the cartridge with 1 mL of eluting solution (50% MeCN in type 1 water, 1 mg / mL potassium carbonate, 6.2 mg / mL Kryptofix [2.2.2.]). The K18F solution was then concentrated under vacuum with a positive pressure of nitrogen. Dry MeCN was added to the dried material and the solution was concentrated under vacuum with a positive pressure of nitrogen. This process was repeated 4 times. Once dry, the K18F residue measured 221 mCi of activity. To the residue was added 5(6-(5-(4-chloro-3-fluorophenyl)-4-(4-cyclopropyl-2-oxopyrimidin-l (2H)-yl)oxazol-2-yl)-4-methylpyridin-2-yl)methyl methanesulfonate (5.0 mg, solution in 250 pL of DMSO) and the reaction was sealed and heated at 180 °C for 10 minutes. After 10 minutes, the activity of the solution was 210 mCi. The crude reaction was mixed with an additional 250 pL of DMSO and directly injected onto a semi-prep HPLC column (Luna 5u Cl 8(2)). The mixture was eluted at 4 mL / min using 10% MeCN in water for 10 minutes. During this time, unreacted K18F eluted with 87.7 mCi of activity. At 10 minutes, the elution solution was changed to 90% MeCN in water. The product eluted at 22 minutes with 14 mCi of activity in 2 mL of solvent. This solution was mixed with 25 mL of type 1 water and loaded onto a C18 cartridge (5 mL / min using a syringe pump, waters, WAT023501) that had been prepped by rinsing with 5 mL of EtOH followed by 10 mL of type 1 water. Once loaded, the product was eluted from the C18 cartridge using 0.50 mL of absolute EtOH. The first 150 pL of EtOH was discarded and the second 350 pL of EtOH was collected to give l-{5-(4-chloro-3-fluorophenyl)-2-[6-((fluoro-18F)methyl)-4-methyl-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyl-2(lH)-pyrimidinone (solution in 0.35 mL of EtOH, 10.4 mCi, 4.7% radiochemical yield (uncorrected)). The identity and purity of the product was confirmed by co-injection of 1 pL of the product solution with 5 pL of a 10 mM solution of l-(5-(4-chloro-3-fluorophenyl)-2-(6-(fluoromethyl)-4-methylpyridin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lF / )-one onto an analytical HPLC (100 mm Luna 5u C18(2) column, 60% MeCN in water with 0.1% formic acid). The product eluted at 8.4 minutes with overlap of the RAD and UV signals. Single injection of 1 pL of the product solution (100 mm Luna 5u C 18(2) column, 60% MeCN in water with 0.1% formic acid) gave >99% radiochemical purity of l-{5-(4-chloro-3-fluorophenyl)-2-[6-((fluoro-18F)methyl)-4-methyl-2-pyridyl]-l,3-oxazol-4-yl}-4-cyclopropyL2 ( 1 H) -py rimidinone.Atty. Docket: UCSF-849WOSynthesis ofl8F- 516

[0201] l-(5-(4-chloro-3-fluorophenyl)-2-(7-((fluoro-18F)methyl)-5-methylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2( l / 7)-one can be synthesized in an analogous fashion to l-{5-(4-chloro-3-fluorophenyl)-2-[6-((fluoro-18F)methyl)-4-methyl-2-pyridyl]- 1,3-oxazol-4-yl }-4-cyclopropyl-2( lH)-pyrimidinone from the appropriate starting material (2-(5-(4-chloro-3-fluorophenyl)-4-(4-cyclopropyl-2-oxopyrimidin-l(2H)-yl)oxazol-2-yl)-5-methylpyrazolo [ 1,5 -a] pyrimidin-7-yl)methyl methanesulfonate.Synthesis of18F- 517

[0202] l-(5-(4-chloro-3-fhiorophenyl)-2-(5-((fluoro-18F)methyl)-7-methylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2( lH)-one can be synthesized in an analogue fashion to l-{5-(4-chloro-3-fluorophenyl)-2-[6-((fluoro-18F)methyl)-4-methyl-2-pyridyl]- 1,3-oxazol-4-yl }-4-cyclopropyl-2( lH)-pyrimidinone from the appropriate starting material (2-(5-(4-chloro-3-fluorophenyl)-4-(4-cyclopropyl-2-oxopyrimidin-l(2H)-yl)oxazol-2-yl)-7-methylpyrazolo [ 1, 5 -a] pyrimidin-5 -yl)methyl methanesulfonate.Synthesis of Compound18F-376. 4-cyclopropyl-l-{2-[6-((fluoro-18F)methyl)-5-methyl-2-pyridyl]-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yll-2(lH)-pyrimidinone:4-cycl()pr()pyl-l-(5-(3-flu()r()-4-meihylphenyl)-2-(6-(h\'dr()X\'melh\'r)-5-inelh\'lpyridin-2-yl)oxazol-4-yl)pyrimidin-2(lH)-one

[0203] In a resealable vial, a suspension of (6-chloro-3-methylpyridin-2-yl)methanol (190 mg, 1.5 Eq, 1.20 mmol), 4-cyclopropyl-l-(5-(3-fluoro-4-methylphenyl)oxazol-4-yl)pyrimidin-2(l / / )- one (0.250 g, 1 Eq, 803 pmol), cesium carbonate (549 mg, 2.1 Eq, 1.69 mmol), bromo(l,10-Atty. Docket: UCSF-849WOphenanthroline)(triphenylphosphine)copper(I) (23.5 mg, 0.05 Eq, 40.2 pmol), and tetrakis(triphenylphosphine)palladium(0) (46.4 mg, 0.05 Eq, 40.2 pmol) was purged with nitrogen for 5 minute. The vial was then sealed and stirred at 105 °C for 6 hours. Upon cooling to room temperature, the reaction mixture was diluted with EtOAc and concentrated onto silica gel. This material was then purified using normal phase column chromatography (24 g silica, 0-5% MeOH in DCM) to give 4-cyclopropyl-l-(5-(3-fluoro-4-methylphenyl)-2-(6-(hydroxymethyl)-5-methylpyridin-2-yl)oxazol-4-yl)pyrimidin-2(17 / )-one (200 mg, 462 pmol, 57.6 %) as a solid.

[0204] (+esi) [M+H]+= 433.1

[0205] ‘H NMR (400 MHz. CDCh) 57.97 (d, 7= 7.8 Hz, 1H), 7.63 (d. J = 7.9 Hz, 1H), 7.57 (d, J = 6.9 Hz, 1H), 7.28 - 7.26 (m, 1H), 7.25 - 7.20 (m, 2H), 6.38 (d, J = 6.9 Hz, 1H), 4.79 (s, 2H), 2.32 (s, 3H), 2.30 (d, J= 1.9 Hz, 3H), 1.96 (tt, J= 8.2, 4.5 Hz, 1H), 1.43 (p, 7= 4.2 Hz, 2H), 1.19 (dq, 7 = 7.5, 4.0 Hz, 2H).(6-(4-(4-cyclopropyl-2-oxopyrimidin-l(2]3)-yl)-5-(3-fluoro-4-methylphenyl)oxazol-2-yl)-3-methylpyridin-2-yl )methyl methanesulfonate

[0206] To a solution of 4-cyclopropyl-l-(5-(3-fluoro-4-methylphenyl)-2-(6-(hydroxymethyl)-5-methylpyridin-2-yl)oxazol-4-yl)pyrimidin-2( 1 H)-one (200 mg, 1 Eq, 462 pmol) in DCM (2.0 mb) were added triethylamine (234 mg, 322 pL, 5 Eq, 2.31 mmol) and methanesulfonicanhydride (208 mg, 2.5 Eq, 1.16 mmol). The mixture was stirred at 22 °C for 2 hours. The reaction mixture was quenched by the addition of water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by normal phase chromatography (12 g silica gel, 0-100% EtOAc in hexanes, then 100% DCM) to afford (6-(4-(4-cyclopropyl-2-oxopyrimidin-l(2H)-yl)-5-(3-fluoro-4-methylphenyl)oxazol-2-yl)-3-methylpyridin-2-yl)methyl methanesulfonate (145 mg, 284 pmol, 61%) as a solid.

[0207] (+esi) [M+H]+= 511.1

[0208] NMR (400 MHz, CDCh) 58.08 (d, 7= 8.0 Hz, 1H), 7.74 (d, 7= 8.0 Hz, 1H), 7.59 (d, 7= 6.9 Hz, 1H), 7.30 (s, 1H), 7.26 (d, 7= 5.2 Hz, 2H), 6.41 (d, 7= 6.9 Hz, 1H), 5.52 (s, 2H), 3.20 (s. 3H), 2.55 (s. 3H). 2.33 (d, 7= 1.9 Hz. 3H), 1.99 (dt, 7= 8.0, 3.6 Hz, 1H), 1.45 (t, 7= 3.8 Hz, 2H), 1.23 (dq, 7 = 7.7, 4.1 Hz, 2H).Atty. Docket: UCSF-849WOl-(2-(6-(bromomethyl)-5-methylpyridin-2-yl)-5-(3-fluoro-4-methylphenyl)oxazol-4-yl)-4-cyclop ropylpyrimidin-2 (l A)-one

[0209] To a stirred solution of (6-(4-(4-cyclopropyl-2-oxopyrimidin-l(2H)-yl)-5-(3-fluoro-4-methylphenyl)oxazol-2-yl)-3-methylpyridin-2-yl)methyl methanesulfonate (145 mg, 1 Eq, 284 pmol) in THF (2 mL) was added lithium bromide trihydrate (400 mg, 10 Eq, 2.84 mmol) and the reaction was heated at 50 °C for 4 hours. The reaction was cooled to room temperature and concentrated under reduced pressure. Saturated aqueous ammonium chloride was added to the residue and the aqueous layer was extracted four times with DCM. The organic extracts were combined, dried over MgSO i, filtered, and concentrated down under reduced pressure to give crude material. This material and purified by normal phase chromatography (12 g silica gel, 0-100% EtOAc in hexanes) to afford l-(2-(6-(bromomethyl)-5-methylpyridin-2-yl)-5-(3-fluoro-4-methylphenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(l / / )-one (75 mg, 0.15 mmol, 53%) as a solid.

[0210] (+esi) [M+H]+= 495.0

[0211] ‘H NMR (400 MHz, CDCh) 57.97 (d, J= 7.9 Hz, 1H), 7.66 (d, J = 7.9 Hz, 1H), 7.58 (d, J = 6.9 Hz, 1 H), 7.29 (d, J = 10.2 Hz, 1 H), 7.23 (d, J = 5.7 Hz, 2H), 6.36 (d, J = 6.9 Hz, 1 H), 4.70 (s, 2H), 2.52 (s, 3H), 2.30 (s, 3H), 2.03 - 1.96 (m, 1H), 1.45 - 1.39 (m, 2H), 1.24 - 1.17 (m, 2H).4-cyclopropyl-l-{2-[6-((fluoro-lsF}methyl}-5-methyl-2-pyridyl]-5-(3-fluoro-4-tolyl -l,3-oxazol-4-yl}-2( IFF-pyrimidinone [CompoundI8F-376]

[0212] A solution of K18F in H218O (3 mL, 486 mCi) was loaded onto a QMA cartridge (waters, WAT023525) that had been prepped by washing with 5 mL of 1 M sodium carbonate followed by 10 mL of type 1 water. Once loaded, the K18F was eluted from the cartridge with 1 mL of eluting solution (50% MeCN in type 1 water, 1 mg / mL potassium carbonate. 6.2 mg / mL Kryptofix [2.2.2.]). The K18F solution was then concentrated under vacuum with a positive pressure of nitrogen. Dry MeCN was added to the dried material and the solution was concentrated under vacuum with a positive pressure of nitrogen. This process was repeated 4 times. Once dry, the K18F residue measured 438 mCi of activity. To the residue was added l-(2-(6-(bromomethyl)-5-methylpyridin-2-yl)-5-(3-fluoro-4-methylphenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(l / 7)-one (2.6 mg, solution in 250 pL of DMSO) and the reaction was sealed and heated at 90 °C for 10 minutes. After 10 minutes, the activity of the solution was 410Atty. Docket: UCSF-849WOmCi. The crude reaction was mixed with an additional 250 pL of DMSO and directly injected onto a semi-prep HPLC column (Luna 5u Cl 8(2)). The mixture was eluted at 4 mL / min using 10% MeCN in water for 13.5 minutes. During this time, unreacted K18F eluted with 225 mCi of activity. At 13.5 minutes, the elution solution was changed to 90% MeCN in water. The product eluted at 24 minutes with 12.1 mCi of activity in 2 mL of solvent. This solution was mixed with 25 mL of type 1 water and loaded onto a C18 cartridge (5 mL / min using a syringe pump, waters. WAT023501) that had been prepped by rinsing with 5 mL of EtOH followed by 10 mL of type 1 water. Once loaded, the product was eluted from the Cl 8 cartridge using 0.50 mL of absolute EtOH. The first 150 pL of EtOH was discarded and the second 350 pL of EtOH was collected to give 4-cyclopropyL 1 - { 2- [6- ((fluoro-18F)methyl)-5-methyl-2-pyridyl] -5- (3-fluoro-4-tolyl)- 1,3-oxazol-4-yl}-2(lH)-pyrimidinone (solution in 0.35 mL of EtOH, 9.8 mCi, 2.2% radiochemical yield (uncorrected)). The identity and purity of the product was confirmed by co-injection of 1 pL of the product solution with 5 pL of a 10 mM solution of 4-cyclopropyl-l-{2-[6-((fluoro-18F)methyl)-5-methyl-2-pyridyl]-5-(3-fluoro-4-tolyl)-l,3-oxazol-4-yl}-2(lH)-pyrimidinone onto an analytical HPLC (100 mm Luna 5u C18(2) column, 60% MeCN in water with 0.1% formic acid). The product eluted at 9.2 minutes with overlap of the RAD and UV signals. Single injection of 1 pL of the product solution (100 mm Luna 5u C18(2) column, 60% MeCN in water with 0.1% formic acid) gave >99% radiochemical purity of 4-cyclopropyL l-(5-(3-fluoro-4-methy lphenyl)-2-(6-(( fluoro-187r)methyl)-5-methylpyridin-2-yl)oxazol-4-yl)pyrimidin-2( 1H)-one.Atty. Docket: UCSF-849WOFirst Compound Syntheses Compound 24: l-(5-(4-chloro-3-fluorophenyl)-2-(6-fluoro-4-methylpyridin-2-yl)oxazol-4-yl)- 4-cyclopropylpyrimidin-2( lH)-onel-(4-chloro-3-fluorophenyl)-2,2-dihydroxyethan-l-one

[0213] To a stirred solution of l-(4-chloro-3-fluorophenyl)ethan-l-one (100 g. 1 Eq, 579 mmol) in DMSO (1000 mL) was added hydrobromic acid (141 g, 94.4 L, 3.0 Eq. 1.74 mol, 48% in water). The reaction mixture was stirred at 25 °C for 2 hours followed by stirring at 50 °C for 16 hours. The reaction mixture was cooled to 0 °C and ice-cold water was added. The solid precipitate was collected by vacuum filtration, washed with hexanes, and dried at 50 °C to afford l-(4-chloro-3-fluorophenyl)-2,2-dihydroxyethan-l-one (75.0 g, 0.370 mol, 63 %) as a solid.

[0214] 1H NMR (400 MHz. DMSO) 88.00 (dd, J = 10.2, 1.9 Hz, 1H), 7.97 - 7.84 (m, 1H), 7.83 - 7.68 (m, 1H), 6.97 (d, J = 6.7 Hz, 2H), 5.62 (d, J = 5.5 Hz, 1H).N-(2-(4-chloro-3-fluorophenyl.)-Fhydroxy-2-oxoethyl)fbrmamide

[0215] To a stirred solution of l-(4-chloro-3-fluorophenyl)-2,2-dihydroxyethan-l-one (75.0 g, 1 Eq, 367 mmol) in 1,4-Dioxane (750 mL) was added formamide (66.0 g. 58.4 mL, 4.0 Eq, 1.47 mol) and the resulting reaction mixture was heated at 90 °C for 2 h. The reaction was allowed to cool to room temperature and the dioxane was removed under reduced pressure. The resulting residue was poured into ice-cold water and the obtained precipitate was collected by vacuum filtration. The solid was dissolved in ethyl acetate, dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure. The obtained solid was triturated with MTBE (100 mL), filtered, washed with MTBE, and dried under reduced pressure to afford A-(2-(4-chloro-3-fhiorophenyl)-l-hydroxy-2-oxoethyl)formamide (65.0 g, 0.280 mol, 77%) as a solid.Atty. Docket: UCSF-849WO

[0216] ’H NMR (400 MHz, DMSO) 88.99 (d, J = 8.6 Hz, 1H), 8.12 - 8.05 (m, 1H), 7.92 (dd, J = 10.0, 1.8 Hz, 1H), 7.88 - 7.75 (m, 2H), 6.87 (dd, J= 7.0, 5.2 Hz, 1H), 6.32 (t, J = 7.9 Hz, 1H). N-(l-chloro-2-(4-chloro-3-fluorophenyl)-2-oxoethyl)fomamide

[0217] To a stirred solution of N-(2-(4-chloro-3-fluorophenyl)-1-hydroxy-2-oxoethyl)formamide (10.0 g, 1 Eq, 43.2 mmol) in dichloromethane (100 mL) was added phosphorus pentachloride (10.8 g, 1.2 Eq, 51.8 mmol) under nitrogen at 0 °C and the reaction mixture was stirred at 0 °C. The reaction mixture was then allowed to warm to room temperature and stirred at temperature for 3 hours. The solvent was removed under reduced pressure to give crude solid compound, which was then triturated with hexanes, filtered, and dried under reduced pressure to afford N-(1-chloro-2-(4-chloro-3-fluorophenyl)-2-oxoethyl)formamide (10.2 g, 40.8 mmol, 94.5 %) as a solid. This compound was directly used in the next step without characterization due to its instability.N-(2-(4-chloro-3-fluorophenyl)-1-(4-cyclopropyl-2-oxopyrimidin-1(2H)-yl)-2-oxoethyl)formamide

[0218] To a solution of 4-cyclopropylpyrimidin-2(1H)-one (5.00 g, 1 Eq, 36.7 mmol) in N, N- dimethylformamide (50 mL) and triethylamine (1 1.2 g, 15.4 mL, 3.0 Eq, 110 mmol) was added a solution of N-(1-chloro-2-(4-chloro-3-fluorophenyl)-2-oxoethyl)formamide (10.1 g, 1.1 Eq. 40.4 mmol) in DMF (30 mL) at room temperature under nitrogen. The resulting reaction mixture was stirred at room temperature for 16 hours. Water was added to the reaction mixture which was then extracted with ethyl acetate (3x 100 mL). The combined organic layers were washed with brine, dried over sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was triturated with diethyl ether, collected by vacuum filtration, washed with diethyl ether, and dried under reduced pressure to afford N-(2-(4-chloro-3-fluorophenyl)-1-(4-cyclopropyl-2-oxopyrimidin-1(2H)-yl)-2-oxoethyl)formamide (7.30 g, 21.0 mmol, 57%) as a solid.

[0219] 1H NMR (400 MHz, DMSO-d6) ppm 9.62 (d, J = 8.16 Hz, 1 H), 8.22 (s, 1 H), 8.17 (d, J = 6.97 Hz, 1H), 7.77 - 7.86 (m, 2 H), 7.68 (dd, J = 8.42, 1.84 Hz, 1 H), 7.21 (d, J = 8.16 Hz, 1 H), 6.57 (d, J = 6.97 Hz, 1 H), 1.93 - 2.01 (m, 1 H), 1.02 - 1.10 (m, 2 H), 0.95 - 1.01 (m, 2 H).Atty. Docket: UCSF-849WO1-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one

[0220] N-(2-(4-chloro-3-fluorophenyl)-l-(4-cyclopropyl-2-oxopyrimidin-l(2H)-yl)-2-oxoethyl)forniamide (3.50 g, 1 Eq, 10.0 mmol) was suspended in Eaton’s reagent (7.5% phosphorus(V) oxide in methanesulfonic acid, 36.0 g, 24.0 mL, 15 Eq, 0.150 mol) and the mixture was heated to 60 °C for 2 hours. The reaction mixture was poured into ice and basified with solid sodium bicarbonate. The mixture was then extracted with DCM (3 x 100 mL) and the combined organic layers were washed with brine, dried over sodium sulfate, and concentrated under reduced pressure to give crude product. This material was then purified by normal phase chromatography (45 g silica gel, 1-2% MeOH in chloroform). The fractions containing product were evaporated to give a crude solid. This material was then triturated with MTBE, collected by vacuum filtration, and dried under reduced pressure to afford l-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(T / - / )-one (650 mg. 1.96 mmol, 20%) as a solid.

[0221] 1H NMR (400 MHz, DMSO-d6) δ ppm 8.69 - 8.73 (m, 1 H), 8.08 (d, J = 6.97 Hz, 1 H), 7.71 - 7.77 (m, 1 H), 7.43 - 7.49 (m, 1 H), 7.22 (dt, J = 8.42, 0.85 Hz, 1 H), 6.63 - 6.68 (m, 1 H) 2.06 - 2.16 (m, 1 H), 1.13 - 1.18 (m, 4 H).

[0222] (+esi)[M+H]=332.21-(5-(4-chloro-3-fluorophenyl)-2-(6-fluoro-4-methylpyridin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one

[0223] To a resealable vial were added 1-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (0.030 g, 1 Eq, 0.090 mmol), 2-bromo-6-fluoro-4-methylpyridine (21 mg, 1.2 Eq. 0.11 mmol), bromo(l,10-phenanthroline)(triphenylphosphine) copper(I) (8.0 mg, 0.15 Eq, 14 pmol), Pd(OAc)2 (3.1 mg, 0.15 Eq, 14 pmol), dicyclohexyl(2',6'-diisopropoxy-[l,l'-biphenyl]-2-yl)phosphane (8.4 mg, 0.20 Eq, 18 pmol), and K2CO3 (38 mg, 3 Eq, 0.27 mmol). Dioxane (1.0 mL) was added, and the vial was capped, purged with nitrogen for 5 minutes, and heated at 130 °C for 20 hours. The crude mixture was concentrated onto silica gel and directly purified by normal phase chromatography (12 g silica gel column, 0-5% MeOH / DCM) to afford l-(5-(4-chloro-3-fluorophenyl)-2-(6-fluoro-4-methylpyridin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one (18.8 mg, 42.6 pmol, 47%) as a solid.

[0224] LCMS (M+H)+ = 441.0. LCAP % at 280 nm > 95%.Atty. Docket: UCSF-849WO

[0225] ’H NMR (400 MHz, Methanol-d4) 57.92 (s, 1H), 7.80 (d, J = 6.9 Hz, 1H), 7.51 - 7.46 (m, 2H), 7.31 (dd, J = 8.5, 2.0 Hz, 1H), 7.00 (s, 1H), 6.56 (d, J = 6.9 Hz, 1H), 2.53 (s, 3H), 2.05 (qd, 1H), 1.37 (p, J = 4.3 Hz, 2H), 1.27 (dq, J = 9.8, 7.9, 5.8 Hz, 2H).Compound 77: 1-(5-(4-chloro-3-fluorophenyl)-2-(2-methylbenzo[d]oxazol-6-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-onePd(OAc)2, RuPhos, K2CO3pivalic acid, molecular sieves1-(5-(4-chloro-3-fluorophenyl)-2-(2-methylbenzo[d]oxazol-6-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one:

[0226] To a resealable vial were added l-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2( l / 7)-one (0.050 g, 1 Eq, 0.15 mmol), 6-bromo-2-methyl-3a,7a-dihydrobenzo [7] oxazole (48 mg, 1.5 Eq, 0.225 mmol), pivalic acid (6.2 mg, 0.40 Eq, 60 pmol), Pd(OAc)2 (3.4 mg, 0.10 Eq, 15 pmol), dicyclohexyl(2',6'-diisopropoxy-[l,l'-biphenyl]-2-yl)phosphane (14 mg, 0.20 Eq, 30 pmol), 4 angstrom molecular sieves (100 mg), K2CO3 (62 mg, 3 Eq, 0.45 mmol), and toluene (2.0 mL). The vial was capped, purged with nitrogen for 5 minutes, and heated at 110 °C for 16 hours. The crude reaction was directly purified by normal phase chromatography (24 g silica gel column, 0-5% MeOH in DCM) to afford 1-(5-(4-chloro-3-fluorophenyl)-2-(2-methylbenzo[d]oxazol-6-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (16.7 mg, 36.1 pmol, 24 %) as yellow solid.

[0227] LCMS (M+H)+ = 463.1. LCAP % at 280 nm 97%.

[0228] ’H NMR (400 MHz, MeOD) 58.38 (s, 1H), 8.19 (d, J= 8.4 Hz, 1H), 8.10 (d, J= 6.9 Hz, 1H), 7.80 (d, 7= 8.4 Hz, 1H), 7.62 (t, J = 8.0 Hz, 1H), 7.53 (dd, 7= 10.1, 2.0 Hz, 1H), 7.35 (d, 7 = 8.5 Hz, 1H), 6.74 (d, 7= 6.9 Hz, 1H), 2.72 (s, 3H), 2.20 - 2.13 (m, 1H), 1.38 - 1.25 (m. 4H).Atty. Docket: UCSF-849WOCompound 498: 1-(5-(4-chloro-3-fluorophenyl)-2-(7-methylpyrazolo[1,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-onePd(dppf), Cui, CS2CO31-(5-(4-chloro-3-fluorophenyl)-2-(7-methylpyrazolo[1,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one:

[0229] To a resealable vial were added 1-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (0.050 g, 1 Eq, 0.15 mmol), 2-bromo-7-methylpyrazolo[1,5-a]pyrimidine (48 mg, 1.5 Eq, 0.23 mmol), CS2CO3 (0.15 g. 3.0 Eq, 0.45 mmol), Cui (4.3 mg, 0.15 Eq, 23 pmol), Pd(dppf)C12 (17 mg, 0.15 Eq, 23 pmol), and DMF (2.0 mL). The vial was capped, purged with nitrogen for 5 minutes, and heated at 90 °C for 2.5 hours. The crude mixture was diluted with brine, extracted with EtOAc (2 x 10 mL), and the organic phase was concentrated onto Celite. This material was then purified with normal phase chromatography (24 g silica gel column, 0-5% MeOH / DCM) to afford 1-(5-(4-chloro-3-fluorophenyl)-2-(7-methylpyrazolo[1,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (6.2 mg, 13 pmol, 8.9%) as a solid.

[0230] LCMS (M+H)+ = 463.1. LCAP % at 280 nm 98%.

[0231] NMR (400 MHz. MeOD) 88.55 (d, J = 4.3 Hz, 1H), 8.13 (d, J= 6.9 Hz, 1H), 7.64 (t, J= 8.0 Hz, 1H), 7.56 (dd. J= 10.1. 1.9 Hz, 1H), 7.38 (d, J = 10.1 Hz. 2H), 7.10 (d, 7 = 4.3 Hz, 1H), 6.75 (d, 7= 6.9 Hz, 1H), 2.92 (s, 3H), 2.17 (d, 7= 8.4 Hz, 1H), 1.33 (dt, 7 = 19.6, 4.9 Hz, 4H).Atty. Docket: UCSF-849WOCompound 499: 1-(5-(4-chloro-3-fluorophenyl)-2-(5,7-dimethylpyrazolo[1,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one1-(5-(4-chloro-3-fluorophenyl)-2-(5,7-dimethylpyrazolo[1,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one

[0232] To a resealable vial were added 1-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (0.050 g, 1 Eq, 0.15 mmol), 2-bromo-5,7-dimethylpyrazolo[1,5-a]pyrimidine (51 mg, 1.5 Eq, 0.23 mmol), pivalic acid (6.2 mg, 0.40 Eq, 60 pmol), Pd(OAc)2 (3.4 mg, 0.10 Eq, 15 pmol), dicyclohexyl(2',6'-diisopropoxy-[l,l'-biphenyl]-2-yl)phosphane (14 mg, 0.20 Eq, 30 pmol), and K2CO3 (62 mg, 3 Eq, 0.45 mmol). Toluene (3.0 mL) was added, and the vial was capped, purged with nitrogen for 5 minutes, and heated at 110 °C for 16 hours. The crude mixture was concentrated onto silica gel and directly purified by normal phase chromatography (12 g silica gel column, 0-5% MeOH / DCM) to afford 1-(5-(4-chloro-3-fluorophenyl)-2-(5,7-dimethylpyrazolo[1,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (18.8 mg, 42.6 pmol, 47%) as a solid.

[0233] LCMS (M+H)+ = 477.0. LCAP % at 280 nm > 95%.

[0234] ’H NMR (400 MHz, Methanol-d4) 88.02 (d, J = 6.9 Hz, 1H), 7.62 - 7.54 (m, 1H), 7.52 (dd, J = 9.9, 2.0 Hz, 1H), 7.36 (ddd, J = 8.4, 2.1, 0.9 Hz, 1H), 7.19 (s, 1H), 6.96 (d, J= 1.1 Hz, 1H), 6.69 (d, J = 6.9 Hz, 1H). 2.86 (d, J = 0.9 Hz. 3H), 2.63 (s, 3H). 2.12 (tt, J= 8.3, 4.6 Hz, 1H), 1.33 (ddt, J = 27.6, 6.2, 3.9 Hz, 4H).Atty. Docket: UCSF-849WOCompound 500: 1-(5-(4-chloro-3-fluorophenyl)-2-(7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-onePd(OAc)2, RuPhos, K2CO3pivalic acid, molecular sieves1-(5-(4-chloro-3-fluorophenyl)-2-(7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one:

[0235] To aresealable vial were added l-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (0.050 g, 1 Eq, 0.15 mmol), 2-bromo-7-(trifluoromethyl)pyrazolo[l,5-a]pyrimidine (60 mg, 1.5 Eq, 0.23 mmol), pivalic acid (6.2 mg, 0.40 Eq, 60 pmol), Pd(OAc)2 (5.1 mg, 0.15 Eq, 23 pmol), dicyclohexyl(2',6'-diisopropoxy-[l,l'-biphenyl]-2-yl)phosphane (18 mg, 0.25 Eq, 38 pmol), 4 angstrom molecular sieves (100 mg), K2CO3 (62 mg, 3 Eq, 0.45 mmol), and toluene (3.0 mL). The vial was capped, purged with nitrogen for 5 minutes, and heated at 110 °C for 16 hours. The crude mixture was directly purified by normal phase chromatography (24 g silica gel column, 0-5% MeOH / DCM) to afford crude product. This material was then triturated in warm MeOH. The solid was collected by filtration and dried to afford 1-(5-(4-chloro-3-fluorophenyl)-2-(7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (11.2 mg, 21.7 pmol, 14 %) as a solid.

[0236] LCMS (M+H)+= 517.1. LCAP % at 280 nm 96%.

[0237] NMR (400 MHz, MeOD) 88.83 (d, J = 4.2 Hz, 1H), 8.13 (d, J= 6.9 Hz, 1H), 7.68 -7.59 (m, 3H), 7.55 (dd, J= 10.0, 2.1 Hz, 1H), 7.44 - 7.37 (m, 1H), 6.76 (d, 7= 6.9 Hz, 1H). 2.17 (ddd, J = 12.8, 7.8, 4.6 Hz, 1H), 1.42 - 1.26 (m, 4H).Atty. Docket: UCSF-849WOCompound 501: l-(5-(4-chloro-3-fluorophenyl)-2-(4,6-dimethylpyrazolo[l,5-a]pyrazin-2-yl )oxazol-4-yl )-4-cyclopropylpyrimidin-2 (IH)-onel-(5-(4-chloro-3-fluorophenyl)-2-(4,6-dimethylpyrazolo[l,5-a]pyrazin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2( l / / )-one:

[0238] To a resealable vial were added 1-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (0.050 g, 1 Eq, 0.15 mmol), 2-bromo-4,6-dimethylpyrazolo[1,5-a]pyrazine (51 mg, 1.5 Eq, 0.23 mmol), CS2CO3 (0.15 g. 3.0 Eq, 0.45 mmol), Cui (4.3 mg, 0.15 Eq, 23 pmol), Pd(dppf)Ch (17 mg, 0.15 Eq, 23 pmol), and DMF (3.0 mL). The vial was capped, purged with nitrogen for 5 minutes, and heated at 90 °C for 2.5 hours. The crude mixture was diluted with brine, extracted with EtOAc (2 x 10 mL), and the organic layer was concentrated onto Celite. This material was purified with normal phase chromatography (24 g silica gel column, 0-5% MeOH / DCM) to afford 1-(5-(4-chloro-3-fluorophenyl)-2-(4,6-dimethylpyrazolo[1,5-a]pyrazin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one (18.4 mg, 38.6 pmol, 26%) as a solid.

[0239] LCMS (M+H)+= 477.0. LCAP % at 280 nm > 95%.

[0240] NMR (400 MHz. MeOD) 88.42 (s, 1H), 8.12 (d, J =6.9 Hz, 1H), 7.68 - 7.59 (m, 2H), 7.54 (dd, J= 10.0, 2.0 Hz. 1H), 7.39 - 7.31 (m, 1H), 6.76 (d. J= 6.9 Hz, 1H). 2.83 (s, 3H), 2.55 (s, 3H), 2.17 (dt, J = 8.4, 3.6 Hz, 1H), 1.39 - 1.26 (m, 4H).Atty. Docket: UCSF-849WOCompound 502: 1-(5-(4-chloro-3-fluorophenyl)-2-(isoquinolin-3-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-onel-[5-(4-chloro-3-fluorophenyl)-2-(isoquinolin-3-yl)-l,3-oxazol-4-yl]-4-cyclopropyl-l,2-dihydropyrimidin-2-one:

[0241] Under inert atmosphere, 1-[5-(4-chloro-3-fluorophenyl)-1,3-oxazol-4-yl]-4-cyclopropyl-1,2-dihydropyrimidin-2-one (0.080 g, 0.241 mmol, 1.0 eq), potassium carbonate (0.10 g, 0.723 mmol, 3.0 eq), bromo(l,10-phenanthroline)(triphenylphosphine)copper(I) (0.021 g, 0.036 mmol, 0.15 eq), RuPhos (0.023 g, 0.048 mmol, 0.2 eq), and 3-bromoisoquinoline (0.075 g, 0.362 mmol, 1.5 eq) were suspended in dioxane (1.6 mL). The resulting mixture was purged with Ar for 5 minutes prior to the addition of palladium(II) acetate (0.0080 g, 0.036 mmol. 0.15 eq). The reaction vial was sealed, and the reaction mixture was stirred at 120 °C for 2.5 hours. After cooling to room temperature, the reaction mixture was diluted with dichloromethane and filtered through a pad of celite. The celite pad was washed with a mixture of dichloromethane and methanol (9 / 1, v / v). The filtrate was concentrated under reduced pressure to give the crude product. The crude product was purified via normal phase column chromatography (0-4% MeOH in DCM). Fractions containing the desired product were concentrated under reduced pressure. The residue was triturated with methanol, collected by filtration, washed with methanol, and dried under reduced pressure to give 1-[5-(4-chloro-3-fluorophenyl)-2-(isoquinolin-3-yl)-1,3-oxazol-4-yl]-4-cyclopropyl-1,2-dihydropyrimidin-2-one (0.056 g, 0.121 mmol, 50%).

[0242] LC-MS: 2.63 min, [M+H]+= 459.1, 99.0% @ 210 nm

[0243] ‘H NMR (300 MHz. DMSO-t / 6) 59.51 (d. J = 1.1 Hz, 1H), 8.85 (s, 1H), 8.28 (d, J= 8.1 Hz, 1H), 8.25 - 8.17 (m, 2H), 8.01 - 7.88 (m, 1H), 7.88 - 7.84 (m, 1H), 7.84 - 7.74 (m, 1H),Atty. Docket: UCSF-849WO7.63 (dd, 7= 10.2, 2.0 Hz, 1 H), 7.41 - 7.18 (m, 1 H), 6.73 (d, J = 6.9 Hz, 1 H), 2.20 - 2.05 (m, 1H), 1.24- 1.09 (m, 4H).Compound 516: 1-(5-(4-chloro-3-fluorophenyl)-2-(7-(fluoromethyl)-5-methylpyrazolo[1,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(1H)-one{2-bromo-5-methylpyrazolo[1,5-a]pyrimidin-7-yl}methanol:

[0244] Ethyl 2-bromo-5-methylpyrazolo[l,5-a]pyrimidine-7-carboxylate (1.10 g, 3.87 mmol, 1.0 eq) was dissolved in a mixture of anhydrous tetrahydrofuran (11 mL) and anhydrous methanol (11 mL). The resulting mixture was cooled to -4 °C and then sodium borohydride (0.146 g, 3.87 mmol, 1.0 eq) was added. The reaction solution was stirred at -4 °C for 1 hour. The reaction was quenched with water and then extracted with EtOAc (3 x). The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The crude material was triturated with diethyl ether, filtered and dried to yield {2-bromo-5-methylpyrazolo[1,5-a]pyrimidin-7-yl}methanol (0.370 g, 1.53 mmol, 39%).

[0245] ‘H NMR (300 MHz. DMSO-t / 6) 57.02 (s, 1H), 6.78 (s. 1H), 5.95 (t, J = 5.8 Hz, 1H), 4.89 (d,.7= 5.8 Hz, 2H), 2.56 (s, 3H).2-bromo-7-{ [(tert-bu tyldimethylsilyl)oxy]methyl }-5-methylpyrazolo[ 1,5-a]pyrimidine:

[0246] 2,6-Lutidine (0.328 g, 0.355 mL, 3.06 mmol, 2.0 eq) was added to a solution of {2-bromo-5-methylpyrazolo[1,5-a]pyrimidin-7-yl}methanol (0.370 g, 1.53 mmol, 1.0 eq) in anhydrous dichloromethane (3.7 mL) at 0 °C. The resulting mixture was stirred for 5 minutes; then, tert-butyldimethylsilyl trifluoromethanesulfonate (0.848 g, 3.21 mmol, 2.1 eq) was addedAtty. Docket: UCSF-849WOdropwise. The mixture was then stirred at room temperature for 16 hours. The reaction was quenched with water and diluted with dichloromethane. Then, aqueous solution of citric acid (10%. w / w) was added, and the mixture was extracted with dichloromethane (3x). The combined organic extracts were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The crude material was purified by normal phase column chromatography (0-20% EtOAc in cyclohexane) to give 2-bromo-7-{[(tert-butyldimethylsilyl)oxy]methyl}-5-methylpyrazolo[1,5-a]pyrimidine (0.314 g, 0.881 mmol, 58%).

[0247] NMR (300 MHz, DMSO-76) 56.92 (s, 1H), 6.80 (s, 1H), 5.09 (d, J = 1.3 Hz, 2H), 2.57 (s, 3H), 0.96 (s. 9H), 0.18 (s, 6H).l-[2-(7-{[(tert-butyldimethylsilyl)oxy]methyl}-5-methylpyrazolo[l,5-a]pyrimidin-2-yl)-5-(4-chloro-3-fluorophenyl)- 1,3-oxazol-4-yl] -4-cyclopropyl- 1,2-dihydropyrimidin-2-one:

[0248] l-(5-(4-Chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2( lH)-one (0.300 g, 0.904 mmol, 1.0 eq), 2-bromo-7-{[(tert-butyldimethylsilyl)oxy]methyl}-5-methylpyrazolo[1,5-a]pyrimidine (0.314 g, 0.882 mmol, 1.0 eq), potassium carbonate (0.375 g, 2.71 mmol, 3.0 eq), RuPhos (0.084 g, 0.181 mmol, 0.2 eq), and bromo(1,10-phenanthroline)(triphenylphosphine)copper(I) (0.079 g, 0.136 mmol, 0.15 eq) were suspended in anhydrous 1,4-dioxane (7.5 mL). The resulting mixture was purged with Ar for 5 minutes prior to the addition of palladium(II) acetate (0.030 g, 0.136 mmol, 0.15 eq). The reaction vial was sealed, and the reaction mixture was stirred at 100 °C for 4 hours. Brine was added, and the mixture was extracted with dichloromethane (3 x). The combined organic layers were dried over Na2SO4 and concentrated under reduced pressure. The crude material was purified by normal phase column chromatography (0-30% EtOAc in DCM). The purest fractions were concentrated separately from the impure fractions, which were triturated with methanol. The solid material was filtered, dried and combined with the purest fractions to give 1-[2-(7-{[(tert-butyldimethylsilyl)oxy]methyl}-5-methylpyrazolo[1,5-a]pyrimidin-2-yl)-5-(4-chloro-3-fluorophenyl)-1,3-oxazol-4-yl]-4-cyclopropyl-1,2-dihydropyrimidin-2-one (0.125 g. 0.202 mmol, 20%).

[0249] NMR (300 MHz, DMSO-^) 58.18 (d, 7= 6.9 Hz, 1H), 7.82 - 7.74 (m, 1H), 7.61 (dd, 7= 10.2, 2.0 Hz, 1H), 7.36 (s. 1H), 7.34-7.29 (m, 1H), 7.07 (s, 1H), 6.71 (d, 7= 7.0 Hz, 1H), 5.21 (s. 2H), 2.63 (s. 3H). 2.17 - 2.08 (m, 1H), 1.22 - 1.12 (m, 4H). 0.98 (s, 9H), 0.22 (s, 6H).Atty. Docket: UCSF-849WOl-[5-(4-chloro-3-fluorophenyl)-2-[7-(hydroxymethyl)-5-methylpyrazolo[l,5-a]pyrimidin-2-yl]-l,3-oxazol-4-yl]-4-cydopropyl-l,2-dihydropyrimidin-2-one:

[0250] A mixture of l-[2-(7-{[(terLbutyldimethylsilyl)oxy]methyl}-5-methylpyrazolo[l,5-a]pyrimidin-2-yl)-5-(4-chloro-3-fluorophenyl)-l,3-oxazol-4-yl]-4-cyclopropyl-l,2-dihydropyrimidin-2-one (0.098 g, 0.161 mmol, 1.0 eq) in tetrahydrofuran (3.9 mL) was cooled to 0 °C. To this, a 1.0 M solution of tetrabutylammonium fluoride in tetrahydrofuran (0.063 g, 0.242 mL, 0.242 mmol, 1.5 eq) was added. The resulting mixture was stirred at 0 °C for 30 minutes. The reaction was quenched by the addition of saturated ammonium chloride solution and extracted with diethyl ether (3 x). During the extraction, precipitation was observed. The solid was collected by filtration and combined with the concentrated organic layers. The crude material was then purified by normal phase column chromatography (0-4% MeOH in DCM) to give l-[5-(4-chloro-3-fluorophenyl)-2-[7-(hydroxymethyl)-5-methylpyrazolo[l,5-a]pyrimidin-2-yl]-l,3-oxazol-4-yl]-4-cyclopropyl-l,2-dihydropyrimidin-2-one (0.027 g, 0.055 mmol, 32.7%).

[0251] LC-MS: 3.55 min, [M+H]+= 493.11, 97.6% @ 220 nm

[0252] ‘H NMR (300 MHz. DMSO-t / 6) 58.19 (d. J= 6.9 Hz, 1H), 7.83 - 7.73 (m. 1H), 7.61 (dd. J = 10.2, 2.0 Hz, 1 H), 7.35 - 7.30 (m, 2H), 7.16 (s, I H), 6.71 (d, J = 6.9 Hz, 1 H), 6.00 (t, J = 5.7 Hz, 1H), 5.02 (d, J = 5.9 Hz, 2H), 2.62 (s, 3H), 2.20 - 2.07 (m, 1H), 1.21 - 1.12 (m, 4H).l-(5-(4-chloro-3-fluorophenyl)-2-(7-(fluoromethyl)-5-methylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one:

[0253] In a 4-mL vial charged with l-(5-(4-chloro-3-fluorophenyl)-2-(7-(hydroxymethyl)-5-methylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one (15 mg, 0.03 mmol, 1.0 equiv.) and THF (0.3 mL) was added DAST (10 mg, 0.06 mmol, 2.0 equiv.). The resulting mixture was allowed to stir at room temperature for 6 hours. At the conclusion of the reaction, all volatiles were removed, and the resulting solid was re-dissolved in DMF. This solution was submitted to reverse phase chromatography (Cl 8 column, 10-100% MeCN in water with 0.1% TFA) to give l-(5-(4-chloro-3-fhiorophenyl)-2-(7-(fluoromethyl)-5-methylpyrazolo[L5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one (3 mg, 20%) as a white solid.

[0254] LCMS (M+H)+= 495.0.Atty. Docket: UCSF-849WO

[0255] ’H NMR (400 MHz, MeOD / CDCh) 87.86 (d, J = 7.0 Hz, 1H), 7.51 (t, J = 8.0 Hz, 1H), 7.44 (dd, J = 9.7, 2.0 Hz, 1H), 7.30 (d, J = 8.2 Hz, 1H), 7.20 (s, 1H), 7.11 (s, 1H), 6.59 (d, J = 6.9 Hz, 1H), 5.96 (d, J = 45.9 Hz, 2H). 2.68 (s, 3H), 2.05 (tt. J = 8.2, 4.5 Hz, 1H), 1.35 (p, J = 4.2 Hz, 2H), 1.29 - 1.22 (m, 2H).Compound 517: l-(5-(4-chloro-3~fluorophenyl)~2-(5~(fluoromethyl)~7-methylpyrazolo[l.,5-a]pyrimidin~2-yl)oxazol~4-yl)-4~cyclopropylpyrimidin-2(lH)~onePd(PPh3)4, Cs2CO3bromo(1,10-phenanthroline)- (triphenylphosphine)copper(l)(2-bromo-7-methylpyrazolo[l,5-a]pyrimidin-5-yl)methanol:

[0256] In a 40-mL vial charged with sodium methoxide (10.0 mg, 0.1 Eq, 185 pmol) and methyl 2-bromo-7-methylpyrazolo[l,5-o,]pyrimidine-5-carboxylate (500 mg, 1 Eq, 1.85 mmol) was added MeOH (10 mL) at room temperature. Then, sodium borohydride (70.0 mg, 1 Eq, 1.85 mmol) was added to the previous mixture over 30 minutes, and the resulting mixture was allowed to stir for another 3 hours at room temperature. At the conclusion of reaction, all volatiles were removed, and the desired product was purified via ISCO silica gel column (0-25% of 3:1 EtOAc to EtOH in DCM) to give (2-bromo-7-methylpyrazolo[l,5-a]pyrimidin-5- yl)methanol (300 mg, 1.24 mmol, 67%) a white solid.

[0257] NMR (400 MHz, CDCh) 86.66 (s, 1H), 6.65 (d, J= 1.1 Hz, 1H), 4.77 (s, 2H), 2.76 (d, 7= 0.9 Hz, 3H).Atty. Docket: UCSF-849WO2-bromo-5-(fluoromethyl)-7-methylpyrazolo[l,5-a]pyrimidine:

[0258] In a 40-mL vial charged with (2-bromo-7-methylpyrazolo[l,5-a]pyrimidin-5-yl)methanol (120 mg, 1 Eq, 496 pmol) and THF (2 mL) was added / V-diethyl- 1,1,1 -trifluoro-14-sulfanamine (160 mg, 123 pL, 2 Eq, 991 pmol) in a dropwise fashion at 0 °C. The resulting mixture was gradually raised to room temperature over 10 minutes and was allowed to stir at the same temperature for 20 minutes. At the conclusion of reaction, all volatiles were removed, and the desired product was purified by preparative HPLC (Cl 8 column, 10-100% MeCN in water with 0.1% TFA) to give 2-bromo-5-(fluoromethyl)-7-methylpyrazolo[l,5-a]pyrimidine (26 mg, 0.11 mmol. 21%) as a white solid.

[0259] 1H NMR: (400 MHz, CDCh) 86.91 (s, 1H), 6.68 (s, 1H), 5.46 (d, J = 46.7 Hz, 2H), 2.81 (d, J = 0.9 Hz, 3H).l-(5-(4-chloro-3-fluorophenyl)-2-(5-(fluoromethyl)-7-methylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(l / / )-one:

[0260] In a 4-mL vial charged with Pd(PPh3)4(13 mg, 0.1 Eq, 11 pmol), cesium carbonate (0.11 g, 3 Eq, 0.33 mmol), bromo(l,10-phenanthroline)(triphenylphosphine)copper (6.5 mg, 0.1 Eq, 11 pmol), l-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2( 177)-one (37 mg, 1 Eq, 0.11 mmol), and 2-bromo-5-(fluoromethyl)-7-methylpyrazolo[l,5-tf]pyrimidine (27 mg, 1 Eq, 0.11 mmol) was added toluene (1.1 mL) under nitrogen atmosphere. The resulting mixture was allowed to stir at 110 °C for 14 hours. At the conclusion of the reaction, all volatiles were removed. The crude material was purified by preparative HPLC (Cl 8 column, 10-100% MeCN in water with 0.1% TFA) to give l-(5-(4-chloro-3-fluorophenyl)-2-(5-(fluoromethyl)-7-methylpyrazolo[l,5-a]pyrimidin-2-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(17 / )-one (7.6 mg, 15 pmol, 14%) as a white solid.

[0261] LCMS (M+H)+= 495.0.

[0262] 1H NMR: (400 MHz, MeOD / CDCh) 87.90 (d. J = 6.8 Hz, 1H), 7.55 - 7.40 (m. 2H), 7.34 - 7.28 (m, 1H), 7.25 (s, 1H), 7.12 (s, 1H), 6.60 (d, J = 6.9 Hz, 1H), 5.49 (d, J = 46.6 Hz, 2H), 2.94-2.87 (m, 3H), 2.11 - 2.00 (m, 1H), 1.35 (p,.7 = 4.2 Hz, 2H), 1.31 - 1.18 (m, 2H).Atty. Docket: UCSF-849WOCompound 377: l-(5-(4-chloro-3-fluorophenyl)-2-(l-methyl-lH-pyrazolo[4,3-b]p ridin-3-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-onePd(OAc)2, RuPhos, K2CO3pivalic acid, molecular sievesl-(5-(4-chloro-3-fluorophenyl)-2-(l-methyl-lH-pyrazolo[4,3-^]pyridin-3-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(l / Z)-one:

[0263] To aresealable vial were added l-(5-(4-chloro-3-fluorophenyl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one (0.050 g, 1 Eq, 0.15 mmol), 3-bromo-l -methyl- 1H-pyrazolo[4,3-b]pyridine (48 mg, 1.5 Eq, 0.23 mmol), pivalic acid (6.2 mg, 0.40 Eq, 60 pmol), Pd(OAc)2 (3.4 mg, 0.10 Eq, 15 pmol), dicyclohexyl(2',6'-diisopropoxy-[l, T-biphenyl]-2-yl)phosphane (14 mg, 0.20 Eq, 30 pmol), 4 angstrom molecular sieves (100 mg), K2CO3 (62 mg, 3 Eq, 0.45 mmol), and toluene (2.0 mL). The vial was capped, purged with nitrogen for 5 minutes, and heated at 110 °C for 16 hours. The crude reaction was concentrated onto Celite and purified by normal phase chromatography (24 g silica gel column, 0-10% MeOH / DCM to afford l-(5-(4-chloro-3-fluorophenyl)-2-( l-methyl-lH-pyrazolo[4,3- / ?]pyridin-3-yl)oxazol-4-yl)-4-cyclopropylpyrimidin-2(lH)-one (22.9 mg, 49.5 pmol, 33%) as a solid.

[0264] LCMS (M+H)+ = 463.1. LCAP % at 280 nm 97%.

[0265] ‘H NMR (400 MHz. MeOD) 58.76 (d, J = 4.3 Hz, 1H), 8.28 (d. J = 7.9 Hz, 1H), 8.19 (d, J = 6.9 Hz, 1 H), 7.67 - 7.56 (m, 3H), 7.40 (d, J = 8.4 Hz, 1 H), 6.76 (d, J = 7.0 Hz, 1 H), 4.30 (s, 3H), 2.16 (d, J = 4.9 Hz, 1H), 1.39 - 1.25 (m, 4H).Atty. Docket: UCSF-849WOSynthesis of Compound 227. 4-c\'(ionr()p\'l-l-l2-(l-meth\l-2-oxo-6-(iuinol\l)-5-lp- (trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone:N-(l -hydroxy-2-oxo-2-(4-( irifluoromeihyl )phenyl)elhyl)formamide

[0266] To a stirred solution of 2,2-dihydroxy-l-(4-(trifluoromethyl)phenyl)ethan-l-one (10.0 g, 1.0 Eq, 45.4 mmol) in 1,4-Dioxane (150 mL) was added formamide (2.46 g, 2.17 mL, 1.2 Eq, 54.5 mmol) and the resulting reaction mixture was heated at 90 °C for 8 h. The reaction was allowed to cool to room temperature and the dioxane was removed under reduced pressure. The resulting residue was poured into ice-cold water and the obtained precipitate was collected by vacuum filtration. The solid was dissolved in ethyl acetate, dried over anhydrous sodium sulfate, filtered, and evaporated under reduced pressure. The obtained solid was triturated with MTBE (100 mL), filtered, washed with MTBE, and dried under reduced pressure to afford N-(l- hydroxy-2-oxo-2-(4-(trifhioromethyl)phenyl)ethyl)formamide (9.82 g, 39.7 mmol, 87.5%) as a solid.

[0267] 1H NMR (400 MHz, CHLOROFORM-d) d ppm 8.34 (s, 1 H), 8.24 (d, J= 8.07 Hz, 2 H), 7.80 (d, J= 8.31 Hz, 2 H), 6.91 (brs, 1 H), 6.59 (t, J = 6.60 Hz, 1 H), 4.61 (d, J= 5.87 Hz. 1 H). N-(l-(4-cyclopropyl-2-oxopyrimidin-l(2H)-yl)-2-oxo-2-(4-(trifluoromethyl)phenyl)ethyl) formamide

[0268] To a solution of N-( 1 -hydroxy-2-oxo-2-(4-(trifluoromethyl)phenyl)ethyl)formamide (15.0 g, 1.00 Eq, 60.7 mmol) in DCM (500 mL) was added PCIs (14.5 g, 1.15 Eq, 69.8 mmol) at 0 °C. The mixture was then allowed to warm to room temperature and stirred at temperature for 2 hours. The solvent was evaporated completely under vacuum. This crude material was triturated with hexanes and the solid collected by vacuum filtration. The resulting solid product A-(l-Atty. Docket: UCSF-849WOchloro-2-oxo-2-(4-(trifluoromethyl)phenyl)ethyl)formamide was dried under vacuum and used directly in the next step.

[0269] To a round bottom flask were added 4-cyclopropylpyrimidin-2( 1 H)-one (7.44 g, 0.90 Eq, 54.6 mmol), DMF (100 mL), and triethylamine (18.4 g, 25.4 mL, 3.00 Eq, 182 mmol). The mixture was then cooled to 0 °C and 2V-(l-chloro-2-oxo-2-(4-(trifluoromethyl)phenyl)ethyl)formamide (assuming 100% yield, 60.7 mmol) in DMF (50 mL) was added dropwise. The resulting reaction mixture was stirred at 25 °C for 2 hours. The reaction mixture was poured into ice water and extracted with EtOAc (2 x 500 mL). The combined organic layers were then washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to provide crude product. To this material was added ethyl acetate and the resulting solid was collected by filtration. The material was then washed with hexanes and dried under reduced pressure to yield -(l-(4-cyclopropyl-2-oxopyrirnidin- 1 (2H)-yl)-2-oxo-2-(4-(trifluoromethyl)phenyl)ethyl)formamide (7.50 g, 20.5 mmol, 33 %) as a solid. This material was used directly in the next step.

[0270] LCMS: (+ESI)[M+1]= 366.2.4-cyclopropyl-l-(5-(4-(trifluoromethyl)phenyl)oxawl-4-yl)pyrimidin-2(lH)-one

[0271] A-(l-(4-cyclopropyl-2-oxopyrimidin-l(2H)-yl)-2-oxo-2-(4-(trifhioromethyl)phenyl)ethyl) formamide (7.50 g, 1 Eq, 20.5 mmol) was combined with Eaton’s reagent (7.5% phosphorus(V) oxide in methanesulfonic acid, 73.3 g, 48.8 mL, 15.0 Eq, 308 mmol) and the mixture was heated to 70 °C for 150 minutes. The reaction was then poured into ice and basified with solid sodium bicarbonate. The aqueous mixture was then extracted with EtOAc (3 x 300 ml). The combined organic layers were washed with water and brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to give crude product. The crude material was purified by normal phase chromatography (40 g silica gel, 0-3% methanol in chloroform). The fractions containing product were evaporated under reduced pressure to yield 4-cyclopropyl-l-(5-(4-(trifluoromethyl)phenyl)oxazol-4-yl)pyrimidin-2( 1 H)-one (2.3 g, 6.5 mmol, 32 %) as a solid.

[0272] LCMS: (+ESI)[ M+1]- 348.1.Atty. Docket: UCSF-849WO

[0273] I H NMR (400 MHz, DMSO-d6) 5 ppm 8.67 ■■ 8.81 (m, I H). 8.05 ■■ 8.17 (m, 1 H). 7.84 - 7.93 (m, 2 H), 7.55 - 7.69 (m, 2 H). 6.60 - 6.72 (m, 1 H), 2.04 - 2.18 (m, 1 H), 1.08 - 1.22 (m, 4 H).4-cyclopropyl-l-{2-(l-methyl-2-oxo-6-auinolyl)-5-fD-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl}-2( IHj-pyrimidinone [Compound 227]

[0274] To a resealable vial were added 4-cyclopropyl-l-(5-(4-(trifluoromethyl)phenyl)oxazol-4-yl)pyrimidin-2(lH)-one (30 mg, 1 Eq, 86 pmol), 6-bromo-l-methylquinolin-2(lH)-one (31 mg, 1.5 Eq, 0.13 mmol), PdOAc2 (1.9 mg, 0.10 Eq, 8.6 pmol), dicyclohexyl(2',6'-diisopropoxy- [1,1'-biphenyl]-2-yl)phosphane (8.1 mg, 0.20 Eq, 17 pmol), K2CO3 (36 mg, 3 Eq, 0.26 mmol), and toluene (1 mL). The reaction was capped and heated at 115 °C for 16 hours. The crude reaction was mixed with 1 mL of DMF and directly purified by reverse phase chromatography (Cl 8 column, 10-100% MeCN in water with 0.1% TFA). This purification provided 4-cyclopropyLl-{2-(l-methyl-2-oxo-6-quinolyl)-5-[p-(trifhroromethyl)phenyl]-l,3-oxazol-4-yl}-2(lH)-pyrimidinone (8.5 mg, 17 pmol, 20 %) as a solid.

[0275] 1H NMR (400 MHz, CDC13) 88.39 - 8.27 (m, 2H), 7.90 (d. J = 9.3 Hz, 1H), 7.73 (dq, J = 14.8, 7.7 Hz, 5H), 7.60 (d, J = 8.8 Hz, 1H), 6.98 (d, J = 9.5 Hz, 1H), 6.51 (d, J = 6.9 Hz, 1H), 3.86 (s, 3H), 2.10 (dt, J = 8.1, 3.9 Hz, 1H), 1.51 - 1.43 (m, 2H), 1.35 (dt, J = 7.7, 3.5 Hz, 2H).

[0276] LCMS (M+H)+= 505.1. LCAP % at 280 nm = 97.9%.Compound 266: 4-cycloyroyyl-l-(2-(l-methyliso(iuinolin-6-yl)-5-(4- (trifluoromethyl}phenyl}oxazol-4-yl}pyrimidin-2(lH}-one4-cyclopropyl-l-[2-(l-methylisoquinolin-6-yl)-5-[4-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl]-l,2-dihydropyrimidin-2-one:

[0277] 6-Bromo-l -methylisoquinoline (1.77 g, 7.63 mmol, 1.5 eq), potassium carbonate (2.11 g, 15.3 mmol, 3.0 eq), pivalic acid (228 pl, 2.04 mmol, 0.4 eq), RuPhos (0.475 g, 1.02 mmol, 0.2Atty. Docket: UCSF-849WOeq), and 4-cyclopropyl- 1 - { 5-[4-(trifluoromethyl)phenyl]- 1,3-oxazol-4-yl }- 1,2-dihydropyrimidin-2-one (1.9 g, 5.09 mmol, 1.0 eq) were placed in a reaction tube with toluene (51.3 mL). After degassing with Ar for 10 minutes, palladium(II) acetate (0.114 g, 0.509 mmol, 0.1 eq) was added. The reaction vessel was sealed, and the reaction mixture was stirred at 115 °C for 16 hours. The crude reaction was concentrated under vacuum. The residue was treated with brine, and the mixture was extracted with dichloromethane (3 times). The organic layers were combined, dried over sodium sulfate, and concentrated under reduced pressure. The crude material was purified by normal phase chromatography (0-10% MeOH in DCM) to give 4-cyclopropyl-l-[2-(l-methylisoquinolin-6-yl)-5-[4-(trifluoromethyl)phenyl]-l,3-oxazol-4-yl]-l,2-dihydropyrimidin-2-one (1.5 g, 3.07 mmol, 60%).

[0278] LC-MS: 2.10 min, [M+H]+= 489.2, 99.04% @ 220 nm.

[0279] NMR (300 MHz. DMSO-< / 6) 58.82 (d, J= 1.7 Hz, 1H), 8.48 (d, J = 5.8 Hz, 1H), 8.45 - 8.38 (m, 1H), 8.32 (dd, J = 8.8. 1.8 Hz, 1H), 8.24 (d, J = 6.9 Hz. 1H). 7.97 - 7.86 (m, 3H), 7.86 - 7.77 (m, 2H), 6.74 (d, J= 6.9 Hz, 1H), 2.95 (s, 3H), 2.15 (qd, J= 6.8, 5.4 Hz, 1H), 1.27 - 1.11 (m, 4H).Synthesis of Compound 309. 4-c\cl()i)roi)\l-l-l5-(i)-fluoroi)hen\l)-2-( l-ine(hyl-6-isoiiuinol\'l)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone:N-( 2-(4-fluorophenyl )- 1 -hydroxy-2-oxoethyl jformamide

[0280] To a slurry of l-(4-fluorophenyl)-2,2-dihydroxyethan-l-one (10 g, 1.0 Eq, 59 mmol) in 1,4-dioxane (150 mL) was added formamide (5.3 g. 4.7 mL, 2 Eq, 0.12 mol) and the reaction mixture was heated at 90 °C for 16 hours. The reaction was concentrated and poured into water (300 mL). The resulting solid was filtered and rinsed with water (200 mL). The resulting solidAtty. Docket: UCSF-849WOmaterial was dried in a 50 °C vacuum oven for 24 hours. This material was A-(2-(4-fluorophcnyl )- 1 -hydroxy-2-oxocthy I (formamide (8.7 g, 75% yield, 80% purity).

[0281] NMR: (400 MHz, DMSO) 58.97 (d, J= 8.7 Hz, 1H), 8.15 - 8.03 (m, 3H), 7.38 (td, J = 8.7. 4.3 Hz, 2H). 6.77 (d, J = 7.1 Hz. 1H). 6.37 (t, J= 7.7 Hz, 1H).N-(l-(4-cyclopropyl-2-oxopyrimidm-l(2H)-yl)-2-(4-fluorophenyl)-2-oxoethyl)formamide

[0282] To a slurry of A-(2-(4-fhiorophenyl)-l-hydroxy-2-oxoethyl)formamide (300 mg, 1 Eq, 1.52 mmol) in DCM (5 mL) was added PCh (348 mg, 1.1 Eq, 1.67 mmol). The resulting homogeneous solution was stirred at 50 °C for 30 min. The mixture was cooled to room temperature, concentrated under reduced pressure, and dried in vacuo to give iV-(l-chloro-2-(4-fluorophenyl)-2-oxoethyl)formamide. This crude material was used directly and is unstable to storage. To a solution of A-(l-chloro-2-(4-fh.iorophenyl)-2-oxoethyl)formamide in DMF (3 mL) was added triethylamine (462 mg, 0.63 mL, 3 Eq, 4.56 mmol) followed by solid 4-cyclopropylpyrimidin-2(lH)-one (228 mg, 1.1 Eq, 1.67 mmol). The reaction mixture was stirred at ambient temperature for 30 minutes. The reaction was concentrated to dryness and water (15 mL) was added. A solid precipitated after the addition of water and it was collected and dried in a 50 °C vacuum oven for 16 hours. This gave A-(l-(4-cyclopropyl-2-oxopyrimidin-l(2H)-yl)-2-(4-fluorophenyl)-2-oxoethyl)formamide (242 mg, 768 pmol, 50.4 %). This material was used directly in the next reaction.4-cyclopropyl-l -( 5- 4-fluorophenyl)oxazol-4-yl)pyrimidin-2(l H)-one

[0283] A-(l-(4-Cyclopropyl-2-oxopyrimidin-l(2H)-yl)-2-(4-fluorophenyl)-2-oxoethyl)formamide (120 mg, 1 Eq, 381 pmol) was suspended in Eaton's reagent (7.5% phosphorus(V) oxide in methanesulfonic acid. 3 mL) and the resulting material was heated to 60 °C for 2 hours. The reaction was mixed with 1 mL of MeOH and directly purified by reverse phase chromatography (C18 HPLC column, 10- 100% MeCN in water with 0.1% TFA). This purification provided 4-cyclopropyl- l-(5-(4-fluorophenyl)oxazol-4-yl)pyrimidin-2( lH)-one (60 mg, 0.20 mmol, 53 %).

[0284] NMR: (400 MHz, CDC13) 58.00 (s, 1H), 7.87 (d, J = 7.0 Hz, 1H), 7.56 - 7.42 (m, 2H), 7.20-7.08 (m, 2H), 6.42 (d, 7= 7.1 Hz, 1H), 2.21 (ddd,. / = 7.7, 4.9, 2.9 Hz, 1H), 1.46 (ddd, J= 12.6. 6.1, 3.4 Hz, 4H).Atty. Docket: UCSF-849WO4-cyclopropyl-l-f 5-(p-fluorophenyl)-2-( l-methyl-6-isoquinolyl)-l,3-oxazol-4-yl]-2( 1 H)-pyrimidinone f Compound 309]

[0285] To a resealable vial were added 4-cyclopropyl-l-(5-(4-fluorophenyl)oxazol-4-yl)pyrimidin-2(lH)-one (30 mg, 1 Eq, 0.10 mmol), 6-bromo-l -methylisoquinoline (34 mg, 1.5 Eq, 0.15 mmol), pivalic acid (4.1 mg, 0.40 Eq, 40 pmol). Pd(OAc)2 (2.3 mg, 0.10 Eq, 10 pmol), dicyclohexyl(2',6'-diisopropoxy-[l, T-biphenyl]-2-yl)phosphane (9.4 mg, 0.20 Eq, 20 pmol), and K2CO3 (42 mg, 3 Eq, 0.30 mmol). Toluene (1 mL) was then added, and the sealed vessel was heated at 115 °C for 16 hours. The crude reaction was cooled to room temperature and mixed with 1 mL of DMF. The mixture was then syringe filtered and directly purified by reverse phase chromatography (Cl 8 HPLC column, 10-100% MeCN in water with 0.1% TFA). This purification provided 4-cyclopropyl-l-[5-(p-fhiorophenyl)-2-(l-methyl-6-isoquinolyl)-l,3-oxazol-4-yl]-2(lH)-pyrimidinone (18 mg, 41 pmol, 41 %).

[0286] NMR: (400 MHz, MeOD) 58.89 (s, 1H), 8.64 (q, J = 8.9 Hz, 2H), 8.44 (d, J - 6.5 Hz, 1H), 8.32 (d, J = 6.6 Hz, 1H), 7.90 (d, J = 6.9 Hz, 1H), 7.79 - 7.60 (m, 2H), 7.23 (t, J = 8.5 Hz, 2H), 6.65 (d, J = 7.0 Hz, 1H), 3.27 (s, 3H), 2.16 - 2.04 (m, 1H), 1.45 - 1.23 (m, 4H).

[0287] LCMS (ESI+): m / z 439.1 [M+H]+

[0288] HPLC: RT: 1.92 minCompound 503: 4-cyclopropyl-l-(5-(4-fluorophenyl)-2-(2-methylbenzofd]oxazol-6-yl)oxazol-4-yl)pyrimidin-2(lH)-oneN=\O N\= / O / =N Pd(PPh3)4, Cs2CO3c> > rr oo \=J bromo(1,10-phenanthroline)- (triphenylphosphine)copper(l) N \ / / Br4-cyclopropyl-l-(5-(4-fluorophenyl)-2-(2-methylbenzo[d]oxazol-6-yl)oxazol-4-yl)pyrimidin-2(lH)-one:

[0289] To a resealable vial were added 4-cyclopropyl-l-(5-(4-fluorophenyl)oxazol-4-yl)pyrimidin-2(lH)-one (0.050 g, 1 Eq, 0.17 mmol), 6-bromo-2-methy 1 benzo[ ^oxazole (46 mg, 1.3 Eq, 0.22 mmol), CuBr(phenan)(PPh3) (9.9 mg, 0.1 Eq, 17 pmol), Pd(PPh3)4 (19 mg, 0.1 Eq,Atty. Docket: UCSF-849WO17 prnol), CS2CO3 (0.12 g, 2.2 Eq, 0.37 mmol), and toluene (3.0 mL). The vial was capped, purged with nitrogen for 5 minutes, and heated at 105 °C for 16 hours. The crude mixture was concentrated onto Celite and purified with normal phase column chromatography (24 g silica gel column, 0-5% MeOH / DCM) to afford crude product. This material was triturated in MeOH, and the resulting solid was collected and dried to afford 4-cyclopropyl-l-(5-(4-fluorophenyl)-2-(2- methylbenzo[d]oxazol-6-yl)oxazol-4-yl)pyrimidin-2(1H)-one (10.4 mg, 24.4 pmol, 14 %) as a solid.

[0290] LCMS (M+H)+= 429.1. LCAP % at 280 nm 95%.

[0291] NMR (400 MHz, MeOD) δ 8.36 (d, J= 1.5 Hz, 1H), 8.18 (dd, J = 8.4, 1.6 Hz, 1H), 8.08 (d, J = 6.9 Hz, 1H), 7.81 (d, J = 8.4 Hz, 1H), 7.70 – 7.61 (m, 2H), 7.27 (t, J = 8.8 Hz, 2H).6.73 (d, J = 6.9 Hz, 1H), 2.72 (s, 3H), 2.21 - 2.10 (m, 1H), 1.39- 1.25 (m, 4H).Compound 504: 4-c\'cl()i)roi)\'l-i-(5-(4-fluoroi)lien\'l)-2-( l-metli\l-lH-i)\'ra-,olol3,4-cli)xridin- 5-\l)oxa-,ol-4-\4)u\riinidin-2( 1 II)-onePd(OAc)2, RuPhos, K2CO3bromo(1, 10-phenanthroline)- (triphenylphosphine)copper(l)4-cyclopropyl-l-[5-(4-fluorophenyl)-2-{l-methyl-lH-pyrazolo[3,4-c]pyridin-5-yl}-l,3- oxazol-4-yl]-l,2-dihydropyrimidin-2-one:

[0292] Under inert atmosphere, 4-cyclopropyl-l-[5-(4-fluorophenyl)-l,3-oxazol-4-yl]-l,2- dihydropyrimidin-2-one (0.56 g, 1.71 mmol, 1.0 eq), potassium carbonate (0.711 g, 5.14 mmol, 3.0 eq), bromo(l,10-phenanthroline)(triphenylphosphine)copper(I) (0.151 g, 0.257 mmol, 0.15 eq), RuPhos (0.16 g. 0.343 mmol, 0.2 eq), and 5-bromo-1-methyl-1H-pyrazolo[3,4-c]pyridine (0.545 g, 2.57 mmol, 1.5 eq) were suspended in dioxane (11.2 mL). The resulting mixture was purged with Ar for 5 minutes prior to the addition of palladium(II) acetate (0.058 g, 0.257 mmol, 0.15 eq). The reaction vial was sealed, and the reaction mixture was stirred at 120 °C for 4 hours. After cooling to room temperature, the reaction mixture was diluted with dichloromethane andAtty. Docket: UCSF-849WOfiltered through a pad of celite. The celite pad was washed with a mixture of dichloromethane and methanol (9 / 1, v / v). The filtrate was concentrated under reduced pressure to give the crude product which was purified via normal phase column chromatography (0-5% MeOH in DCM) to provide 4-cyclopropyl- l-[5-(4-fluorophenyl)-2-{ 1 -methyl- 1 H-pyrazolo[ 3,4-c ] pyridi n-5-y 1 } - 1,3-oxazol-4-yl]-l,2-dihydropyrimidin-2-one (0.308 g, 0.72 mmol, 42%) as a solid.

[0293] LC-MS: 2.50 min, [M+H]+= 429.2, 98.4% @ 205 nm

[0294] ’H NMR (300 MHz. DMSO-tfc) δ 9.36 (t, J = 1.1 Hz, 1H), 8.65 (d, J= 1.3 Hz, 1H), 8.38 (d, J= 0.8 Hz, 1H), 8.21 (d, J= 6.9 Hz, 1H), 7.60 (dd, J= 8.8, 5.3 Hz, 2H), 7.41 (t, J= 8.9 Hz, 2H), 6.70 (d, J= 6.9 Hz, 1H), 4.27 (s, 3H), 2.20 – 2.07 (m, 1H), 1.24 – 1.12 (m, 4H).Compound 505: _ 6-(4-(4-cyclopropyl-2-oxopyrimidin-l(2H)-yl)-5-(4-fluorophenyl)oxazol- 2- l)-2-methylisoindolin-l-onePd(OAc)2, RuPhos, K2CO3bromo(1, 10-phenanthroline)- (triphenylphosphine)copper(l)6-[4-(4-cyclopropyl-2-oxo-l,2-dihydropyrimidin-l-yl)-5-(4-fluorophenyl)-l,3-oxazol-2-yl]-2-methyl-2,3-dihydro-lH-isoindol-l-one:

[0295] Under inert atmosphere, 4-cyclopropyl-l-[5-(4-fluorophenyl)-l,3-oxazol-4-yl]-l,2-dihydropyrimidin-2-one (0.105 g, 0.336 mmol, 1.0 eq), potassium carbonate (0.139 g, 1.01 mmol, 3.0 eq), bromo(l,10-phenanthroline)(triphenylphosphine)copper(I) (0.03 g, 0.05 mmol, 0.15 eq), RuPhos (0.031 g, 0.067 mmol, 0.2 eq), and 6-bromo-2-methylisoindolin-l-one (0.099 g, 0.437 mmol, 1.3 eq) were suspended in dioxane (2.0 mL). The resulting mixture was purged with Ar for 5 minutes prior to the addition of palladium(II) acetate (0.011 g, 0.05 mmol, 0.15 eq). The reaction vial was sealed, and the reaction mixture was stirred for 1.5 hours at 120 °C. After cooling to room temperature, the reaction mixture was diluted with dichloromethane and filtered through a pad of celite. The celite pad was washed with a mixture of dichloromethane and methanol (9 / 1, v / v). The filtrate was concentrated under reduced pressure to give the crudeAtty. Docket: UCSF-849WOproduct. The crude product was purified via normal phase column chromatography (0-4% MeOH in DCM). Fractions containing the desired product were concentrated under reduced pressure. The residue was triturated with methanol, collected by filtration, washed with methanol, and dried under vacuum to provide 6-[4-(4-cyclopropyl-2-oxo-l,2-dihydropyrimidin-l-yl)-5-(4-fluorophenyl)- l,3-oxazol-2-yl]-2-methyl-2,3-dihydro-lH-isoindol- 1-one (0.025 g, 0.056 mmol, 17%).

[0296] LC-MS: 2.53 min, [M+HJ+= 443.2, 98.4% @ 210 nm.

[0297] rH NMR (300 MHz, DMSO-t / 6) δ 8.45 – 8.28 (m, 2H), 8.19 (d, J = 6.9 Hz, 1H), 7.96 – 7.74 (m, 1H), 7.76 – 7.55 (m, 2H), 7.48 – 7.19 (m, 2H), 6.70 (d, J = 6.9 Hz, 1H), 4.59 (s, 2H), 3.12 (s, 3H), 2.17 – 1.93 (m, 1H), 1.41 – 0.92 (m, 4H).Compound 506: 4-cyclopropyl-1-(2-(4-(difluoromethyl)phenyl)-5-(4-fluorophenyl)oxazol-4-yl)pyrimidin-2(1H)-onePd(PPh3)4, K2CO3bromo(1, 10-phenanthroline)- (triphenylphosphine)copper(l)4-cyclopropyl-1-(2-(4-(difluoromethyl)phenyl)-5-(4-fluorophenyl)oxazol-4-yl)pyrimidin-2(1H)-one:

[0298] To a 25 mL sealable tube were added 4-cyclopropyl-1-(5-(4-fluorophenyl)oxazol-4-yl)pyrimidin-2(1H)-one (100 mg, 336 umol. 1 Eq.), l-bromo-4-(difluoromethyl)benzene (104 mg, 505 pmol, 1.5 Eq.), and toluene (5 mL). The mixture was purged with argon for 10 minutes. Then, potassium carbonate (139 mg, 1.01 mmol, 3 Eq.), bromo(l,10-phenanthroline)(triphenylphosphine)copper (20 mg, 34 pmol, 0.1 Eq.), and Pd(PPh3)4(39 mg, 37 pmol, 0.1 Eq.) were added while purging with argon. Then, the tube was sealed and heated to 110 °C for 16 hours. The reaction mixture was cooled to ambient temperature, diluted with 5% methanol in DCM, and filtered. The filtrate was evaporated under reduced pressure. The resulting crude compound was purified by flash normal phase chromatography (12 g column,Atty. Docket: UCSF-849WOsilica gel, 70-90% EtOAc in hexanes) to yield 4-cyclopropyl-l-(2-(4-(difluoromethyl)phenyl)-5-(4-fluorophenyl)oxazol-4-yl)pyrimidin-2( 1 H)-one (90 mg, 208 pmol, 62%) as a solid.

[0299] LCMS: (+ESI)[M+H]+= 424.3.

[0300] NMR (400 MHz, DMSO-de) 8 = 8.27 (br d, 7 = 8.2 Hz, 2H), 8.17 (d, 7= 6.8 Hz, 1H), 7.80 (br d, 7 = 8.0 Hz, 2H), 7.63 (dd, 7 = 5.3, 8.9 Hz, 2H), 7.40 (br t, 7 = 8.8 Hz, 2H), 7.16 (t, 7 = 55.6 Hz, 1H), 6.69 (d, 7 = 7.0 Hz, 1H), 2.18 - 2.06 (m, 1H), 1.21 - 1.14 (m, 4H).Compound 507: 4-cyclopropyl-l-(5-(4-fluorophenyl)-2-(l-methyl-lH-indazol-5-yl)oxazol-4-yl)pyrimidin-2( lH)-onePd(PPh3)4, K2CO3bromo(1, 10-phenanthroline)- (triphenylphosphine)copper(l)4-cyclopropyl-1-(5-(4-fluorophenyl)-2-(1-methyl-1H-indazol-6-yl)oxazol-4-yl)pyrimidin-2(1H)-one:

[0301] To a 25 mL sealable tube were added 4-cyclopropyl-1-(5-(4-fluorophenyl)oxazol-4-yl)pyrimidin-2(1H)-one (58.5 mg, 197 pmol, 1 Eq.), 6-bromo- 1 -methyl- IH-indazole (62.3 mg, 295 pmol, 1.5 Eq.), and toluene (2 mL). The mixture was degassed with argon for 10 minutes. Then, potassium carbonate (109 mg, 787 pmol, 4 Eq.), Pd(PPh3)4(23 mg, 20 pmol, 0.1 Eq.), and bromo(l,10-phenanthroline)(triphenylphosphine)- copper (17 mg, 29 pmol, 0.15 Eq.) were added while purging with argon. The tube was sealed, and the resulting reaction mixture was heated to 110 °C for 16 hours. The reaction mixture was cooled to ambient temperature, diluted with DCM, and filtered. The filtrate was evaporated under reduced pressure to afford crude compound. The crude compound was purified by flash normal phase chromatography (12 g column, silica gel, 0-100% EtOAc in hexanes). The fractions containing product were combined and concentrated under vacuum. The resulting compound was triturated with ethyl acetate, collected by vacuum filtration, and dried to afford 4-cyclopropyl-1-(5-(4-fluorophenyl)-2-(1-methyl-1H-indazol-6-yl)oxazol-4-yl)pyrimidin-2(1H)-one (55 mg, 124 pmol, 63%) as a solid.Atty. Docket: UCSF-849WO

[0302] (+ESI) [M+H]+= 428.0.

[0303] NMR (400 MHz, DMSO-d6) 5 = 8.62 (s, 1H), 8.26 (s, 1H), 8.20 (d, J = 6.8 Hz, 1H), 8.14 - 8.08 (m, 1H), 7.86 (d, J = 8.8 Hz, 1H), 7.62 (dd, J = 5.3, 8.7 Hz, 2H), 7.40 (br t. J = 8.9 Hz, 2H), 6.69 (d. J= 6.8 Hz, 1H), 4.12 (s, 3H), 2.17 - 2.07 (m. 1H). 1.21 - 1.14 (m, 4H).Compound 508: 4-c\'cloi)roi)\l-l-(5-(4-fluoroi)hen\'h-2-( l-ineth\'l-lH-i)\rrolol2,3-ch)\ridin-5- \l)oxg-ol-4-\l)p\rimidin-2(! II )-oneCui, K2CO3, pivalic acid B is-( 1 -adamantyl)-butyl- phosphane, cataCXium pd G34-cyclopropyl-1-(5-(4-fluorophenyl)-2-(1-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)oxazol-4-yl)pyrimidin-2(1H)-one:

[0304] To a 30 mL sealable tube were added 4-cyclopropyl-1-(5-(4-fluorophenyl)oxazol-4-yl)pyrimidin-2(1H)-one (100 mg, 336 pmol, 1 Eq.), 5-bromo-1-methyl-1H-pyrrolo[2,3-c]pyridine (106 mg, 505 pmol, 1.5 Eq.), potassium carbonate (232 mg, 1.68 mmol, 5 Eq.), and toluene (5.0 mL). The reaction mixture was then degassed with argon for 10 minutes. Then, di((3S,5S,7S)-adamantan-1-yl)(butyl)phosphane (18 mg, 50 pmol. 0.15 Eq.), cataCXium Pd G3 (36 mg, 50pmol, 0.15 Eq.), copper(I) iodide (13 mg, 67 pmol, 0.2 Eq.), and pivalic acid (17 mg, 17 pmol, 0.05 Eq.) were added while purging with argon. The tube was sealed and heated to 110 °C for 16 hours. The reaction mixture was cooled to ambient temperature, diluted with DCM (50 mL), and filtered through a pad of Celite. The Celite cake was washed with DCM. The combined filtrate was concentrated under reduced pressure. The crude compound was purified by flash normal phase chromatography (12 g column, 0-10% MeOH in EtOAc). The fractions containing product were evaporated under reduced pressure and the obtained compound was triturated with ethyl acetate. The slurry was filtered and the solid dried under vacuum to afford 4-cyclopropyl-1-(5-(4-fluorophenyl)-2-(1-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)oxazol-4-yl)pyrimidin-2(1H)-one (90 mg, 0.20 mmol, 61 %) as a solid.Atty. Docket: UCSF-849WO

[0305] (+ESI)[M+H]+= 428.3.

[0306] NMR (400 MHz, DMSO-d6) 5 = 9.01 (s, 1H), 8.44 (d, J = 0.9 Hz, 1H), 8.21 (d, J= 6.8 Hz, 1H), 7.72 (d, J = 3.0 Hz, 1H), 7.58 (dd, J = 5.3, 8.9 Hz, 2H), 7.40 (t, J = 8.9 Hz, 2H), 6.70 -6.68 (m, 2H), 4.00 (s, 3H), 2.18 - 2.09 (m. 1H), 1.17- 1.15 (m. J = 3.3 Hz, 4H).Compound 509: 4-c\'cloprop\4-I-(5-(4-fluoroplieii\'h-2-(l-(p\ridin-3-\l)-l II-p\ra:,ol-3-\l)oxg-ol-4-\l)p\rimidin-2(! II )-onePd(OAc)2, RuPhos, K2CO34-cyclopropyl-l-(5-(4-fluorophenyl)-2-(l-(pyridin-3-yl)-177-pyrazol-3-yl)oxazol-4-yl)pyrimidin-2(l / / )-one

[0307] To a 25 mL sealable tube were added 4-cyclopropyl-l-(5-(4-fluorophenyl)-oxazol-4-yl)pyrimidin-2(lH)-one (100 mg, 336 pmol, 1 Eq.), toluene (4.0 mL), 3-(3-bromo-lH-pyrazol-l-yl)pyridine (90.4 mg, 404 pmol, 1.2 Eq.), and potassium carbonate (139 mg, 1.01 mmol, 3 Eq.). The mixture was degassed with argon for 5 minutes. Then, dicyclohexylphosphino-2',6'-diisopropoxybiphenyl (15.7 mg, 33.6 pmol, 0.1 Eq.) and palladium acetate (7.5 mg, 33 pmol, 0.1 Eq.) were added under continuing argon purging which was then continued for 5 minutes. The tube was sealed, and the resulting reaction mixture was heated to 105 °C for 16 hours. The reaction mixture was cooled and filtered through Celite. The filtrate was washed with DCM (20 mL). The filtrate was concentrated under vacuum and the crude compound was purified by flash normal phase chromatography (12 g column, 50-100% EtOAc in hexanes). The compound obtained was then triturated with ethyl acetate. This material was then further purified preparative HPLC (Cl 8 column, 10-100% MeCN in water with 0.1% TFA) to afford 4-cyclopropyl-1-(5-(4-fluorophenyl)-2-(1-(pyridin-3-yl)-1H-pyrazol-3-yl)oxazol-4-yl)pyrimidin-2(1H)-one (9.5 mg, 21.5 pmol, 6.4%) as a solid.

[0308] LCMS: (+ESI)[M+H]+= 441.2Atty. Docket: UCSF-849WO

[0309] ’H NMR (400 MHz, DMSO-d6) 5 = 9.23 (d, J= 2.5 Hz, 1H), 8.87 (d, J = 2.6 Hz, 1H), 8.63 (dd, J = 1.2, 4.7 Hz, 1H), 8.40 - 8.35 (m, 1H), 8.18 (d, J= 6.8 Hz, 1H), 7.64 (dd, J = 4.6, 8.3 Hz, 1H), 7.61 - 7.55 (m. 2H), 7.45 - 7.37 (m, 2H), 7.29 (d, J= 2.6 Hz, 1H). 6.69 (d, J = 7.0 Hz.1H), 2.16 - 2.08 (m, 1H), 1.21 - 1.14 (m, 4H).Compound 510: 4-c\'cl()i)roi)\'l-l-(5-(4-fluoroi)hen\'l)-2-( l-meth\l-l H-iiida-.ol-6-\l)oxa-ol-4-yl)pyrimidin-2( lH)-onePd(PPh3)4, K2CO3bromo(1,10-phenanthroline)- (triphenylphosphine)copper(l)4-cyclopropyl-l-(5-(4-fluorophenyl)-2-(l-methyl-lH-indazol-6-yl)oxazol-4-yl)pyrimidin-2(lH)-one:

[0310] To a 25 mL sealable tube were added 4-cyclopropyl-l-(5-(4-fluorophenyl)oxazol-4-yl)pyrimidin-2(lH)-one (100 mg, 336 pmol, 1 Eq.), 6-bromo-1-methyl-1H-indazole...

Claims

Atty. Docket: UCSF-849WOCLAIMS:

1. A method of measuring protein aggregates in a patient by a technique, comprising:a) administering a first compound and a second compound to the patient, wherein the first compound is not detectable by the technique, and wherein the second compound is detectable by the technique;b) allowing the first compound and the second compound to bind the protein aggregates; and c) detecting the binding of the second compound to the protein aggregatesthereby measuring the protein aggregates in the patient.

2. The method of claim 1, wherein the first compound is administered prior to, coincident with, and / or after, the administration of the second compound.

3. The method of claim 1, wherein the ratio of first compound to second compound administered to the patient is from 3:1 to 30,000:1.

4. The method of claim 1, wherein the first compound and the second compound otherwise have the same chemical structure.

5. The method of claim 1, wherein the first compound and the second compound have different chemical structures.

6. The method of claim 1, wherein the second compound comprises at least one radiolabeled atom and the first compound does not comprise a radiolabeled atom.

7. The method of claim 6, wherein the at least one radiolabeled atom is [2H], [3H], [11C], [18F], [13N], or a combination thereof when there is more than one radiolabeled atom.

8. The method of claim 1, wherein the technique is positron emission tomography (PET).

9. The method of claim 1, wherein the protein aggregates are in the brain of the patient.

10. The method of claim 1, wherein the protein aggregates are tau aggregates, alpha-synuclein aggregates, amyloid aggregates, or a combination thereof.Atty. Docket: UCSF-849WO11. The method of claim 1 for diagnosing and monitoring the treatment of a tauopathy, an alpha-synucleinopathy, or an amyloidopathy.

12. The method of claim 1 for diagnosing and / or monitoring the treatment of spongiform encephalopathies (such as Creutzfeldt-Jakob disease (CJD)), multiple system atrophy (MSA), Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis (ALS), Amyotrophic lateral sclerosis / Parkinsonism-dementia complex, anti-IgLON5-related tauopathy, Caribbean Parkinsonism, Chronic traumatic encephalopathy. Dementia with Lewy Bodies (DLB), Diffuse neurofibrillary tangles with calcification, Down syndrome, Familial British dementia, Familial Danish dementia, Niemann-Pick disease-type C, Non-Guamanian motor neuron disease with neurofibrillary tangles, Postencephalitic Parkinsonism, Primary age-related tauopathy.Progressive ataxia and palatal tremor, Tangle-only dementia, Familial frontotemporal dementia and Parkinsonism, Pick's disease, Argyrophilic grain disease, Corticobasal degeneration, Guadeloupean Parkinsonism, Globular glial tauopathy. Huntington's disease. Progressive supranuclear palsy, SLC9a-related Parkinsonism, or Tau astrogliopathy.

13. A method of measuring the clinical efficacy of a therapeutic agent for a disease associated with protein aggregates in a patient, comprising:a) before treatment with said therapeutic agent, administering a first compound to the patient. wherein the first compound binds to the protein aggregates and is not detectable by the technique, and administering a second compound to the patient, wherein the second compound binds to the protein aggregates and is detectable by the technique, wherein the first compound is administered prior to, and / or coincident with, the second compound; b) measuring the amount of protein aggregates in the patient's brain tissue before treatment; c) after treatment with said therapeutic agent, administering a first compound to the patient. wherein the first compound binds to the protein aggregates and is not detectable by the technique, and administering a second compound to the patient, wherein the second compound binds to the protein aggregates and is detectable by the technique, wherein the first compound is administered prior to, and / or coincident with, the second compound;Atty. Docket: UCSF-849WOd) measuring the amount of protein aggregates in the patient's brain tissue after treatment; and e) analyzing whether said therapeutic agent maintained or reduced the amount of protein aggregates in the patientthereby measuring the clinical efficacy of the therapeutic agent.

14. A diagnostic composition for measuring protein aggregates, comprising:a) a radiolabeled compound;b) a non-radiolabeled compound; andc) a pharmaceutically acceptable excipientwherein the radiolabeled compound and the non-radiolabeled compound bind to the protein aggregates.

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