Heteroaryl topoisomerase inhibitors and uses thereof

Abstract

The present disclosure provides compounds of Formula (I-A) or Formula (I-B) useful as topoisomerase inhibitors and pharmaceutical compositions comprising the same. Methods of making and using the disclosed compounds are also provided.

Description

[0001] Attorney Docket No.103361-644WO1 HETEROARYL TOPOISOMERASE INHIBITORS AND USES THEREOF CROSS-REFERENCE TO RELATED APPLICATIONS This application claims the benefit of priority to United States Provisional Application No. 63 / 552,351 filed February 12, 2024, the disclosure of which is incorporated herein by reference in its entirety. STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT This invention was made with government support under grant / contract numbers R21 AI148986 and R01 AI173072 awarded by the National Institutes of Health. The government has certain rights in the invention. BACKGROUND It has been estimated that 10 million people per year will die from drug-resistant infections by the year 2050 (Jones, J. A., et al. Med. Chem. Commun.2016, DOI:10.1039 / C6MD00232C). Thus, infections caused by multidrug-resistant pathogens such as methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa present a critical threat to human health. Surveillance of antibacterial susceptibility among clinical isolates continues to reveal new mechanisms of resistance, including to antibiotics traditionally considered the last lines of defense, such as carbapenems (Morrill, H. J., et al. Open For. Infect. Dis. 2015, 2, ofv050) and even colistin (Liu, Y-Y., et al. Lancet Infect. Dis.2016, 16, 161; Schwarz, S., et al. J. Antimicrob. Chemother.2016, 71, 2066). Despite tremendous advances in genetics and high-throughput screening, the development of antibiotics against novel biological targets has proven exceptionally difficult. The advancement of next-generation inhibitors from established classes of antibiotics such as fluoroquinolones likewise presents difficulties, e.g., preexisting resistance and clinical efficacy / safety differentiation. In light of these and other challenges, antibacterial research in the pharmaceutical industry, long a source of new medicines, has dwindled substantially. Advances in other areas of medicine, including cancer therapy, surgery, and organ transplantation, critically require the availability of effective antibiotics. The confluence of Attorney Docket No.103361-644WO1 diminished private investment and rising resistance to life-saving medications thus presents an extraordinary threat to individual patients and to modern medicine. In order to avoid a post- antibiotic era (Alanis, A. J. Arch. Med. Res. 2005, 36, 697), new antibacterial therapies and new approaches to preventing, diagnosing, and treating infections are desperately needed. Bacteria are historically grouped into two categories based on their cellular structure, and this distinction helps to guide the diagnosis and treatment of bacterial infections. Gram-positive bacteria possess a comparatively thick peptidoglycan cell wall, and Gram-negative bacteria possess a thinner peptidoglycan layer further surrounded by an outer membrane. Both categories give rise to life-threatening infections, and both have been associated with the emergence of multidrug resistance. Enterococcus faecium and Methicillin-Resistant Staphylococcus aureus (MRSA) represent important examples of Gram-positive pathogens. The Centers for Disease Control (CDC) estimates that MRSA alone causes >11,000 fatalities per year in the United States. Gram-negative pathogens include Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and various Enterobacter species, among many others. Together, these six types of Gram-positive and Gram-negative bacteria, known by the acronym ESKAPE pathogens, comprise some of the most significant causes of multidrug-resistant (MDR) infections today. Effective antibacterial therapy typically abrogates a process that bacteria require to survive (an “essential” target). Such processes include the synthesis and maintenance of proteins, DNA, and the bacterial cell wall (Kohanski, M. A., et al. Nature Rev. Microbiol.2010, 8, 423). These targets are largely intracellular, meaning that most antibiotics need to penetrate the bacterial cell in order to exert their effect. The outer membrane of Gram-negative bacteria constitutes a particularly significant barrier to cell entry, and scientists currently lack a sufficient understanding of the molecular features that govern Gram-negative cell penetration (vide infra) (Scorciapino, M. A., et al. Future Med. Chem. 2016, 8, 1047). This fact, coupled with the robust set of resistance mechanisms employed by Gram-negative microorganisms (Ruppe, E., et al. Ann. Intensive Care 2015, 5, 21), renders the cure of infections caused by these bacteria particularly challenging. DNA replication is essential for the survival of bacteria, and the heterotetrameric (A2B2) bacterial type II topoisomerases DNA gyrase and Topoisomerase IV (TopoIV) are important to this process (Mayer, C., et al. Chem. Rev.2014, 114, 2313; Collin, F., et al. Appl. Microbiol. Biotechnol.2011, 92, 479; Bisacchi, G. S., et al. Annual Rep. Med. Chem.2009, 44, 379; Black, M. T., et al. Curr. Opin. Invest. Drugs 2009, 10, 804; Bradbury, B. J., et al. Curr. Opin. Pharmacol.2008, 8, 574; Mitscher, L. A. Chem. Rev.2005, 105, 559; Hooper, D. C. Clin. Inf. Attorney Docket No.103361-644WO1 Dis. 2000, 31 (Suppl. 2), S24). The widely used fluoroquinolone (FQ) class of antibiotics targets this mechanism. The commercially successful and medically important FQ class of antibacterial agents exemplifies the enormous potential of disrupting these targets and reveals the possibility of achieving both Gram-positive and Gram-negative spectra (Bax, B. D., et al. Nature 2010, 466, 935). However, FQ resistance has emerged via a number of mechanisms (Blumberg, H. M., et al. J. Inf. Dis.1991, 163, 1279; Hooper, D. C. Emerging Inf. Dis.2001, 7, 337; Jacoby, G. A. Clin. Infect. Dis.2005, 41 (Suppl.2), S120). The history of the FQs has also informed more recent drug discovery strategies, notably a focus on the minimization of hERG inhibition (a cardiotoxicity liability) and the design of dual-targeting (gyrase and TopoIV) inhibitors to slow clinical resistance emergence (Id.; Blumberg, H. M., et al. J. Inf. Dis.1991, 163, 1279; Wohlkonig, A.; Chan, P. F., et al. Nat. Struct. Mol. Biol.2010, 17, 1152; Aldred, K. J., et al. Biochem. 2014, 53, 1565; Onodera, Y., et al. J. Antimicrob. Chemother. 1999, 44, 533; Cheng, J., et al. Antimicrob. Agents Chemother.2007, 51, 2445; Morrow, B. J., et al. Antimicrob. Agents Chemother.2011, 55, 5512). Given exhaustive efforts directed toward FQs over several decades, as well as multiple mechanisms of resistance in the clinic (Hooper, D. C. Emerging Inf. Dis. 2001, 7, 337; Jacoby, G. A. Clin. Infect. Dis. 2005, 41 (Suppl. 2), S120), the design and synthesis of type II topoisomerase inhibitors with non-FQ chemotypes presents a compelling need. The compositions and methods disclosed herein address these and other needs. SUMMARY In accordance with the purposes of the disclosed materials and methods, as embodied and broadly described herein, the disclosed subject matter, in one aspect, relates to compounds, compositions, and methods of making and using compounds and compositions. In one aspect, a compound is provided of Formula I-A or Formula I-B: Attorney Docket No.103361-644WO1 or a pharmaceutically acceptable salt thereof, wherein all variables are as defined herein. In another aspect, a pharmaceutical composition is provided comprising a compound described herein, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. In yet another aspect, a method is provided of treating an infection in a subject in need thereof comprising administering a compound described herein or a pharmaceutically acceptable salt thereof. The details of one or more aspects of the disclosure are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the disclosure will be apparent from the description, the drawings, and the claims. DETAILED DESCRIPTION The following description of the disclosure is provided as an enabling teaching of the disclosure in its best, currently known aspects. Many modifications and other aspects disclosed herein will come to mind to one skilled in the art to which the disclosed compositions and methods pertain, benefiting from the teachings presented in the descriptions herein and the associated drawings. Therefore, it is understood that the disclosures are not limited to the specific aspects disclosed and that modifications and other aspects are intended to be included within the scope of the appended claims. The skilled artisan will recognize many variants and adaptations of the aspects described herein. These variants and adaptations are intended to be included in the teachings of this disclosure and to be encompassed by the claims herein. Although specific terms are employed herein, they are used in a generic and descriptive sense only and not for purposes of limitation. As apparent to those of skill in the art upon reading this disclosure, each of the individual aspects described and illustrated herein has discrete components and features that may be Attorney Docket No.103361-644WO1 readily separated from or combined with the features of any of the other several aspects without departing from the scope or spirit of the present disclosure. Any recited method can be carried out in the order of events recited or any other order that is logically possible. Unless otherwise expressly stated, it is in no way intended that any method or aspect set forth herein be construed as requiring that its steps be performed in a specific order. Accordingly, where a method claim does not explicitly state in the claims or descriptions that the steps are to be limited to a particular order, it is in no way intended that an order be inferred in any respect. This holds for any possible non-express basis for interpretation, including logic concerning the arrangement of steps or operational flow, meaning derived from grammatical organization or punctuation, or the number or type of aspects described in the specification. All publications mentioned herein are incorporated by reference to disclose and describe the methods or materials in connection with which the publications are cited. The publications discussed herein are provided solely for their disclosure before the filing date of the present application. Further, the dates of publication provided herein can be different from the actual publication dates, which can require independent confirmation. It is also to be understood that the terminology herein describes particular aspects only and is not intended to be limiting. Unless defined otherwise, all technical and scientific terms herein have the same meaning as commonly understood by one of ordinary skill in the art to which the disclosed compositions and methods belong. It can be further understood that terms, such as those defined in commonly used dictionaries, should be interpreted as having a meaning that is consistent with their meaning in the context of the specification and relevant art and should not be interpreted in an idealized or overly formal sense unless expressly defined herein. Before describing the various aspects of the present disclosure, the following definitions are provided and should be used unless otherwise indicated. Additional terms may be defined elsewhere in the present disclosure. Definitions As used herein, “comprising” is interpreted as specifying the presence of the stated features, integers, steps, or components but does not preclude the presence or addition of one or more features, integers, steps, components, or groups thereof. Moreover, each of the terms “by,” “comprising,” “comprises,” “comprised of,” “including,” “includes,” “included,” “involving,” Attorney Docket No.103361-644WO1 “involves,” “involved,” and “such as” are used in their open, non-limiting sense and may be used interchangeably. Further, the term “comprising” is intended to include examples and aspects encompassed by the terms “consisting essentially of” and “consisting of.” Similarly, “consisting essentially of” is intended to include examples encompassed by the term “consisting of.” As used in the specification and the appended claims, the singular forms “a,” “an,” and “the” include plural referents unless the context dictates otherwise. Ratios, concentrations, amounts, and other numerical data can be expressed herein in a range format. Further, the endpoints of each of the ranges are significant both in relation to the other endpoint and independently of the other endpoint. There are many values disclosed herein, and each value is also disclosed as “about” that particular value in addition to the value itself. For example, if the value “10” is disclosed, then “about 10” is also disclosed. Ranges can be expressed herein as from “about” one particular value and to “about” another particular value. Similarly, when values are expressed as approximations, using the antecedent “about,” the particular value forms a further aspect. For example, if the value “about 10” is disclosed, then “10” is also disclosed. When a range is expressed, a further aspect includes from the one particular value and to the other particular value. For example, 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 disclosure, e.g., the phrase “x to y” includes the range from ‘x’ to ‘y’ as well as the range greater than ‘x’ and less than ‘y’. The range can also be expressed as an upper limit, e.g., ‘about x, y, z, or less’ and should be interpreted to include the specific ranges of ‘about x,’ ‘about y,’ and ‘about z’ as well as the ranges of ‘less than x,’ ‘less than y.’ and ‘less than z.’ Likewise, the phrase ‘about x, y, z, or greater’ should be interpreted to include the specific ranges of ‘about x,’ ‘about y,’ and ‘about z’ as well as the ranges of ‘greater than x,’ greater than y,’ and ‘greater than z.’ In addition, the phrase “about ‘x’ to ‘y’,” where ‘x’ and ‘y’ are numerical values, includes “about ‘x’ to about ‘y’.” Such a range format is used for convenience and brevity and, thus, should be interpreted flexibly to include not only the numerical values explicitly recited as the limits of the range but also to include all the individual numerical values or sub-ranges encompassed within that range as if each numerical value and sub-range is explicitly recited. To illustrate, a numerical range of “about 0.1% to 5%” should be interpreted to include not only the explicitly recited values of Attorney Docket No.103361-644WO1 about 0.1% to about 5% but also include individual values (e.g., about 1%, about 2%, about 3%, and about 4%) and the sub-ranges (e.g., about 0.5% to about 1.1%; about 5% to about 2.4%; about 0.5% to about 3.2%, and about 0.5% to about 4.4%, and other possible sub-ranges) within the indicated range. As used herein, the terms “about,” “approximate,” “at or about,” and “substantially” mean that the amount or value in question can be the exact value or a value that provides equivalent results or effects as recited in the claims or taught herein. That is, amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact but may be approximate, larger or smaller, as desired, reflecting tolerances, conversion factors, rounding, measurement error, and the like, and other factors known to those of skill in the art such that equivalent results or effects are obtained. In some circumstances, the value that provides equivalent results or effects cannot be reasonably determined. In such cases, as used herein, “about” and “at or about” mean the nominal value indicated ±10% variation unless otherwise indicated or inferred. In general, an amount, size, formulation, parameter, or other quantity or characteristic is “about,” “approximate,” or “at or about,” whether or not expressly stated to be such. Where “about,” “approximate,” or “at or about” is used before a quantitative value, the parameter also includes the specific quantitative value itself unless expressly stated otherwise. As used herein, the term “therapeutically effective amount” refers to an amount sufficient to achieve the desired therapeutic result or to have an effect on undesired symptoms but generally insufficient to cause adverse side effects. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors, including the disorder being treated and the severity of the disorder; the specific composition employed; the age, body weight, general health, sex, and diet of the patient; the time of administration; the route of administration; the rate of excretion of the specific compound employed; the duration of the treatment; drugs used in combination or coincidental with the particular compound employed and like factors within the knowledge and expertise of the health practitioner and which may be well known in the medical arts. In the case of treating a particular disease or condition, in some instances, the desired response can be inhibiting the progression of the disease or condition. This may involve only slowing the progression of the disease temporarily. However, in other instances, it may be desirable to halt the progression of the disease permanently. This can be monitored by routine diagnostic methods known to one of ordinary skill in the art for any particular disease. The desired response to treatment of the disease or condition can also be delaying the onset or even preventing the onset. Attorney Docket No.103361-644WO1 For example, it is well within the skill of the art to start doses of a compound at levels lower than those required to achieve the desired therapeutic effect and to increase the dosage gradually until the desired effect is achieved. If desired, the effective daily dose can be divided into multiple doses for administration. Consequently, single-dose compositions can contain such amounts or submultiples thereof to make up the daily dose. The individual physician can adjust the dosage in the event of any contraindications. It is generally preferred that a maximum dose of the pharmacological agents of the disclosure (alone or in combination with other therapeutic agents) be used, that is, the highest safe dose according to sound medical judgment. However, a patient may insist on a lower or tolerable dose for medical reasons, psychological reasons, or virtually any other reason. A response to a therapeutically effective dose of a disclosed compound or composition can be measured by determining the physiological effects of the treatment or medication, such as the decrease or lack of disease symptoms following the administration of the treatment or pharmacological agent. Other assays will be known to one of ordinary skill in the art and can be employed for measuring the level of the response. The amount of a treatment may be varied, for example, by increasing or decreasing the amount of a disclosed compound or pharmaceutical composition, changing the disclosed compound or pharmaceutical composition administered, changing the route of administration, changing the dosage timing, and so on. Dosage can vary and can be administered in one or more dose administrations daily for one or several days. Guidance can be found in the literature for appropriate dosages for given classes of pharmaceutical products. As used herein, “prevent” or “preventing” refers to precluding, averting, obviating, forestalling, stopping, or hindering something from happening, especially by advance action. Where reduce, inhibit, or prevent are used herein, unless specifically indicated otherwise, the use of the other two words is also expressly disclosed. As used herein, “optional” or “optionally” means that the subsequently described event or circumstance can or cannot occur. The description includes instances where said event or circumstance occurs and those where it does not. As used interchangeably herein, “subject,” “individual,” or “patient” can refer to a vertebrate organism, such as a mammal (e.g., human). “Subject” can also refer to a cell, a population of cells, a tissue, an organ, or an organism, preferably to a human and constituents thereof. Attorney Docket No.103361-644WO1 As used herein, “treating” and “treatment” generally refer to obtaining a desired pharmacological or physiological effect. The effect can be but does not necessarily have to be prophylactic in preventing or partially preventing a disease, symptom, or condition such as an infection. The effect can be therapeutic regarding a partial or complete cure of a disease, condition, symptom, or adverse effect attributed to the disease, disorder, or condition. The term “treatment” as used herein can include any treatment of a disorder in a subject, particularly a human. It can include any one or more of the following: (a) preventing the disease from occurring in a subject who may be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting the disease, i.e., arresting its development; and (c) relieving the disease, i.e., mitigating or ameliorating the disease or its symptoms or conditions. The term “treatment,” as used herein, can refer to both therapeutic treatment alone, prophylactic treatment alone, or both therapeutic and prophylactic treatment. Those in need of treatment (i.e., subjects in need thereof) can include those already with the disorder or those in which the disorder is to be prevented. As used herein, the term “treating” can include inhibiting the disease, disorder, or condition, e.g., impeding its progress, and relieving the disease, disorder, or condition, e.g., causing regression of the disease, disorder, or condition. Treating the disease, disorder, or condition can include ameliorating at least one symptom of the particular disease, disorder, or condition, even if the underlying pathophysiology is not affected, e.g., such as treating the pain of a subject by administration of an analgesic agent even though such agent does not treat the cause of the pain. As used herein, “dose,” “unit dose,” or “dosage” can refer to physically discrete units suitable for use in a subject, each unit containing a predetermined quantity of a disclosed compound or a pharmaceutical composition thereof calculated to produce the desired response or responses in association with its administration. As used herein, “therapeutic” can refer to treating, healing, or ameliorating a disease, disorder, condition, or side effect or decreasing the rate of advancement of a disease, disorder, condition, or side effect. As used herein, the term or phrase “effective,” “effective amount,” or “conditions effective to” refers to such amount or condition that is capable of performing the function or property for which an effective amount or condition is expressed. As will be pointed out below, the exact amount or particular condition required will vary from one aspect to another, depending on recognized variables such as the materials employed and the processing conditions observed. Thus, it is not always possible to specify an exact “effective amount” or “condition effective Attorney Docket No.103361-644WO1 to.” However, it should be understood that an appropriate, effective amount will be readily determined by one of ordinary skill in the art using only routine experimentation. Although the operations of representative aspects of the disclosed method may be described in a particular sequential order for convenient presentation, it should be understood that disclosed aspects can encompass an order of operations other than the particular sequential order disclosed. For example, operations described sequentially may, in some cases, be rearranged or performed concurrently. Further, descriptions and disclosures provided in association with one particular aspect are not limited to that aspect and may be applied to any aspect disclosed. As used herein, the term "substantially" means that the subsequently described event or circumstance completely occurs or that the subsequently described event or circumstance generally, typically, or approximately occurs. Still further, the term “substantially” can, in some aspects, refer to at least about 90 %, at least about 91 %, at least about 92 %, at least about 93 %, at least about 94 %, at least about 95 %, at least about 96 %, at least about 97 %, at least about 98 %, at least about 99 %, or about 100 % of the stated property, component, composition, or other condition for which substantially is used to characterize or otherwise quantify an amount. As used herein, the term “substantially,” in, for example, the context “substantially identical” or “substantially similar,” refers to a method or a system, or a component that is at least about 90%, at least about 91%, at least about 92%, at least about 93%, at least about 94%, at least about 95%, at least about 96%, at least about 97%, at least about 98%, at least about 99%, or about 100% by similar to the method, system, or the component it is compared to. Chemical Definitions Compounds are described using standard nomenclature. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of skill in the art to which this disclosure belongs. The compounds described herein include enantiomers, mixtures of enantiomers, diastereomers, tautomers, racemates, and other isomers, such as rotamers, as if each is specifically described unless otherwise indicated or otherwise excluded by context. It is to be understood that the compounds provided herein may contain chiral centers. Such chiral centers may be of either the (R) or (S) configuration. The compounds provided herein may either be enantiomerically pure or be diastereomeric or enantiomeric mixtures. It is to be understood that the chiral centers Attorney Docket No.103361-644WO1 of the compounds provided herein may undergo epimerization in vivo. As such, one of ordinary skill in the art will recognize that administering a compound in its (R) form is equivalent, for compounds that undergo epimerization in vivo, to administering the compound in its (S) form. Unless stated to the contrary, a formula with chemical bonds shown only as solid lines and not as wedges or dashed lines contemplates each possible isomer, e.g., each enantiomer, diastereomer, and meso compound, and a mixture of isomers, such as a racemic or scalemic mixture. Compounds described herein may contain one or more double bonds and, thus, potentially give rise to cis / trans (E / Z) isomers, as well as other conformational isomers unless stated to the contrary, all such possible isomers are contemplated, as well as mixtures of such isomers. Compounds described herein may also present as an equilibrium of tautomers. For example, ketones with an α-hydrogen can exist in an equilibrium of the keto form and the enol form. Likewise, amides with an N-hydrogen can exist in an equilibrium of the amide form and the imidic acid form. Unless stated to the contrary, all possible tautomers of the compounds described herein are contemplated. A dash that is not between two letters or symbols is used to indicate a point of attachment for a substituent. For example, -(C=O)NH2is attached through the carbon of the keto (C=O) group. The term “substituted,” as used herein, means that any one or more hydrogens on the designated atom or group are replaced with a moiety selected from the indicated group, provided that the designated atom’s normal valence is not exceeded and the resulting compound is stable. For example, when the substituent is oxo (i.e., =O), two hydrogens on the atom are replaced. For example, a pyridyl group substituted by oxo is a pyridine. Combinations of substituents and / or variables are permissible only if such combinations result in stable compounds or useful synthetic intermediates. A stable active compound refers to a compound that can be isolated and / or can be formulated into a form with a shelf life of at least one month. A stable manufacturing intermediate or precursor to an active compound is stable if it does not degrade within the period needed for reaction or other use. A stable moiety or substituent group is one that does not degrade, react, or fall apart within the period necessary for use. Non-limiting examples of unstable moieties are those that combine heteroatoms in an unstable arrangement, as typically known and identifiable to those of skill in the art. Attorney Docket No.103361-644WO1 Any suitable group may be present on a “substituted” or “optionally substituted” position that forms a stable molecule and meets the desired purpose of the disclosure and includes, but is not limited to: halo, nitro, cyano, azido, oxo, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2- C6 alkynyl, (C3-C6 cycloalkyl)(C0-C3 alkyl)-, (3- to 8-membered monocyclic or bicyclic heterocycle)-(C0-C6 alkyl)-, (6- to 10-membered monocyclic or bicyclic aryl)-(C0-C6 alkyl)-, (5- to 10-membered monocyclic or bicyclic heteroaryl)-(C0-C6alkyl)-, AxO-(C0-C6alkyl)-, AxS-(C0-C6alkyl)-, (AxAyN)-(C0-C6alkyl)-, AzC(O)-(C0-C6alkyl)-, AzC(N)-(C0-C6alkyl)-, and AzS(O)-(C0-C6 alkyl)-, and AzS(O)2-(C0-C6 alkyl)-, wherein Axand Ayare independently selected at each occurrence from Aa, AzC(O)-, AzC(N)-, AzS(O)-, and AzS(O)2-, each of which may be optionally substituted with one or more B groups as allowed by valency; wherein Azis independently selected at each occurrence from hydrogen, halo, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, (C3-C7cycloalkyl)-(C0-C3 alkyl)-, (4- to 6-membered heterocycle)-(C0-C3alkyl)-, (5- to 10-membered monocyclic or bicyclic aryl)-(C0-C3alkyl)-, (5- to 10-membered monocyclic or bicyclic heteroaryl)-(C0-C3 alkyl)-, -OAa, -SAa, and - NAaAb, each of which may be optionally substituted with one or more B groups as allowed by valency; wherein Aaand Abare independently selected at each occurrence from hydrogen, C1- C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, (C3-C7cycloalkyl)-(C0-C3alkyl)-, (4- to 6-membered heterocycle)-(C0-C3 alkyl)-, (5- to 10-membered monocyclic or bicyclic aryl)- (C0-C3alkyl)-, (5- to 10-membered monocyclic or bicyclic heteroaryl)-(C0-C3alkyl)-, each of which may be optionally substituted by one or more B groups as allowed by valency; and wherein B is independently selected at each occurrence from hydrogen, halo, nitro, cyano, azido, oxo, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, (C3-C6cycloalkyl)(C0- C3alkyl)-, (3- to 8-membered monocyclic or bicyclic heterocycle)-(C0-C6alkyl)-, (6- to 10- membered monocyclic or bicyclic aryl)-(C0-C6 alkyl)-, (5- to 10-membered monocyclic or bicyclic heteroaryl)-(C0-C6 alkyl)-, ApO-, ApS-, ApAqN-, AoC(O)-, AoC(O)-O-, AoC(O)-NAq-, AoS(O)2-, AoS(O)2-O-, and AoS(O)2-NAq-, wherein Aois independently selected at each occurrence from Ap, halo, ApO-, and ApAqN-, and wherein Apand Aqare independently selected at each occurrence from hydrogen, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, (C3-C6cycloalkyl)(C0-C3alkyl)-, (3- to 8-membered monocyclic or bicyclic heterocycle)-(C0- C6alkyl)-, (6- to 10-membered monocyclic or bicyclic aryl)-(C0-C6alkyl)-, and (5- to 10- membered monocyclic or bicyclic heteroaryl)-(C0-C6 alkyl)-. The terms for various functional groups as used herein are not intended to be limited to monovalent radicals and may include polyvalent radical groups as appropriate, such as Attorney Docket No.103361-644WO1 divalent, trivalent, tetravalent, pentavalent, and hexavalent groups, and the like, based on the position and location of such groups in the compounds described herein as would be readily understood by the skilled person in the context in which said functional groups are recited.As used herein, the symbol ” (which hereinafter can be referred to as “a point ofattachment bond”) denotes a bond that is a point of attachment between two chemical entities, one of which is depicted as being attached to the point of attachment bond and the other of which is not depicted as being attached to the point of attachment bond. For example, “ XY ” indicates that the chemical entity “XY” is bonded to another chemical entity via the point of attachment bond. Furthermore, the specific point of attachment to the non-depicted chemical entity can be specified by inference. For example, the compound CH3-R3, wherein R3XY is H or “ ” infers that when R3is “XY”, the point of attachment bond is the same bond as the bond by which R3is depicted as being bonded to CH3. “Halo” or “halogen” independently indicates any fluoro, chloro, bromo or iodo. The term “nitro,” as used herein, is represented by the formula —NO2. The term “cyano,” as used herein, is represented by the formula —CN The term “azido,” as used herein, is represented by the formula –N3. The term “oxo,” as used herein, is represented by the formula =O. “Alkyl” is a straight chain or branched saturated aliphatic hydrocarbon group. In certain aspects, the alkyl is C1-C2, C1-C3, or C1-C6(i.e., the alkyl chain can be 1, 2, 3, 4, 5, or 6 carbons in length). The specified ranges, as used herein, indicate an alkyl group with the length of each member of the range described as an independent species. For example, C1-C6alkyl, as used herein, indicates an alkyl group having 1, 2, 3, 4, 5, or 6 carbon atoms and is intended to mean that each of these is described as an independent species, and C1-C4alkyl, as used herein, indicates an alkyl group having 1, 2, 3, or 4 carbon atoms and is intended to mean that each of these is described as an independent species. When C0-Cnalkyl is used herein in conjunction with another group, for example (C3-C7cycloalkyl)C0-C4alkyl, or -C0-C4(C3-C7cycloalkyl), the indicated group, in this case cycloalkyl, is either directly bound by a single covalent bond (C0alkyl), or attached by an alkyl chain, in this case 1, 2, 3, or 4 carbon atoms. Alkyls can also be attached via other groups, such as heteroatoms, such as -O-C0-C4alkyl(C3-C7cycloalkyl). Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, Attorney Docket No.103361-644WO1 isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, tert-pentyl, neopentyl, n-hexyl, 2- methylpentane, 3-methylpentane, 2,2-dimethylbutane, and 2,3-dimethylbutane. In some aspects, the alkyl group is optionally substituted as described herein. “Haloalkyl” refers to an alkyl group that is substituted with one or more halo groups, e.g., fluoro, chloro, bromo, iodo, or combinations thereof. “Cycloalkyl” is a saturated or partially unsaturated mono- or multicyclic hydrocarbon ring system. When composed of two or more rings, the rings may be joined together in a fused or bridged fashion. Non-limiting examples of typical cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. In some aspects, the cycloalkyl group is optionally substituted as described herein. “Alkenyl” is a straight or branched chain aliphatic hydrocarbon group having one or more carbon-carbon double bonds, each of which is independently either cis or trans, that may occur at a stable point along the chain. Non-limiting examples include C2-C4alkenyl and C2-C6alkenyl (i.e., having 2, 3, 4, 5, or 6 carbons). The specified ranges as used herein indicate an alkenyl group, with each member of the range described as an independent species, as described above for the alkyl moiety. Examples of alkenyl include but are not limited to, ethenyl and propenyl. In one aspect, the alkenyl group is optionally substituted as described herein. “Alkynyl” is a straight or branched chain aliphatic hydrocarbon group having one or more carbon-carbon triple bonds that may occur at any stable point along the chain, for example, C2- C4alkynyl or C2-C6alkynyl (i.e., having 2, 3, 4, 5, or 6 carbons). The specified ranges, as used herein, indicate an alkynyl group, with each member of the range described as an independent species, as described above for the alkyl moiety. Examples of alkynyl include, but are not limited to, ethynyl, propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3- pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, and 5-hexynyl. In one aspect, the alkynyl group is optionally substituted as described herein. “Aryl” indicates an aromatic group containing only carbon in the aromatic ring or rings. In one aspect, the aryl group contains 1 to 3 separate or fused rings and is 6 to 14 or 18 ring atoms, without heteroatoms as ring members. When indicated, such aryl groups may be further substituted with carbon or non-carbon atoms or groups. Such substitution may include the fusion to a 4- to 7- or 5- to 7-membered saturated or partially unsaturated cyclic group that optionally contains 1, 2, or 3 heteroatoms independently selected from N, O, B, P, Si, and S, to form, for example, a 3,4-methylenedioxyphenyl group. Aryl groups include, for example, Attorney Docket No.103361-644WO1 phenyl and naphthyl, including 1-naphthyl and 2-naphthyl. In one aspect, aryl groups are pendant. An example of a pendant ring is a phenyl group substituted with a phenyl group. In one aspect, the aryl group is optionally substituted as described herein. The term “heterocycle” refers to saturated and partially saturated heteroatom-containing ring radicals, where the heteroatoms may be selected from N, O, and S. The term heterocycle includes monocyclic 3-12 members rings, as well as bicyclic 5-16 membered ring systems (which can include fused, bridged, or spiro bicyclic ring systems). It does not include rings containing -O-O-, -O-S-, and -S-S- portions. Examples of saturated heterocycle groups include saturated 4- to 7-membered monocyclic groups containing 1 to 4 nitrogen atoms [e.g., pyrrolidinyl, imidazolidinyl, piperidinyl, pyrrolinyl, azetidinyl, piperazinyl, and pyrazolidinyl]; saturated 4- to 6-membered monocyclic groups containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms [e.g., morpholinyl]; and saturated 3- to 6-membered heteromonocyclic groups containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms [e.g., thiazolidinyl]. Examples of partially saturated heterocycle radicals include, but are not limited to, dihydrothienyl, dihydropyranyl, dihydrofuryl, and dihydrothiazolyl. Examples of partially saturated and saturated heterocycle groups include, but are not limited to, pyrrolidinyl, imidazolidinyl, piperidinyl, pyrrolinyl, pyrazolidinyl, piperazinyl, morpholinyl, tetrahydropyranyl, thiazolidinyl, dihydrothienyl, 2,3-dihydro-benzo[1,4]dioxanyl, indolinyl, isoindolinyl, dihydrobenzothienyl, dihydrobenzofuryl, isochromanyl, chromanyl, 1,2- dihydroquinolyl, 1,2,3,4-tetrahydro-isoquinolyl, 1,2,3,4-tetrahydro-quinolyl, 2,3,4,4a,9,9a- hexahydro-1H-3-aza-fluorenyl, 5,6,7-trihydro-1,2,4-triazolo[3,4-a]isoquinolyl, 3,4-dihydro- 2H-benzo[1,4]oxazinyl, benzo[1,4]dioxanyl, 2,3,-dihydro-1H-benzo[d]isothazol-6-yl, dihydropyranyl, dihydrofuryl, and dihydrothiazolyl. Bicyclic heterocycle includes groups wherein the heterocyclic radical is fused with an aryl radical, and the point of attachment is the heterocycle ring. Bicyclic heterocycle also includes heterocyclic radicals that are fused with a carbocyclic radical. Representative examples include but are not limited to, partially unsaturated condensed heterocyclic groups containing 1 to 5 nitrogen atoms, for example, indoline and isoindoline, partially unsaturated condensed heterocyclic groups containing 1 to 2 oxygen atoms and 1 to 3 nitrogen atoms, partially unsaturated condensed heterocyclic groups containing 1 to 2 sulfur atoms and 1 to 3 nitrogen atoms, and saturated condensed heterocyclic groups containing 1 to 2 oxygen or sulfur atoms. In one aspect, the heterocycle group is optionally substituted as described herein. Attorney Docket No.103361-644WO1 “Heteroaryl” refers to a stable monocyclic, bicyclic, or multicyclic aromatic ring that contains from 1 to 4, or in some aspects 1, 2, or 3 heteroatoms selected from N, O, S, B, and P (and typically selected from N, O, and S) with remaining ring atoms being carbon, or a stable bicyclic or tricyclic system containing at least one 5, 6, or 7 membered aromatic ring which contains from 1 to 4, or in some aspects from 1 to 3 or from 1 to 2, heteroatoms selected from N, O, S, B, or P, with remaining ring atoms being carbon. In one aspect, the only heteroatom is nitrogen. In one aspect, the only heteroatom is oxygen. In one aspect, the only heteroatom is sulfur. Monocyclic heteroaryl groups typically have from 5 to 6 ring atoms. In some aspects, bicyclic heteroaryl groups are 8- to 10-membered heteroaryl groups, that is groups containing 8 or 10 ring atoms in which one 5-, 6-, or 7-membered aromatic ring which contains from 1 to 4 heteroatoms selected from N, O, S, B, or P is fused to a second aromatic or non-aromatic ring, wherein the point of attachment is an aromatic ring. When the total number of S and O atoms in the heteroaryl ring exceeds 1, these heteroatoms are not adjacent to one another within the ring. In one aspect, the total number of S and O atoms in the heteroaryl ring is not more than 2. In another aspect, the total number of S and O atoms in the heteroaryl ring is not more than 1. Examples of heteroaryl groups include, but are not limited to, pyridinyl, imidazolyl, imidazopyridinyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, furyl, thienyl, isoxazolyl, thiazolyl, oxadiazolyl, oxazolyl, isothiazolyl, pyrrolyl, quinolinyl, isoquinolinyl, tetrahydroisoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, cinnolinyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, triazolyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, and furopyridinyl. In one aspect, the heteroaryl group is optionally substituted as described herein. A “pharmaceutically acceptable salt” is a derivative of the disclosed compound in which the parent compound is modified by making inorganic and organic, pharmaceutically acceptable, acid or base addition salts thereof. The salts of the present compounds can be synthesized from a parent compound that contains a basic or acidic moiety by conventional chemical methods. Generally, such salts can be prepared by reacting free acid forms of these compounds with a stoichiometric amount of the appropriate base (such as Na, Ca, Mg, or K hydroxide, carbonate, bicarbonate, or the like) or by reacting free base forms of these compounds with a stoichiometric amount of the appropriate acid. Such reactions are typically carried out in water, an organic solvent, or in a mixture of the two. Generally, non-aqueous media like ether, ethyl acetate, ethanol, isopropanol, or acetonitrile are typical, where practicable. Salts of the present Attorney Docket No.103361-644WO1 compounds further include solvates of the compounds and of the compound salts. Examples of pharmaceutically acceptable salts include, but are not limited to, mineral or organic acid salts of basic residues such as amines; alkali or organic salts of acidic residues such as carboxylic acids; and the like. The pharmaceutically acceptable salts include salts that are acceptable for human consumption and the quaternary ammonium salts of the parent compound formed, for example, from inorganic or organic salts. Examples of such salts include but are not limited to, those derived from inorganic acids such as hydrochloric, hydrobromic, sulfuric, sulfamic, phosphoric, nitric, and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, pamoic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicyclic, mesylic, esylic, besylic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, ethane disulfonic, oxalic, isethionic, HOOC-(CH2)1-4-COOH, and the like, or using a different acid that produced the same counterion. Suitable counterions found in pharmaceutically acceptable salts described herein include but are not limited to, cations such as calcium, chloroprocaine, choline, diethanolamine, ethanolamine, ethylenediamine, meglumine, potassium, procaine, sodium, triethylamine, and zinc, and anions such as acetate, aspartate, benzenesulfonate, besylate, bicarbonate, bitartrate, bromide, camsylate, carbonate, chloride, citrate, decanoate, edetate, esylate, fumarate, gluceptate, gluconate, glutamate, glycolate, hexanoate, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methylsulfate, mucate, napsylate, nitrate, octanoate, oleate, pamoate, pantothenate, phosphate, polygalacturonate, propionate, salicylate, stearate, succinate, sulfate, tartrate, teoclate, and tosylate. Lists of additional suitable salts may be found, e.g., in Remington’s Pharmaceutical Sciences, 17thed., Mack Publishing Company, Easton, PA., p.1418 (1985). As used herein, the term “derivative” refers to a compound having a structure derived from the structure of a parent compound (e.g., a compound disclosed herein) and whose structure is sufficiently similar to those disclosed herein and based upon that similarity would be expected by one skilled in the art to exhibit the same or similar activities and utilities as the claimed compounds, or to induce, as a precursor, the same or similar activities and utilities as the claimed compound. Representative derivatives include, but are not limited to, salts, esters, amides, salts of esters or amides, and N-oxides of a parent compound. As used herein, substantially pure means sufficiently homogeneous to appear free of readily detectable impurities as determined by standard methods of analysis, such as thin layer chromatography (TLC), nuclear magnetic resonance (NMR), gel electrophoresis, high- Attorney Docket No.103361-644WO1 performance liquid chromatography (HPLC) and mass spectrometry (MS), gas- chromatography mass spectrometry (GC-MS), and similar, used by those of skill in the art to assess such purity, or sufficiently pure such that further purification would not detectably alter the physical and chemical properties, such as enzymatic and biological activities, of the substance. Both traditional and modern methods for purification of the compounds to produce substantially chemically pure compounds are known to those of skill in the art. A substantially chemically pure compound may, however, be a mixture of stereoisomers. Certain materials, compounds, compositions, and components disclosed herein can be obtained commercially or readily synthesized using techniques generally known to those of skill in the art. For example, the starting materials and reagents used in preparing the disclosed compounds and compositions are either available from commercial suppliers, such as Sigma-Aldrich (formally MilliporeSigma, Burlington, MA) or Thermo Fisher Scientific Inc. (Waltham, MA), or are prepared by methods known to those skilled in the art following procedures set forth in references such as Fieser and Fieser's Reagents for Organic Synthesis (John Wiley and Sons, 2007); Organic Reactions (John Wiley and Sons, 2004); March's Advanced Organic Chemistry, (John Wiley and Sons, 8thEdition); and Larock's Comprehensive Organic Transformations (John Wiley and Sons, 3rdedition, 2017). Compounds In one aspect, a compound is provided of Formula I-A or Formula I-B: or a pharmaceutically acceptable salt thereof, wherein all variables are as defined herein. Attorney Docket No.103361-644WO1 In some aspects of Formula I-A or Formula I-B, the dashed line represents a bond that can be present or absent, and when the bond is present, R1and R2can be cis or trans. In some aspects of Formula I-A or Formula I-B, A can be a fused bicyclic aryl or bicyclic heteroaryl ring optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, A and R1can be brought together with the carbon to which they are attached to form a tricyclic ring optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, B can be a five- to six-membered heteroaryl ring having 1, 2, or 3 ring heteroatoms selected from N, O, and S, wherein B can be optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, D can be a C5-C15aryl or C5-C15heteroaryl ring optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, R1and R2can be independently selected from H, OH, Cl, F, Br, I, CN, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, oxo, and C1-C6 alkyl or C1-C6 alkoxyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, R1can be a C1-C3 alkyl or C2-C3 alkenyl, optionally substituted with R9, also bound to A as allowed by valency. In some aspects of Formula I-A or Formula I-B, each R3can be independently selected from C1-C6 alkyl, C1-C6 cycloalkyl, C5-C15 aryl, C4-C15 heteroaryl, C3-C15 heterocycloalkyl, and C1- C15 heteroalkyl, any of which can be optionally substituted with one or more (for example, 1, 2, 3, or 4) groups selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, R9can be H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, CO2NH2, CO2NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, or C1-C6 alkyl or C1- C6alkoxyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups selected from Z as allowed by valency. Attorney Docket No.103361-644WO1 In some aspects of Formula I-A or Formula I-B, Z can be independently selected at each occurrence from halo, nitro, cyano, azido, oxo, C1-C6 alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6alkynyl, C3-C6cycloalkyl, 3- to 8-membered monocyclic or bicyclic heterocycle, 6- to 10-membered monocyclic or bicyclic aryl, 5- to 10-membered monocyclic or bicyclic heteroaryl, RxO-, RxS-, (RxRyN)-, RxO-C(O)-, RxS-C(O)-, (RxRyN)-C(O)-, RxO-S(O)2-, (RxRyN)-S(O)2-, RzC(O)-O-, RzC(O)-(RxN)-, RzS(O)2-O-, RzS(O)2-(RxN)-, RzC(O)-, RzS(O)-, and RzS(O)2-. In some aspects of Formula I-A or Formula I-B, Rxand Rycan be independently selected at each occurrence from hydrogen, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C7cycloalkyl, 4- to 6-membered heterocycle, 5- to 10-membered monocyclic or bicyclic aryl, 5- to 10-membered monocyclic or bicyclic heteroaryl. In some aspects of Formula I-A or Formula I-B, Rzcan be independently selected at each occurrence from hydrogen, halo, C1-C6alkyl, C1-C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3- C7cycloalkyl, 4- to 6-membered heterocycle, 5- to 10-membered monocyclic or bicyclic aryl, 5- to 10-membered monocyclic or bicyclic heteroaryl, -ORx, -SRx, and -NRxRy. In some aspects of Formula I-A, the dashed line represents a bond and thus can be represented by a formula selected from: wherein all variables are as defined herein. In some aspects of Formula I-A, the dashed line is absent and thus can be represented by the following formula: , wherein all variables are as defined herein. Attorney Docket No.103361-644WO1 In some aspects of Formula I-B, the dashed line represents a bond and thus can be represented by a formula selected from: wherein all variables are as defined herein. In some aspects of Formula I-B, the dashed line is absent and thus can be represented by the following formula: , wherein all variables are as defined herein. In some aspects of Formula I-B, the compound can be of a formula selected from: In some aspects of Formula I-A or Formula I-B, B can be a five-membered heteroaryl ring having 1, 2, or 3 ring heteroatoms selected from N, O, and S, wherein B can be optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. Attorney Docket No.103361-644WO1 In some aspects of Formula I-A or Formula I-B, B can be selected from furanyl, pyrrolyl, pyrazolyl, oxazolyl, imidazolyl, isoxazolyl, and triazolyl, each of which may be optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, B can be furanyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, B can be pyrrolyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, B can be pyrazolyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, B can be oxazolyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, B can be imidazolyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, B can be isoxazolyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, B can be triazolyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some particular aspects of Formula I-A or Formula I-B, B can be selected from: Attorney Docket No.103361-644WO1 In some aspects of Formula I-A or Formula I-B, A can be a fused bicyclic aryl or bicyclic heteroaryl ring having Formula II: wherein all variables are as defined herein. In some aspects of Formula II, each X can be independently CH or N. In some aspects of Formula II, R4and R5can be independently selected from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6alkyl or C1-C6alkoxyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups selected from Z as allowed by valency. In some aspects of Formula II, R4and R5can be independently selected from H, Cl, F, Br, I, CN, OH, and unsubstituted C1-C6alkyl or C1-C6alkoxy. In some aspects of Formula II, R4and R5can be independently selected from H, Cl, F, CN, OH, and methoxy. In some aspects of Formula II, R4and R5can be independently selected from F and methoxy. In some aspects of Formula II, each X in Formula II can be CH. In some aspects of Formula II, one X can be CH and the other two X’s can be N. In some aspects of Formula II, two X’s can be CH and the other X can be N. In some aspects of Formula II, all X’s can be N. In some aspects of Formula I-A or Formula I-B, A can be , wherein all variables are as defined herein. Attorney Docket No.103361-644WO1 In some aspects of Formula I-A or Formula I-B, A can be , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, A can be a fused bicyclic aryl or bicyclic heteroaryl ring having Formula III: III wherein all variables are as defined herein. In some aspects of Formula III, X can be independently CH or N. In some aspects of Formula III, R4can be selected from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6alkyl or C1-C6 alkoxyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula III, R4can be selected from H, Cl, F, Br, I, CN, OH, and unsubstituted C1-C6alkyl or C1-C6alkoxy. In some aspects of Formula III, R4can be selected from H, Cl, F, CN, OH, and methoxy. In aspects of Formula III, R4can be selected from F and methoxy. In some aspects of Formula III, each X can be N. In some aspects of Formula III, two X’s can be CH and the other X can be N. In some aspects of Formula III, two X’s can be N and the other X can be CH. In some aspects of Formula I-A or Formula I-B, A can be a bicyclic aryl or bicyclic heteroaryl that together with R1forms a tricyclic ring. When R1is a CH2, this can be represented by Formula IX, X, XI, or XII. Attorney Docket No.103361-644WO1 In some aspects of Formula I-A or Formula I-B, A can be Formula IX: wherein all variables are as defined herein. In some aspects of Formula IX, X can be CH, N, or CR8. In some aspects of Formula IX, R4and R5can be independently selected from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6 alkyl or C1-C6 alkoxyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula IX, R8can be Cl, F, CN, OH, OCH3, CH3, or NH2. In some aspects of Formula IX, R9can be H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, or C1-C6 alkyl or C1-C6 alkoxyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, A can be Formula X: wherein all variables are as defined herein. In some aspects of Formula X, each X can be independently CH, N, or CR8. Attorney Docket No.103361-644WO1 In some of Formula X, R4and R5can be independently selected from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6alkyl or C1-C6alkoxyl optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula X, R8can be independently Cl, F, CN, OH, OCH3, CH3, or NH2. In some aspects of Formula X, R9can be H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, or C1-C6alkyl or C1-C6alkoxy optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula I-A or Formula I-B, A is , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, A can be , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, A can be Attorney Docket No.103361-644WO1 , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, A can be , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, A can be Formula XI: wherein all variables are as defined herein. In some aspects of Formula XI, each X can be independently CH, N, or CR8. In some aspects of Formula XI, R4and R5can be independently selected from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6alkyl or C1-C6alkoxy optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. Attorney Docket No.103361-644WO1 In some aspects of Formula XI, each R8can be independently Cl, F, CN, OH, OCH3, CH3, or NH2. In some aspects of Formula XI, R9can be H or C1-C6alkyl. In some aspects of Formula I-A or Formula I-B, A can be Formula XII: XII wherein all variables are as defined herein. In some aspects of Formula XII, each X can be independently CH, N, or CR8. In some aspects of Formula XII, R4and R5can be independently selected from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6alkyl or C1-C6alkoxy optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formula XII, each R8can be independently Cl, F, CN, OH, OCH3, CH3, or NH2. In some aspects of Formula XII, R9can be H or C1-C6 alkyl. In some aspects of Formula I-A or Formula I-B, A can be wherein each of R4, R5, R8, and R9can be independently selected from Cl, F, CN, OH, OCH3, CH3, or NH2. In some aspects, R9is H or CH3. In some aspects of Formula I-A or Formula I-B, A can be Attorney Docket No.103361-644WO1 , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, A can be , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, A can be , wherein all variables are as defined herein. In some aspects of Formula IX, X, XI, and XII, R5can be F. In some aspects of Formula I-A or Formula I-B, A is selected from: Attorney Docket No.103361-644WO1 In some aspects of Formula I-A or Formula I-B, R1and R2are independently selected from H, F, OH, and NH2. In some aspects of Formula I-A or Formula I-B, R2is NH2. In some aspects of Formula I-A or Formula I-B, R2is H or OH. In some aspects of Formula I-A or Formula I- B, R1is H or OH. In some aspects of Formula I-A or Formula I-B, R2is oxo (i.e., =O). In some aspects of Formula I-A or Formula I-B, R1is oxo (i.e., =O). Incorporation of a hydroxyl substituent (at R1or R2) reduces lipophilicity by ca. 1.5 CLogP units and has been shown in some cases to impact hERG inhibition and other properties. In some aspects of Formula I-A or Formula from: In some aspects of Formula I-A or Formula I-B, D is aryl or heteroaryl ring having Formulae IV-VIII or XIII. Attorney Docket No.103361-644WO1 VIII XIII wherein all variables are as defined herein. In some aspects of Formulae IV-VIII or XIII, each X can be independently selected from CH or N. In some aspects of Formulae IV-VIII or XIII, each Y can be independently selected from O, S, NH, or CH2. In some aspects of Formulae IV-VIII or XIII, R6and R7can be independently selected from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6alkyl or C1-C6alkoxy optionally substituted with one or more (for example, 1, 2, 3, or 4) groups independently selected from Z as allowed by valency. In some aspects of Formulae IV-VIII or XIII, R6and R7can be independently selected from H, Cl, F, Br, I, CN, OH, and unsubstituted C1-C6alkyl or C1-C6alkoxy. In some aspects of Formulae IV-VIII or XIII, R6and R7can be independently selected from H, Cl, F, CN, OH, and methoxy. In some aspects of Formulae IV-VIII or XIII, R6and R7can be independently selected from F and methoxy. In some aspects of Formulae IV-VIII or XIII, R6and R7can be both H. In some aspects of Formulae IV-VIII or XIII, both Y can be O. In some aspects of Formulae IV-VIII or XIII, one Y can be S and the other can be O. In some aspects of Formulae IV-VIII or XIII, one Y can be NH and the other can be O. In some aspects of Formula I-A or Formula I-B, D can be , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, D can be: Attorney Docket No.103361-644WO1 , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, D can be , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, D can be , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, D can be , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, D can be , Attorney Docket No.103361-644WO1 wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, D can be , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, D can be , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, D can be , wherein all variables are as defined herein. In some aspects of Formula I-A or Formula I-B, D can be selected from: In some independent occurrences of Z, Z can be selected from fluoro, chloro, bromo, and iodo. In some independent occurrences of Z, Z can be cyano. In some independent occurrences of Z, Z can be azido. In some independent occurrences of Z, Z can be oxo. Attorney Docket No.103361-644WO1 In some independent occurrences of Z, Z can be selected from methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n-pentyl, isopentyl, tert-pentyl, neopentyl, n- hexyl, 2-methylpentane, 3-methylpentane, 2,2-dimethylbutane, and 2,3-dimethylbutane. In some independent occurrences of Z, Z can be selected from trifluoromethyl, trifluoroethyl, and hexafluoroisopropyl. In some independent occurrences of Z, Z can be selected from ethenyl and propenyl. In some independent occurrences of Z, Z can be selected from ethynyl, propynyl, and propargyl. In some independent occurrences of Z, Z can be selected from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl. In some independent occurrences of Z, Z can be selected from pyrrolidinyl, imidazolidinyl, piperidinyl, pyrrolinyl, azetidinyl, piperazinyl, pyrazolidinyl, morpholinyl, tetrahydrofuranyl, tetrahydropyranyl, thiazolidinyl, indolinyl, and isoindolinyl. In some independent occurrences of Z, Z can be selected from phenyl, 1-naphthyl, and 2- naphthyl. In some independent occurrences of Z, Z can be selected from pyridinyl, imidazolyl, imidazopyridinyl, pyrimidinyl, pyrazolyl, triazolyl, pyrazinyl, furyl, thienyl, isoxazolyl, thiazolyl, oxadiazolyl, oxazolyl, pyrrolyl, quinolinyl, isoquinolinyl, indolyl, benzimidazolyl, benzofuranyl, indazolyl, indolizinyl, phthalazinyl, pyridazinyl, triazinyl, isoindolyl, pteridinyl, purinyl, thiadiazolyl, furazanyl, benzofurazanyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, quinazolinyl, quinoxalinyl, naphthyridinyl, and furopyridinyl. In some independent occurrences of Z, Z can be RxO-, wherein Rxcan be selected from hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z can be RxS-, wherein Rxcan be selected from hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z can be (RxRyN)-, wherein Rxand Rycan be independently selected from hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. Attorney Docket No.103361-644WO1 In some independent occurrences of Z, Z can be RxO-C(O)-, wherein Rxcan be selected from hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z can be RxS-C(O)-, wherein Rxcan be selected from hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z can be (RxRyN)-C(O)-, wherein Rxand Rycan be independently selected from hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z can be RxO-S(O)2-, wherein Rxcan be selected from hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z can be (RxRyN)-S(O)2-, wherein Rxand Rycan be independently selected from hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z can be RzC(O)-O-, wherein Rzcan be selected from hydrogen, chloro, bromo, -OH, -NH2, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z can be RzC(O)-(RxN)-, wherein Rxcan be selected from hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl, and wherein Rzis selected from hydrogen, chloro, bromo, -OH, -NH2, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z can be RzS(O)2-O-, wherein Rzcan be selected from hydrogen, chloro, bromo, -OH, -NH2, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z can be RzS(O)2-(RxN)-, wherein Rxcan be selected from hydrogen, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl, and wherein Rzis selected from hydrogen, chloro, bromo, -OH, -NH2, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. Attorney Docket No.103361-644WO1 In some independent occurrences of Z, Z can be RzC(O)-, wherein Rzcan be selected from hydrogen, chloro, bromo, -OH, -NH2, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z can be RzS(O)-, wherein Rzcan be selected from hydrogen, chloro, bromo, -OH, -NH2, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In some independent occurrences of Z, Z is RzS(O)2-, wherein Rzis selected from hydrogen, chloro, bromo, -OH, -NH2, methyl, ethyl, isopropyl, trifluoromethyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and phenyl. In another aspect, a compound is provided selected from: 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)furan-2-yl)piperidin-1-yl)ethyl)-1,5-naphthyridine (example 1); 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)furan-2-yl)piperidin-1-yl)ethyl)-7-fluoro-2- methoxy-1,5-naphthyridine (example 2); 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)furan-2-yl)-2H- benzo[b][1,4]oxazin-3(4H)-one (example 3); 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-pyrrol-2-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 4); 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrrol-2-yl)piperidin-1-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 5); 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-pyrrol-2-yl)- 2H-benzo[b][1,4]oxazin-3(4H)-one (example 6); 5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-2-(p-tolyl)oxazole (example 7); 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)ethyl)piperidin-4-yl)oxazole (example 8); 3-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-5-(p-tolyl)isoxazole (example 9); 5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)ethyl)piperidin-4-yl)isoxazole (example 10); Attorney Docket No.103361-644WO1 6-(3-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)isoxazol-5-yl)- 2H-benzo[b][1,4]oxazin-3(4H)-one (example 11); 5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-3-(p-tolyl)isoxazole (example 12); 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)ethyl)piperidin-4-yl)isoxazole (example 13); 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)isoxazol-3-yl)- 2H-benzo[b][1,4]oxazin-3(4H)-one (example 14); 7-fluoro-2-methoxy-8-(2-(4-(1-(p-tolyl)-1H-1,2,3-triazol-4-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 15); 8-(2-(4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-4-yl)piperidin-1-yl)ethyl)- 7-fluoro-2-methoxy-1,5-naphthyridine (example 16); 7-fluoro-2-methoxy-8-(2-(4-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 17); 8-(2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)ethyl)- 7-fluoro-2-methoxy-1,5-naphthyridine (example 18); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 19); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (example 20); 8-(2-(4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)ethyl)-7-fluoro-2- methoxy-1,5-naphthyridine (example 21); 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 22); 7-fluoro-2-methoxy-8-(2-(4-(4-(p-tolyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 23); 8-(2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-1-yl)piperidin-1-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 24); Attorney Docket No.103361-644WO1 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-pyrazol-4- yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 25); 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-(4-(4-(p-tolyl)-1H-1,2,3-triazol-1- yl)piperidin-1-yl)ethan-1-ol (example 26); 2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)-1-(3- fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol (example 27); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl)piperidin-4-yl)-1H- 1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 28); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl)piperidin-4-yl)-1H- 1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (example 29); 2-(4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)-1-(3-fluoro-6-methoxy- 1,5-naphthyridin-4-yl)ethan-1-ol (example 30); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 4-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (example 31); 7-fluoro-2-methoxy-8-(2-((2r,5r)-5-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2-yl)ethyl)- 1,5-naphthyridine (example 32); 8-(2-((2r,5r)-5-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2- yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine (example 33); 6-(1-((2r,5r)-2-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)-1,3-dioxan-5-yl)-1H- 1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 34); 8-(2-((2r,5r)-5-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 35); (S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-((2r,5S)-5-(4-(p-tolyl)-1H-1,2,3-triazol- 1-yl)-1,3-dioxan-2-yl)ethan-1-ol (example 36); (S)-1-((2r,5S)-5-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan- 2-yl)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol (example 37); 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-hydroxyethyl)-1,3- dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 38); Attorney Docket No.103361-644WO1 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-hydroxyethyl)-1,3- dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (example 39); (S)-1-((2r,5S)-5-(4-(5,6-dichloropyrazin-2-yl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2-yl)-2-(3- fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol (example 40); 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-hydroxyethyl)-1,3- dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (example 41); 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-pyrazol-3-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 42); 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-3-yl)piperidin-1-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 43); 7-fluoro-2-methoxy-8-(2-(4-(1-methyl-5-(p-tolyl)-1H-pyrazol-3-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 44, first regioisomer); 7-fluoro-2-methoxy-8-(2-(4-(1-methyl-3-(p-tolyl)-1H-pyrazol-5-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 44, second regioisomer); 6-(4-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 45); and 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl)piperidin-4-yl)-1H- 1,2,3-triazol-4-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (example 46); or a pharmaceutically acceptable salt thereof. The present disclosure also includes compounds described herein with at least one desired isotopic substitution of an atom at an amount above the natural abundance of the isotope, i.e., enriched. Examples of isotopes that can be incorporated into compounds of the present disclosure include isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorous, fluorine, and chlorine, such as2H,3H,11C,13C,15N,17O,18O,18F,31P, 32P,35S,36Cl, and125I, respectively. In one aspect, isotopically labeled compounds can be used in metabolic studies (with14C), reaction kinetic studies (with, for example,2H or3H), detection or imaging techniques, such as positron emission tomography (PET) or single-photon emission computed tomography (SPECT) including drug and substrate tissue distribution assays, or in radioactive treatment of patients. In particular, an18F-labeled compound may be particularly desirable for PET or SPECT studies. Attorney Docket No.103361-644WO1 Isotopically labeled compounds of this disclosure and prodrugs thereof can generally be prepared by carrying out the procedures disclosed herein by substituting a readily available isotopically labeled reagent for a non-isotopically labeled reagent. By way of general example and without limitation, isotopes of hydrogen, for example, deuterium (2H) and tritium (3H), may optionally be used anywhere in described structures that achieve the desired result. Alternatively, or in addition, isotopes of carbon, e.g.,13C and14C, may be used. In one aspect, the isotopic substitution is replacing hydrogen with deuterium at one or more locations on the molecule to improve the performance of the molecule as a drug, for example, the pharmacodynamics, pharmacokinetics, biodistribution, half-life, stability, AUC, Tmax, Cmax, etc. For example, the deuterium can be bound to carbon in the allocation of bond breakage during metabolism (an alpha-deuterium kinetic isotope effect) or next to or near the site of bond breakage (a beta-deuterium kinetic isotope effect). Isotopic substitutions, for example, deuterium substitutions, can be partial or complete. Partial deuterium substitution means that at least one hydrogen is substituted with deuterium. In certain aspects, the isotope is 80, 85, 90, 95, or 99% or more enriched in an isotope at any location of interest. In some aspects, deuterium is 80, 85, 90, 95, or 99% enriched at a desired location. Unless otherwise stated, enrichment at any point is above natural abundance and, in an aspect, is enough to alter a detectable property of the compounds as a drug in a human. The compounds of the present disclosure may form a solvate with solvents (including water). Therefore, in one aspect, the disclosure includes a solvated form of the active compound. The term “solvate” refers to a molecular complex of a compound of the present disclosure (including a salt thereof) with one or more solvent molecules. Non-limiting examples of solvents are water, ethanol, dimethyl sulfoxide, acetone, and other common organic solvents. The term “hydrate” refers to a molecular complex comprising a disclosed compound and water. Pharmaceutically acceptable solvates in accordance with the disclosure include those wherein the solvent of crystallization may be isotopically substituted, e.g., D2O, d6-acetone, or d6- DMSO. A solvate can be in a liquid or solid form. A “prodrug,” as used herein, means a compound that, when administered to a host in vivo, is converted into a parent drug. As used herein, the term “parent drug” means any of the presently described compounds herein. Prodrugs can be used to achieve any desired effect, including to enhance the properties of the parent drug or to improve the pharmaceutic or pharmacokinetic properties of the parent, including increasing the half-life of the drug in vivo. Prodrug strategies Attorney Docket No.103361-644WO1 provide choices in modulating the conditions for in vivo generation of the parent drug. Non- limiting examples of prodrug strategies include covalent attachment of removable groups or removable portions of groups, for example, but not limited to, acylating, phosphorylation, phosphonylation, phosphoramidate derivatives, amidation, reduction, oxidation, esterification, alkylation, other carboxy derivatives, sulfoxy or sulfone derivatives, carbonylation, or anhydrides, among others. In certain aspects, the prodrug renders the parent compound more lipophilic. In certain aspects, a prodrug can be provided that has several prodrug moieties in a linear, branched, or cyclic manner. For example, non-limiting aspects include the use of a divalent linker moiety such as a dicarboxylic acid, amino acid, diamine, hydroxycarboxylic acid, hydroxyamine, di-hydroxy compound, or other compounds that have at least two functional groups that can link the parent compound with another prodrug moiety and are typically biodegradable in vivo. In some aspects, 2, 3, 4, or 5 prodrug biodegradable moieties are covalently bound in a sequence, branched, or cyclic fashion to the parent compound. Non- limiting examples of prodrugs according to the present disclosure are formed with: a carboxylic acid on the parent drug and a hydroxylated prodrug moiety to form an ester; a carboxylic acid on the parent drug and an amine prodrug to form an amide; an amino on the parent drug and a carboxylic acid prodrug moiety to form an amide; an amino on the parent drug and a sulfonic acid to form a sulfonamide; a sulfonic acid on the parent drug and an amino on the prodrug moiety to form a sulfonamide; a hydroxyl group on the parent drug and a carboxylic acid on the prodrug moiety to form an ester; a hydroxyl on the parent drug and a hydroxylated prodrug moiety to form an ester; a phosphonate on the parent drug and a hydroxylated prodrug moiety to form a phosphonate ester; a phosphoric acid on the parent drug and a hydroxylated prodrug moiety to form a phosphate ester; a hydroxyl on the parent drug and a phosphonate on the prodrug to form a phosphonate ester; a hydroxyl on the parent drug and a phosphoric acid prodrug moiety to form a phosphate ester; a carboxylic acid on the parent drug and a prodrug of the structure HO-(CH2)2-O-(C2-24alkyl) to form an ester; a carboxylic acid on the parent drug and a prodrug of the structure HO-(CH2)2-S-(C2-24 alkyl) to form a thioester; a hydroxyl on the parent drug and a prodrug of the structure HO-(CH2)2-O-(C2-24 alkyl) to form an ether; a hydroxyl on the parent drug and a prodrug of the structure HO-(CH2)2-O-(C2-24alkyl) to form an thioether; and a carboxylic acid, oxime, hydrazide, hydrazine, amine or hydroxyl on the parent compound and a prodrug moiety that is a biodegradable polymer or oligomer including but not limited to polylactic acid, polylactide-co-glycolide, polyglycolide, polyethylene glycol, polyanhydride, polyester, polyamide, or a peptide. Attorney Docket No.103361-644WO1 In some aspects, a prodrug is provided by attaching a natural or non-natural amino acid to an appropriate functional moiety on the parent compound, for example, oxygen, nitrogen, or sulfur, and typically oxygen or nitrogen, usually in a manner such that the amino acid is cleaved in vivo to provide the parent drug. The amino acid can be used alone or covalently linked (straight, branched, or cyclic) to one or more other prodrug moieties to modify the parent drug to achieve the desired performance, such as increased half-life, lipophilicity, or other drug delivery or pharmacokinetic properties. The amino acid can be any compound with an amino group and a carboxylic acid, which includes an aliphatic amino acid, alkyl amino acid, aromatic amino acid, heteroaliphatic amino acid, heteroalkyl amino acid, heterocyclic amino acid, or heteroaryl amino acid. Pharmaceutical Compositions The compounds as described herein can be administered by any suitable method and technique presently or prospectively known to those skilled in the art. For example, the active components described herein can be formulated in a physiologically- or pharmaceutically-acceptable form and administered by any suitable route known in the art, including, for example, oral and parenteral routes of administering. As used herein, the term “parenteral” includes subcutaneous, intradermal, intravenous, intramuscular, intraperitoneal, and intrasternal administration, such as by injection. Administration of the active components of their compositions can be a single administration or at continuous and distinct intervals as can be readily determined by a person skilled in the art. Compositions, as described herein, comprising an active compound and a pharmaceutically acceptable carrier or excipient of some sort, may be useful in a variety of medical and non- medical applications. For example, pharmaceutical compositions comprising an active compound and an excipient may be useful for the treatment or prevention of an infection in a subject in need thereof. "Pharmaceutically acceptable carrier" (sometimes referred to as a "carrier") means a carrier or excipient that is useful in preparing a pharmaceutical or therapeutic composition that is generally safe and non-toxic and includes a carrier that is acceptable for veterinary and / or human pharmaceutical or therapeutic use. The terms "carrier" or "pharmaceutically acceptable carrier" can include, but are not limited to, phosphate-buffered saline solution, water, emulsions (such as an oil / water or water / oil emulsion) and / or various types of wetting agents. As used herein, the term "carrier" encompasses, but is not limited to, any excipient, diluent, filler, salt, Attorney Docket No.103361-644WO1 buffer, stabilizer, solubilizer, lipid, stabilizer, or other material well-known in the art for use in pharmaceutical formulations and as described further herein. “Excipients” include any and all solvents, diluents or other liquid vehicles, dispersion or suspension aids, surface active agents, isotonic agents, thickening or emulsifying agents, preservatives, solid binders, lubricants, and the like, as suited to the particular dosage form desired. General considerations in formulation and / or manufacture can be found, for example, in Remington's Pharmaceutical Sciences, Sixteenth Edition, E. W. Martin (Mack Publishing Co., Easton, Pa., 1980), and Remington: The Science and Practice of Pharmacy, 21st Edition (Lippincott Williams & Wilkins, 2005). Representative excipients include but are not limited to, any non-toxic, inert solid, semisolid, or liquid filler, diluent, encapsulating material, or formulation auxiliary of any type. Some examples of materials which can serve as excipients include, but are not limited to, sugars such as lactose, glucose, and sucrose; starches such as corn starch and potato starch; cellulose and its derivatives such as sodium carboxymethyl cellulose, ethyl cellulose, and cellulose acetate; powdered tragacanth; malt; gelatin; talc; excipients such as cocoa butter and suppository waxes; oils such as peanut oil, cottonseed oil; safflower oil; sesame oil; olive oil; corn oil and soybean oil; glycols such as propylene glycol; esters such as ethyl oleate and ethyl laurate; agar; detergents such as Tween 80; buffering agents such as magnesium hydroxide and aluminum hydroxide; alginic acid; pyrogen-free water; isotonic saline; Ringer's solution; ethyl alcohol; and phosphate buffer solutions, as well as other non-toxic compatible lubricants such as sodium lauryl sulfate and magnesium stearate, as well as coloring agents, releasing agents, coating agents, sweetening, flavoring and perfuming agents, preservatives and antioxidants can also be present in the composition, according to the judgment of the formulator. As would be appreciated by one of skill in this art, the excipients may be chosen based on what the composition is useful for. For example, with a pharmaceutical composition or cosmetic composition, the choice of the excipient will depend on the route of administration, the agent being delivered, the time course of delivery of the agent, etc., and can be administered to humans and / or to animals, orally, rectally, parenterally, intracisternally, intravaginally, intranasally, intraperitoneally, topically (as by powders, creams, ointments, or drops), buccally, or as an oral or nasal spray. In some aspects, the active compounds disclosed herein are administered topically. Representative diluents include calcium carbonate, sodium carbonate, calcium phosphate, dicalcium phosphate, calcium sulfate, calcium hydrogen phosphate, sodium phosphate lactose, Attorney Docket No.103361-644WO1 sucrose, cellulose, microcrystalline cellulose, kaolin, mannitol, sorbitol, inositol, sodium chloride, dry starch, cornstarch, powdered sugar, etc., and combinations thereof. Representative granulating and / or dispersing agents include potato starch, corn starch, tapioca starch, sodium starch glycolate, clays, alginic acid, guar gum, citrus pulp, agar, bentonite, cellulose and wood products, natural sponge, cation-exchange resins, calcium carbonate, silicates, sodium carbonate, cross-linked poly(vinyl-pyrrolidone) (crospovidone), sodium carboxymethyl starch (sodium starch glycolate), carboxymethyl cellulose, cross-linked sodium carboxymethyl cellulose (croscarmellose), methylcellulose, pregelatinized starch (starch 1500), microcrystalline starch, water-insoluble starch, calcium carboxymethyl cellulose, magnesium aluminum silicate (Veegum), sodium lauryl sulfate, quaternary ammonium compounds, etc., and combinations thereof. Representative surface active agents and / or emulsifiers include natural emulsifiers (e.g. acacia, agar, alginic acid, sodium alginate, tragacanth, chondrux, cholesterol, xanthan, pectin, gelatin, egg yolk, casein, wool fat, cholesterol, wax, and lecithin), colloidal clays (e.g. bentonite [aluminum silicate] and Veegum [magnesium aluminum silicate]), long chain amino acid derivatives, high molecular weight alcohols (e.g. stearyl alcohol, cetyl alcohol, oleyl alcohol, triacetin monostearate, ethylene glycol distearate, glyceryl monostearate, and propylene glycol monostearate, polyvinyl alcohol), carbomers (e.g. carboxy polymethylene, polyacrylic acid, acrylic acid polymer, and carboxy vinyl polymer), carrageenan, cellulosic derivatives (e.g. carboxymethylcellulose sodium, powdered cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose), sorbitan fatty acid esters (e.g. polyoxyethylene sorbitan monolaurate [Tween 20], polyoxyethylene sorbitan [Tween 60], polyoxyethylene sorbitan monooleate [Tween 80], sorbitan monopalmitate [Span 40], sorbitan monostearate [Span 60], sorbitan tristearate [Span 65], glyceryl monooleate, sorbitan monooleate [Span 80]), polyoxyethylene esters (e.g. polyoxyethylene monostearate [Myrj 45], polyoxyethylene hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate, and Solutol), sucrose fatty acid esters, polyethylene glycol fatty acid esters (e.g. Cremophor), polyoxyethylene ethers, (e.g. polyoxyethylene lauryl ether [Brij 30]), poly(vinyl- pyrrolidone), diethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium lauryl sulfate, Pluronic F 68, Poloxamer 188, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, docusate sodium, etc. and / or combinations thereof. Representative binding agents include starch (e.g., cornstarch and starch paste), gelatin, sugars (e.g., sucrose, glucose, dextrose, dextrin, molasses, Attorney Docket No.103361-644WO1 lactose, lactitol, mannitol, etc.), natural and synthetic gums (e.g., acacia, sodium alginate, extract of Irish moss, panwar gum, ghatti gum, mucilage of isapol husks, carboxymethylcellulose, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, cellulose acetate, poly(vinyl-pyrrolidone), magnesium aluminum silicate (Veegum), and larch arabogalactan), alginates, polyethylene oxide, polyethylene glycol, inorganic calcium salts, silicic acid, polymethacrylates, waxes, water, alcohol, etc., and / or combinations thereof. Representative preservatives include antioxidants, chelating agents, antimicrobial preservatives, antifungal preservatives, alcohol preservatives, acidic preservatives, and other preservatives. Representative antioxidants include alpha tocopherol, ascorbic acid, ascorbyl palmitate, butylated hydroxyanisole, butylated hydroxytoluene, monothioglycerol, potassium metabisulfite, propionic acid, propyl gallate, sodium ascorbate, sodium bisulfite, sodium metabisulfite, and sodium sulfite. Representative chelating agents include ethylenediaminetetraacetic acid (EDTA) and salts and hydrates thereof (e.g., sodium edetate, disodium edetate, trisodium edetate, calcium disodium edetate, dipotassium edetate, and the like), citric acid and salts and hydrates thereof (e.g., citric acid monohydrate), fumaric acid and salts and hydrates thereof, malic acid and salts and hydrates thereof, phosphoric acid and salts and hydrates thereof, and tartaric acid and salts and hydrates thereof. Representative antimicrobial preservatives include benzalkonium chloride, benzethonium chloride, benzyl alcohol, bronopol, cetrimide, cetylpyridinium chloride, chlorhexidine, chlorobutanol, chlorocresol, chloroxylenol, cresol, ethyl alcohol, glycerin, hexetidine, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric nitrate, propylene glycol, and thimerosal. Representative antifungal preservatives include butyl paraben, methyl paraben, ethyl paraben, propyl paraben, benzoic acid, hydroxybenzoic acid, potassium benzoate, potassium sorbate, sodium benzoate, sodium propionate, and sorbic acid. Representative alcohol preservatives include ethanol, polyethylene glycol, phenol, phenolic compounds, bisphenol, chlorobutanol, hydroxybenzoate, and phenylethyl alcohol. Representative acidic preservatives include vitamin A, vitamin C, vitamin E, beta-carotene, citric acid, acetic acid, dehydroacetic acid, ascorbic acid, sorbic acid, and phytic acid. Other preservatives include tocopherol, tocopherol acetate, deteroxime mesylate, cetrimide, butylated Attorney Docket No.103361-644WO1 hydroxyanisol (BHA), butylated hydroxytoluene (BHT), ethylenediamine, sodium lauryl sulfate (SLS), sodium lauryl ether sulfate (SLES), sodium bisulfite, sodium metabisulfite, potassium sulfite, potassium metabisulfite, Glydant Plus, Phenonip, methylparaben, Germall 115, Germaben II, Neolone, Kathon, and Euxyl. In certain aspects, the preservative is an anti- oxidant. In other aspects, the preservative is a chelating agent. Representative buffering agents include citrate buffer solutions, acetate buffer solutions, phosphate buffer solutions, ammonium chloride, calcium carbonate, calcium chloride, calcium citrate, calcium glubionate, calcium gluceptate, calcium gluconate, D-gluconic acid, calcium glycerophosphate, calcium lactate, propanoic acid, calcium levulinate, pentanoic acid, dibasic calcium phosphate, phosphoric acid, tribasic calcium phosphate, calcium hydroxide phosphate, potassium acetate, potassium chloride, potassium gluconate, potassium mixtures, dibasic potassium phosphate, monobasic potassium phosphate, potassium phosphate mixtures, sodium acetate, sodium bicarbonate, sodium chloride, sodium citrate, sodium lactate, dibasic sodium phosphate, monobasic sodium phosphate, sodium phosphate mixtures, tromethamine, magnesium hydroxide, aluminum hydroxide, alginic acid, pyrogen-free water, isotonic saline, Ringer's solution, ethyl alcohol, etc., and combinations thereof. Representative lubricating agents include magnesium stearate, calcium stearate, stearic acid, silica, talc, malt, glyceryl behanate, hydrogenated vegetable oils, polyethylene glycol, sodium benzoate, sodium acetate, sodium chloride, leucine, magnesium lauryl sulfate, sodium lauryl sulfate, etc., and combinations thereof. Representative natural oils include almond, apricot kernel, avocado, babassu, bergamot, black current seed, borage, cade, chamomile, canola, caraway, carnauba, castor, cinnamon, cocoa butter, coconut, cod liver, coffee, corn, cotton seed, emu, eucalyptus, evening primrose, fish, flaxseed, geraniol, gourd, grape seed, hazel nut, hyssop, isopropyl myristate, jojoba, kukui nut, lavandin, lavender, lemon, litsea cubeba, macademia nut, mallow, mango seed, meadowfoam seed, mink, nutmeg, olive, orange, orange roughy, palm, palm kernel, peach kernel, peanut, poppy seed, pumpkin seed, rapeseed, rice bran, rosemary, safflower, sandalwood, sasquana, savoury, sea buckthorn, sesame, shea butter, silicone, soybean, sunflower, tea tree, thistle, tsubaki, vetiver, walnut, and wheat germ oils. Representative synthetic oils include, but are not limited to, butyl stearate, caprylic triglyceride, capric triglyceride, cyclomethicone, diethyl sebacate, dimethicone 360, isopropyl myristate, mineral oil, octyldodecanol, oleyl alcohol, silicone oil, and combinations thereof. Attorney Docket No.103361-644WO1 Additionally, the composition may further comprise a polymer. Representative polymers contemplated herein include, but are not limited to, cellulosic polymers and copolymers, for example, cellulose ethers such as methylcellulose (MC), hydroxyethylcellulose (HEC), hydroxypropyl cellulose (HPC), hydroxypropyl methyl cellulose (HPMC), methylhydroxyethylcellulose (MHEC), methylhydroxypropylcellulose (MHPC), carboxymethyl cellulose (CMC) and its various salts, including, e.g., the sodium salt, hydroxyethylcarboxymethylcellulose (HECMC) and its various salts, carboxymethylhydroxyethylcellulose (CMHEC) and its various salts, other polysaccharides and polysaccharide derivatives such as starch, dextran, dextran derivatives, chitosan, and alginic acid and its various salts, carageenan, varoius gums, including xanthan gum, guar gum, gum arabic, gum karaya, gum ghatti, konjac and gum tragacanth, glycosaminoglycans and proteoglycans such as hyaluronic acid and its salts, proteins such as gelatin, collagen, albumin, and fibrin, other polymers, for example, polyhydroxyacids such as polylactide, polyglycolide, polyl(lactide-co-glycolide) and poly(.epsilon.-caprolactone-co-glycolide)-, carboxyvinyl polymers and their salts (e.g., carbomer), polyvinylpyrrolidone (PVP), polyacrylic acid and its salts, polyacrylamide, polyacrylic acid / acrylamide copolymer, polyalkylene oxides such as polyethylene oxide, polypropylene oxide, poly(ethylene oxide- propylene oxide), and a Pluronic polymer, polyoxy ethylene (polyethylene glycol), polyanhydrides, polyvinylalchol, polyethyleneamine and polypyrridine, polyethylene glycol (PEG) polymers, such as PEGylated lipids (e.g., PEG-stearate, l,2-Distearoyl-sn-glycero-3-Phosphoethanolamine-N- [Methoxy(Polyethylene glycol)-1000], 1,2-Distearoyl-sn-glycero-3-Phosphoethanolamine-N- [Methoxy(Polyethylene glycol)-2000], and 1,2-Distearoyl-sn-glycero-3- Phosphoethanolamine-N-[Methoxy(Polyethylene glycol)-5000]), copolymers and salts thereof. Additionally, the composition may further comprise an emulsifying agent. Representative emulsifying agents include, but are not limited to, a polyethylene glycol (PEG), a polypropylene glycol, a polyvinyl alcohol, a poly-N-vinyl pyrrolidone and copolymers thereof, poloxamer nonionic surfactants, neutral water-soluble polysaccharides (e.g., dextran, Ficoll, celluloses), non-cationic poly(meth)acrylates, non-cationic polyacrylates, such as poly (meth) acrylic acid, and esters amide and hydroxy alkyl amides thereof, natural emulsifiers (e.g. acacia, agar, alginic acid, sodium alginate, tragacanth, chondrux, cholesterol, xanthan, pectin, gelatin, egg yolk, casein, wool fat, cholesterol, wax, and lecithin), colloidal clays (e.g. bentonite [aluminum silicate] and Veegum [magnesium aluminum silicate]), long chain amino acid Attorney Docket No.103361-644WO1 derivatives, high molecular weight alcohols (e.g. stearyl alcohol, cetyl alcohol, oleyl alcohol, triacetin monostearate, ethylene glycol distearate, glyceryl monostearate, and propylene glycol monostearate, polyvinyl alcohol), carbomers (e.g. carboxy polymethylene, polyacrylic acid, acrylic acid polymer, and carboxy vinyl polymer), carrageenan, cellulosic derivatives (e.g. carboxymethylcellulose sodium, powdered cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose), sorbitan fatty acid esters (e.g. polyoxyethylene sorbitan monolaurate [Tween 20], polyoxyethylene sorbitan [Tween 60], polyoxyethylene sorbitan monooleate [Tween 80], sorbitan monopalmitate [Span 40], sorbitan monostearate [Span 60], sorbitan tristearate [Span 65], glyceryl monooleate, sorbitan monooleate [Span 80]), polyoxyethylene esters (e.g. polyoxyethylene monostearate [Myrj 45], polyoxyethylene hydrogenated castor oil, polyethoxylated castor oil, polyoxymethylene stearate, and Solutol), sucrose fatty acid esters, polyethylene glycol fatty acid esters (e.g. Cremophor), polyoxyethylene ethers, (e.g. polyoxyethylene lauryl ether [Brij 30]), poly(vinyl- pyrrolidone), diethylene glycol monolaurate, triethanolamine oleate, sodium oleate, potassium oleate, ethyl oleate, oleic acid, ethyl laurate, sodium lauryl sulfate, Pluronic F 68, Poloxamer 188, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, docusate sodium, etc. and / or combinations thereof. In certain aspects, the emulsifying agent is cholesterol. Liquid compositions include emulsions, microemulsions, solutions, suspensions, syrups, and elixirs. In addition to the active compound, the liquid composition may contain inert diluents commonly used in the art such as, for example, water or other solvents, solubilizing agents and emulsifiers such as ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils (in particular, cottonseed, groundnut, corn, germ, olive, castor, and sesame oils), glycerol, tetrahydrofurfuryl alcohol, polyethylene glycols and fatty acid esters of sorbitan, and mixtures thereof. Besides inert diluents, the oral compositions can also include adjuvants such as wetting agents, emulsifying and suspending agents, sweetening, flavoring, and perfuming agents. Injectable compositions, for example, injectable aqueous or oleaginous suspensions may be formulated according to the known art using suitable dispersing or wetting agents and suspending agents. The sterile injectable preparation may also be an injectable solution, suspension, or emulsion in a nontoxic parenterally acceptable diluent or solvent, for example, as a solution in 1,3-butanediol. Among the acceptable vehicles and solvents for pharmaceutical or cosmetic compositions that may be employed are water, Ringer's solution, U.S.P., and Attorney Docket No.103361-644WO1 isotonic sodium chloride solution. In addition, sterile, fixed oils are conventionally employed as a solvent or suspending medium. Any bland fixed oil can be employed including synthetic mono- or diglycerides. In addition, fatty acids such as oleic acid are used in the preparation of injectables. In certain aspects, the particles are suspended in a carrier fluid comprising 1% (w / v) sodium carboxymethyl cellulose and 0.1% (v / v) Tween 80. The injectable composition can be sterilized, for example, by filtration through a bacteria-retaining filter or by incorporating sterilizing agents in the form of sterile solid compositions, which can be dissolved or dispersed in sterile water or other sterile injectable medium prior to use. Compositions for rectal or vaginal administration may be in the form of suppositories which can be prepared by mixing the particles with suitable non-irritating excipients or carriers such as cocoa butter, polyethylene glycol, or a suppository wax which are solid at ambient temperature but liquid at body temperature and therefore melt in the rectum or vaginal cavity and release the particles. Solid compositions include capsules, tablets, pills, powders, and granules. In such solid compositions, the particles are mixed with at least one excipient and / or a) fillers or extenders such as starches, lactose, sucrose, glucose, mannitol, and silicic acid, b) binders such as, for example, carboxymethylcellulose, alginates, gelatin, polyvinylpyrrolidinone, sucrose, and acacia, c) humectants such as glycerol, d) disintegrating agents such as agar- agar, calcium carbonate, potato or tapioca starch, alginic acid, certain silicates, and sodium carbonate, e) solution retarding agents such as paraffin, f) absorption accelerators such as quaternary ammonium compounds, g) wetting agents such as for example, cetyl alcohol and glycerol monostearate, h) absorbents such as kaolin and bentonite clay, and i) lubricants such as talc, calcium stearate, magnesium stearate, solid polyethylene glycols, sodium lauryl sulfate, and mixtures thereof. In the case of capsules, tablets, and pills, the dosage form may also comprise buffering agents. Solid compositions of a similar type may also be employed as fillers in soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. Tablets, capsules, pills, and granules can be prepared with coatings and shells such as enteric coatings and other coatings well known in the pharmaceutical formulating art. They may optionally contain opacifying agents and can also be of a composition that they release the active ingredient(s) only, or preferentially, in a certain part of the intestinal tract, optionally, in a delayed manner. Examples of embedding compositions that can be used include polymeric substances and waxes. Solid compositions of a similar type may also be employed as fillers in Attorney Docket No.103361-644WO1 soft and hard-filled gelatin capsules using such excipients as lactose or milk sugar as well as high molecular weight polyethylene glycols and the like. Compositions for topical or transdermal administration include ointments, pastes, creams, lotions, gels, powders, solutions, sprays, inhalants, or patches. The active compound is admixed with an excipient and any needed preservatives or buffers as may be required. The ointments, pastes, creams, and gels may contain, in addition to the active compound, excipients such as animal and vegetable fats, oils, waxes, paraffins, starch, tragacanth, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc, and zinc oxide, or mixtures thereof. Powders and sprays can contain, in addition to the active compound, excipients such as lactose, talc, silicic acid, aluminum hydroxide, calcium silicates, polyamide powder, or mixtures of these substances. Sprays can additionally contain customary propellants such as chlorofluorohydrocarbons. Transdermal patches have the added advantage of providing controlled delivery of a compound to the body. Such dosage forms can be made by dissolving or dispensing the nanoparticles in a proper medium. Absorption enhancers can also be used to increase the flux of the compound across the skin. The rate can be controlled by either providing a rate-controlling membrane or by dispersing the particles in a polymer matrix or gel. Combinations In another aspect, the compounds disclosed herein can be administered in combination or alternation with one or more additional therapeutic agents. In some aspects, the compounds may be administered in combination with one or more additional therapeutic agents in the same pharmaceutical composition or may be administered as separate dosage forms. The term “therapeutic agent” includes any synthetic or naturally occurring biologically active compound or composition of matter which, when administered to an organism (either human or a nonhuman animal), induces a desired pharmacologic, immunogenic, and / or physiologic effect by local and / or systemic action. The term, therefore, encompasses those compounds or chemicals traditionally regarded as drugs, vaccines, and biopharmaceuticals, including molecules such as proteins, peptides, hormones, nucleic acids, gene constructs, and the like. Examples of therapeutic agents are described in well-known literature references such as the Merk Index (14thEdition), the Physician’s Desk Reference (64thEdition), and The Attorney Docket No.103361-644WO1 Pharmacological Basis of Therapeutics (12thEdition), and they include, without limitation, medicaments; vitamins; mineral supplements, substances used for the treatment, prevention, diagnosis, cure or mitigation of a disease or illness; substances that affect the structure or function of the body, or pro-drugs, which become biologically active or more active after they have been placed in a physiological environment. For example, the term “therapeutic agent” includes compounds or compositions for use in all of the major therapeutic areas including, but not limited to, adjuvants; anti-infectives such as antibiotics and antiviral agents; analgesics and analgesic combinations, anorexics, anti-inflammatory agents, anti-epileptics, local and general anesthetics, hypnotics, sedatives, antipsychotic agents, neuroleptic agents, antidepressants, anxiolytics, antagonists, neuron blocking agents, anticholinergic and cholinomimetic agents, antimuscarinic and muscarinic agents, antiandrenergics, antiarrhythmics, antihypertensive agents, hormones, and nutrients, antiarthritics, antiasthmatic agents, anticonvulsants, antihistamines, antinauseants, antineoplastics, antipruritics, antipyretics, antispasmodics, cardiovascular preparations (including calcium channel blockers, beta blockers, and beta- agonists), antihypertensives, diuretics, vasodilators, central nervous system stimulants, cough and cold preparations, decongestants, diagnostics, bone growth stimulants and bone resorption inhibitors, immunosuppressives, muscle relaxants, psychostimulants, sedatives, tranquilizers, proteins, peptides, and fragments thereof (whether naturally occurring, chemically synthesized or recombinantly produced), and nucleic acid molecules (polymeric forms of two or more nucleotides, either ribonucleotides (RNA) or deoxyribonucleotides (DNA) including both double and single-stranded molecules, gene constructs, expression vectors, antisense molecules and the like), small molecules and other biologically active macromolecules such as, for examples, proteins and enzymes. The agent may be a biologically active agent used in medical, including veterinary, applications and in agriculture, such as with plants, as well as other areas. In some aspects, the disclosed compounds can be administered in combination with one or more additional antimicrobial agents. For example, the disclosed compounds can be combined with one or more of Acedapsone; Acetosulfone Sodium; Alamecin; Alexidine; Amdinocillin; Amdinocillin Pivoxil; Amicycline; Amifloxacin; Amifloxacin Mesylate; Amikacin; Amikacin Sulfate; Aminosalicylic acid; Aminosalicylate sodium; Amoxicillin; Amphomycin; Ampicillin; Ampicillin Sodium; Apalcillin Sodium; Apramycin; Aspartocin; Astromicin Sulfate; Avilamycin; Avoparcin; Azithromycin; Azlocillin; Azlocillin Sodium; Bacampicillin Hydrochloride; Bacitracin; Bacitracin Methylene Disalicylate; Bacitracin Zinc; Bambermycins; Benzoylpas Calcium; Berythromycin; Betamicin Sulfate; Biapenem; Attorney Docket No.103361-644WO1 Biniramycin; Biphenamine Hydrochloride; Bispyrithione Magsulfex; Butikacin; Butirosin Sulfate; Capreomycin Sulfate; Carbadox; Carbenicillin Disodium; Carbenicillin Indanyl Sodium; Carbenicillin Phenyl Sodium; Carbenicillin Potassium; Carumonam Sodium; Cefaclor; Cefadroxil; Cefamandole; Cefamandole Nafate; Cefamandole Sodium; Cefaparole; Cefatrizine; Cefazaflur Sodium; Cefazolin; Cefazolin Sodium; Cefbuperazone; Cefdinir; Cefepime; Cefepime Hydrochloride; Cefetecol; Cefixime; Cefmenoxime Hydrochloride; Cefmetazole; Cefmetazole Sodium; Cefonicid Monosodium; Cefonicid Sodium; Cefoperazone Sodium; Ceforanide; Cefotaxime Sodium; Cefotetan; Cefotetan Disodium; Cefotiam Hydrochloride; Cefoxitin; Cefoxitin Sodium; Cefpimizole; Cefpimizole Sodium; Cefpiramide; Cefpiramide Sodium; Cefpirome Sulfate; Cefpodoxime Proxetil; Cefprozil; Cefroxadine; Cefsulodin Sodium; Ceftazidime; Ceftibuten; Ceftizoxime Sodium; Ceftriaxone Sodium; Cefuroxime; Cefuroxime Axetil; Cefuroxime Pivoxetil; Cefuroxime Sodium; Cephacetrile Sodium; Cephalexin; Cephalexin Hydrochloride; Cephaloglycin; Cephaloridine; Cephalothin Sodium; Cephapirin Sodium; Cephradine; Cetocycline Hydrochloride; Cetophenicol; Chloramphenicol; Chloramphenicol Palmitate; Chloramphenicol Pantothenate Complex; Chloramphenicol Sodium Succinate; Chlorhexidine Phosphanilate; Chloroxylenol; Chlortetracycline Bisulfate; Chlortetracycline Hydrochloride; Cinoxacin; Ciprofloxacin; Ciprofloxacin Hydrochloride; Cirolemycin; Clarithromycin; Clinafloxacin Hydrochloride; Clindamycin; Clindamycin Hydrochloride; Clindamycin Palmitate Hydrochloride; Clindamycin Phosphate; Clofazimine; Cloxacillin Benzathine; Cloxacillin Sodium; Cloxyquin; Colistimethate Sodium; Colistin Sulfate; Coumermycin; Coumermycin Sodium; Cyclacillin; Cycloserine; Dalfopristin; Dapsone; Daptomycin; Demeclocycline; Demeclocycline Hydrochloride; Demecycline; Denofungin; Diaveridine; Dicloxacillin; Dicloxacillin Sodium; Dihydrostreptomycin Sulfate; Dipyrithione; Dirithromycin; Doxycycline; Doxycycline Calcium; Doxycycline Fosfatex; Doxycycline Hyclate; Droxacin Sodium; Enoxacin; Epicillin; Epitetracycline Hydrochloride; Erythromycin; Erythromycin Acistrate; Erythromycin Estolate; Erythromycin Ethylsuccinate; Erythromycin Gluceptate; Erythromycin Lactobionate; Erythromycin Propionate; Erythromycin Stearate; Ethambutol Hydrochloride; Ethionamide; Fleroxacin; Floxacillin; Fludalanine; Flumequine; Fosfomycin; Fosfomycin Tromethamine; Fumoxicillin; Furazolium Chloride; Furazolium Tartrate; Fusidate Sodium; Fusidic Acid; Gentamicin Sulfate; Gloximonam; Gramicidin; Haloprogin; Hetacillin; Hetacillin Potassium; Hexedine; Ibafloxacin; Imipenem; Isoconazole; Isepamicin; Isoniazid; Josamycin; Kanamycin Sulfate; Kitasamycin; Levofuraltadone; Levopropylcillin Potassium; Lexithromycin; Lincomycin; Lincomycin Hydrochloride; Lomefloxacin; Lomefloxacin Attorney Docket No.103361-644WO1 Hydrochloride; Lomefloxacin Mesylate; Loracarbef; Mafenide; Meclocycline; Meclocycline Sulfosalicylate; Megalomicin Potassium Phosphate; Mequidox; Meropenem; Methacycline; Methacycline Hydrochloride; Methenamine; Methenamine Hippurate; Methenamine Mandelate; Methicillin Sodium; Metioprim; Metronidazole Hydrochloride; Metronidazole Phosphate; Mezlocillin; Mezlocillin Sodium; Minocycline; Minocycline Hydrochloride; Mirincamycin Hydrochloride; Monensin; Monensin Sodiumr; Nafcillin Sodium; Nalidixate Sodium; Nalidixic Acid; Natainycin; Nebramycin; Neomycin Palmitate; Neomycin Sulfate; Neomycin Undecylenate; Netilmicin Sulfate; Neutramycin; Nifuiradene; Nifuraldezone; Nifuratel; Nifuratrone; Nifurdazil; Nifurimide; Nifiupirinol; Nifurquinazol; Nifurthiazole; Nitrocycline; Nitrofurantoin; Nitromide; Norfloxacin; Novobiocin Sodium; Ofloxacin; Onnetoprim; Oxacillin Sodium; Oximonam; Oximonam Sodium; Oxolinic Acid; Oxytetracycline; Oxytetracycline Calcium; Oxytetracycline Hydrochloride; Paldimycin; Parachlorophenol; Paulomycin; Pefloxacin; Pefloxacin Mesylate; Penamecillin; Penicillin G Benzathine; Penicillin G Potassium; Penicillin G Procaine; Penicillin G Sodium; Penicillin V; Penicillin V Benzathine; Penicillin V Hydrabamine; Penicillin V Potassium; Pentizidone Sodium; Phenyl Aminosalicylate; Piperacillin Sodium; Pirbenicillin Sodium; Piridicillin Sodium; Pirlimycin Hydrochloride; Pivampicillin Hydrochloride; Pivampicillin Pamoate; Pivampicillin Probenate; Polymyxin B Sulfate; Porfiromycin; Propikacin; Pyrazinamide; Pyrithione Zinc; Quindecamine Acetate; Quinupristin; Racephenicol; Ramoplanin; Ranimycin; Relomycin; Repromicin; Rifabutin; Rifametane; Rifamexil; Rifamide; Rifampin; Rifapentine; Rifaximin; Rolitetracycline; Rolitetracycline Nitrate; Rosaramicin; Rosaramicin Butyrate; Rosaramicin Propionate; Rosaramicin Sodium Phosphate; Rosaramicin Stearate; Rosoxacin; Roxarsone; Roxithromycin; Sancycline; Sanfetrinem Sodium; Sarmoxicillin; Sarpicillin; Scopafungin; Sisomicin; Sisomicin Sulfate; Sparfloxacin; Spectinomycin Hydrochloride; Spiramycin; Stallimycin Hydrochloride; Steffimycin; Streptomycin Sulfate; Streptonicozid; Sulfabenz; Sulfabenzamide; Sulfacetamide; Sulfacetamide Sodium; Sulfacytine; Sulfadiazine; Sulfadiazine Sodium; Sulfadoxine; Sulfalene; Sulfamerazine; Sulfameter; Sulfamethazine; Sulfamethizole; Sulfamethoxazole; Sulfamonomethoxine; Sulfamoxole; Sulfanilate Zinc; Sulfanitran; Sulfasalazine; Sulfasomizole; Sulfathiazole; Sulfazamet; Sulfisoxazole; Sulfisoxazole Acetyl; Sulfisboxazole Diolamine; Sulfomyxin; Sulopenem; Sultamricillin; Suncillin Sodium; Talampicillin Hydrochloride; Teicoplanin; Temafloxacin Hydrochloride; Temocillin; Tetracycline; Tetracycline Hydrochloride ; Tetracycline Phosphate Complex; Tetroxoprim; Thiamphenicol; Thiphencillin Potassium; Ticarcillin Cresyl Sodium; Ticarcillin Disodium; Ticarcillin Monosodium; Ticlatone; Attorney Docket No.103361-644WO1 Tiodonium Chloride; Tobramycin; Tobramycin Sulfate; Tosufloxacin; Trimethoprim; Trimethoprim Sulfate; Trisulfapyrimidines; Troleandomycin; Trospectomycin Sulfate; Tyrothricin; Vancomycin; Vancomycin Hydrochloride; Virginiamycin; or Zorbamycin. In some aspects, the disclosed compounds can be administered in combination with one or more foaming agents such as sodium laureth ether sulfate (SLES), sodium lauryl dodecyl sulfate (SDS), disodium laureth sulfosuccinate, ammonium lauryl sulfate (ALS), sodium pareth sulfate, and sodium coceth sulfate. If in the same pharmaceutical composition, foaming agents can be present from about 1% to about 70%, about 5% to about 50%, about 10 % to about 30%, or about 1% to about 5% by weight. In some aspects, the disclosed compounds can be administered in combination with one or more antibiotics. Examples of antibiotics include amikacin, gentamicin, kanamycin, neomycin, streptomycin, tobramycin, bacitracin, clindamycin, daptomycin, lincomycin, linezolid, metronidazole, polymyxin, rifaximin, vancomycin, penicillin, cephalosporin, cephazolin, cephalexin, erythromycin, azithromycin, ciprofloxacin, levofloxacin, sulfadiazine, minocycline, tetracycline, and rifampin. If in the same pharmaceutical composition, the proportion of antibiotics can be about 0.001% to about 10%, about 0.01% to about 5%, about 0.1 % to about 10%, or about 1% to about 5% by weight. In some aspects, the disclosed compounds administered in combination with one or more therapeutic agents selected from as acyclovir, cephradine, malphalen, procaine, ephedrine, adriamycin, dauno, mycin, plumbagin, atropine, quinine, digoxin, and quinidine, cephradine, cephalothin, cishydroxy-L-proline, melphalan, nicotinic acid, nitric oxide, nitroglycerin, chemodeoxycholic acid, chlorambucil, paclitaxel, sirolimus, 5-flurouracil, paclitaxel, mercaptoethanesulfonate, verapamil, or antifungal agents. If in the same pharmaceutical composition, the proportion of these additional agents can be about 0.001% to about 10%, about 0.01% to about 5%, about 0.1 % to about 10%, or about 1% to about 5% by weight. In some aspects, the disclosed compounds can be administered in combination with one or more anti-inflammatory agents. Examples of such agents include acetaminophen, aspirin, celecoxib, diclofenac, diflunisal, flurbiprofen, ibuprofen, indomethacin, ketoprofen, ketorolac, meclofenamate, meloxicam, methyl salicylate, nabumetone, naproxen, oxaprozin, piroxicam, sulindac, tolmetin, trolamine. If in the same pharmaceutical composition, the proportion of these anti-inflammatory agents can be present in the formulation at from about 1% to about 70%, about 5% to about 50%, about 10 % to about 30%, or about 1% to about 5% by weight. Attorney Docket No.103361-644WO1 Methods of Use The compounds disclosed herein can be used to treat infections and inhibit the growth of bacteria. In some aspects, disclosed are methods of treating an infection in a patient, comprising administering to the patient a therapeutically effective amount of any of the compounds disclosed herein. Representative infections that can be treated include, but are not limited to, Actinobacter, Actinomycetes, Bacilli, Bortedellen, Clostridia, Corynebacteria, Enterobacter, Enterococci, Helicobacter, Haemophilus, Klebsiella, Listeria, Mycobacteria, Neisseria, Shigella, Salmonella, Streptococci, Staphylococci, tuberculosis bacteria, and Yersinia. In some aspects, the disclosed compounds can be used to treat infections caused by resistant Gram-positive bacteria, such as Methicillin Resistant Staphylococcus aureus (MRSA). Despite newly launched drugs and others in clinical development, the CDC characterizes MRSA as a serious threat, its second-highest level of concern. These disclosed methods can involve administering a compound disclosed herein to the infected human or animal or the human or animal at risk of being infected. In some specific aspects, the infected individual has cystic fibrosis. In some aspects, the disclosed compounds can be used to treat infections caused by resistant Gram-negative pathogens such as P. aeruginosa. Infections caused by Gram-negative bacteria in general, and MDR P. aeruginosa in particular (Wagner, S., et al. J. Med. Chem.2016, 59, 5929), represent a key need in antibacterial drug discovery that is currently underrepresented by approaches in clinical development. The additional permeability barrier imposed by the outer membrane of Gram-negative organisms (Zgurskaya, H. I., et al. ACS Infect. Dis.2015, 1, 512), as well as other resistance mechanisms, such as robust multidrug efflux transporters, make the identification of potential new therapies particularly challenging. These disclosed methods can involve administering a compound disclosed herein to the infected human or animal or the human or animal at risk of being infected. In some aspects, the disclosed compounds can be used to treat infections by M. tuberculosis, M. avium, or M. abscessus. In some aspects, the disclosed compounds can be used to treat infections caused by Enterococcus faecium, Klebsiella pneumoniae, Acinetobacter baumannii, various Enterobacter, and Neisseria gonorrhoeae. Further examples include the following diseases include: tuberculosis; Pneumonia; Typhoid; Paratyphoid; Syphilis, Gastritis; Gastroenteritis; Ruhr; Pestilence; Enteritis; extraintestinal infections, peritonitis and appendicitis with E. coli Attorney Docket No.103361-644WO1 and intestinal infections with EHEC, EPEC, ETEC and EIEC; Cholera, Legionnaires' disease, whooping cough, brucellosis, Lyme disease, leptospirosis, typhus, trachoma, gonorrhea, meningitis, septicemia, leprosy etc. These methods can involve administering a compound disclosed herein to the infected human or animal or the human or animal at risk of being infected. In some aspects, disclosed herein are methods of treating an infection in a patient, comprising administering to the patient a therapeutically effective amount of any of the compounds disclosed herein. In these disclosed methods, one can treat humans with infections but also can treat livestock (horses, cows, pigs, sheep, goats, etc.), poultry, and companion animals (dogs, cats, rabbits, etc.). The compositions or organisms can be administered alone or in combination with other therapeutics or nutritional supplements. For example, the composition can be combined into a feed. The active ingredient may be administered in such amounts, time, and route deemed necessary in order to achieve the desired result. The exact amount of the active ingredient will vary from subject to subject, depending on the species, age, and general condition of the subject, the severity of the medical disorder, the particular active ingredient, its mode of administration, its mode of activity, and the like. The active ingredient, whether the active compound itself or the active compound in combination with an agent, is preferably formulated in dosage unit form for ease of administration and uniformity of dosage. It will be understood, however, that the total daily usage of the active ingredient will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular subject will depend upon a variety of factors, including the disorder being treated and the severity of the disorder; the activity of the active ingredient employed; the specific composition employed; the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific active ingredient employed; the duration of the treatment; drugs used in combination or coincidental with the specific active ingredient employed; and like factors well known in the medical arts. The active ingredient may be administered by any route. In some aspects, the active ingredient is administered via a variety of routes, including oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, subcutaneous, intraventricular, transdermal, interdermal, rectal, intravaginal, intraperitoneal, topical (as by powders, ointments, creams, and / or drops), Attorney Docket No.103361-644WO1 mucosal, nasal, bucal, enteral, sublingual; by intratracheal instillation, bronchial instillation, and / or inhalation; and / or as an oral spray, nasal spray, and / or aerosol. In general, the most appropriate route of administration will depend upon a variety of factors, including the nature of the active ingredient (e.g., its stability in the environment of the gastrointestinal tract), the condition of the subject (e.g., whether the subject is able to tolerate oral administration), etc. The exact amount of an active ingredient required to achieve a therapeutically or prophylactically effective amount will vary from subject to subject, depending on species, age, and general condition of a subject, severity of the side effects or disorder, identity of the particular compound(s), mode of administration, and the like. The amount to be administered to, for example, a child or an adolescent can be determined by a medical practitioner or person skilled in the art and can be lower or the same as that administered to an adult. Useful dosages of the active agents and pharmaceutical compositions disclosed herein can be determined by comparing their in vitro activity and in vivo activity in animal models. Methods for the extrapolation of effective dosages in mice and other animals to humans are known to the art. The dosage ranges for the administration of the compositions are those large enough to produce the desired effect in which the symptoms or disorder are affected. The dosage should not be so large as to cause adverse side effects, such as unwanted cross-reactions, anaphylactic reactions, and the like. Generally, the dosage will vary with the age, condition, sex, and extent of the disease in the patient and can be determined by one of skill in the art. The dosage can be adjusted by the individual physician in the event of any counterindications. Dosage can vary and can be administered in one or more dose administrations daily for one or several days. The disclosed compounds can be administered either sequentially or simultaneously in separate or combined pharmaceutical formulations. When one or more of the disclosed compounds are used in combination with a second therapeutic agent, the dose of each compound can be either the same or differ from that when the compound is used alone. Appropriate doses will be readily appreciated by those skilled in the art. The term “administration” and variants thereof (e.g., “administering” a compound) in reference to a compound of the disclosure means introducing the compound or a prodrug of the compound into the system of the animal in need of treatment. When a compound of the disclosure or prodrug thereof is provided in combination with one or more other active agents Attorney Docket No.103361-644WO1 (e.g., a cytotoxic agent, etc.), “administration” and its variants are each understood to include concurrent and sequential introduction of the compound or prodrug thereof and other agents. In vivo application of the disclosed compounds and compositions containing them can be accomplished by any suitable method and technique presently or prospectively known to those skilled in the art. For example, the disclosed compounds can be formulated in a physiologically- or pharmaceutically-acceptable form and administered by any suitable route known in the art, including, for example, oral, nasal, rectal, topical, and parenteral routes of administration. As used herein, the term parenteral includes subcutaneous, intradermal, intravenous, intramuscular, intraperitoneal, and intrasternal administration, such as by injection. Administration of the disclosed compounds or compositions can be a single administration or at continuous or distinct intervals as can be readily determined by a person skilled in the art. The compounds disclosed herein and compositions comprising them can also be administered utilizing liposome technology, slow-release capsules, implantable pumps, and biodegradable containers. These delivery methods can, advantageously, provide a uniform dosage over an extended period of time. The compounds can also be administered in their salt derivative forms or crystalline forms. The compounds disclosed herein can be formulated according to known methods for preparing pharmaceutically acceptable compositions. Formulations are described in detail in a number of sources which are well known and readily available to those skilled in the art. For example, Remington’s Pharmaceutical Science by E.W. Martin (1995) describes formulations that can be used in connection with the disclosed methods. In general, the compounds disclosed herein can be formulated such that an effective amount of the compound is combined with a suitable carrier in order to facilitate the effective administration of the compound. The compositions used can also be in a variety of forms. These include, for example, solid, semi-solid, and liquid dosage forms, such as tablets, pills, powders, liquid solutions or suspensions, suppositories, injectable and infusible solutions, and sprays. The preferred form depends on the intended mode of administration and therapeutic application. The compositions also preferably include conventional pharmaceutically-acceptable carriers and diluents, which are known to those skilled in the art. Examples of carriers or diluents for use with the compounds include ethanol, dimethyl sulfoxide, glycerol, alumina, starch, saline, and equivalent carriers and diluents. To provide for the administration of such dosages for the desired therapeutic treatment, compositions disclosed herein can advantageously comprise between about 0.1% and 99%, and Attorney Docket No.103361-644WO1 especially, 1 and 15% by weight of the total of one or more of the subject compounds based on the weight of the total composition including carrier or diluent. Formulations suitable for administration include, for example, aqueous sterile injection solutions, which can contain antioxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the intended recipient, and aqueous and nonaqueous sterile suspensions, which can include suspending agents and thickening agents. The formulations can be presented in unit-dose or multi-dose containers, for example, sealed ampoules and vials, and can be stored in a freeze-dried (lyophilized) condition requiring only the condition of the sterile liquid carrier, for example, water for injections, prior to use. Extemporaneous injection solutions and suspensions can be prepared from sterile powder, granules, tablets, etc. It should be understood that in addition to the ingredients particularly mentioned above, the compositions disclosed herein can include other conventional agents in the art, having regard to the type of formulation in question. Compounds disclosed herein and compositions comprising them can be delivered to a cell either through direct contact with the cell or via a carrier means. Carrier means for delivering compounds and compositions to cells are known in the art and include, for example, encapsulating the composition in a liposome moiety. Another means for delivery of compounds and compositions disclosed herein to a cell comprises attaching the compounds to a protein or nucleic acid that is targeted for delivery to the target cell. U.S. Patent No.6,960,648 and U.S. Application Publication Nos.20030032594 and 20020120100 disclose amino acid sequences that can be coupled to another composition and that allow the composition to be translocated across biological membranes. U.S. Application Publication No. 20020035243 also describes compositions for transporting biological moieties across cell membranes for intracellular delivery. Compounds can also be incorporated into polymers, examples of which include poly (D-L lactide-co-glycolide) polymer, poly[bis(p-carboxyphenoxy) propane:sebacic acid] in a 20:80 molar ratio (as used in GLIADEL); chondroitin; chitin; and chitosan. Additional Aspects In view of the described compounds, compositions, and methods, hereinbelow are described certain more particular aspects of the disclosure. These particularly recited aspects should not, however, be interpreted to have any limiting effect on any different claims containing different or more general teachings described herein or that the “particular” aspects are somehow limited Attorney Docket No.103361-644WO1 in some way other than the inherent meanings of the language and formulae literally used therein. Aspect 1. A compound of Formula I-A or Formula I-B: or a pharmaceutically acceptable salt thereof, wherein: the dashed line represents a bond that is present or absent, and when the bond is present, R1and R2can be cis or trans; A is a fused bicyclic aryl or bicyclic heteroaryl ring optionally substituted with one or more groups independently selected from Z; or A and R1are brought together with the carbon to which they are attached to form a tricyclic ring optionally substituted with one or more groups independently selected from Z; B is a five- to six-membered heteroaryl ring having 1, 2, or 3 ring heteroatoms selected from N, O, and S, wherein B is optionally substituted with one or more groups independently selected from Z; D is an C5-C15aryl or C5-C15heteroaryl ring optionally substituted with one or more groups independently selected from Z; R1and R2are independently selected from H, OH, Cl, F, Br, I, CN, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, oxo, and C1-C6alkyl or C1- C6 alkoxyl optionally substituted with one or more groups independently selected from Z; Attorney Docket No.103361-644WO1 each R3is independently selected from C1-C6 alkyl, C1-C6 cycloalkyl, C5-C15 aryl, C4-C15 heteroaryl, C3-C15 heterocycloalkyl, and C1-C15 heteroalkyl, any of which are optionally substituted with one or more groups independently selected from Z; R9is H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, or C1-C6 alkyl or C1-C6 alkoxyl optionally substituted with one or more groups independently selected from Z; Z is independently selected at each occurrence from halo, nitro, cyano, azido, oxo, C1-C6alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 8-membered monocyclic or bicyclic heterocycle, 6- to 10-membered monocyclic or bicyclic aryl, 5- to 10-membered monocyclic or bicyclic heteroaryl, RxO-, RxS-, (RxRyN)-, RxO-C(O)-, RxS-C(O)-, (RxRyN)- C(O)-, RxO-S(O)2-, (RxRyN)-S(O)2-, RzC(O)-O-, RzC(O)-(RxN)-, RzS(O)2-O-, RzS(O)2-(RxN)- , RzC(O)-, RzS(O)-, and RzS(O)2-; Rxand Ryare independently selected at each occurrence from hydrogen, C1-C6alkyl, C1- C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, (C3-C7cycloalkyl)-(C0-C3 alkyl)-, (4- to 6-membered heterocycle)-(C0-C3 alkyl)-, (5- to 10-membered monocyclic or bicyclic aryl)-(C0-C3 alkyl)-, (5- to 10-membered monocyclic or bicyclic heteroaryl)-(C0-C3alkyl)-; and Rzis independently selected at each occurrence from hydrogen, halo, C1-C6alkyl, C1- C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, 4- to 6-membered heterocycle, 5- to 10-membered monocyclic or bicyclic aryl, 5- to 10-membered monocyclic or bicyclic heteroaryl, -ORx, -SRx, and -NRxRy. Aspect 2. The compound of aspect 1, wherein B is a five-membered heteroaryl ring having 1, 2, or 3 ring heteroatoms selected from N, O, and S, wherein B is optionally substituted with one or more groups independently selected from Z. Aspect 3. The compound of aspect 1 or aspect 2, wherein B is selected from furanyl, pyrrolyl, pyrazolyl, oxazolyl, imidazolyl, isoxazolyl, and triazolyl is optionally substituted with one or more groups independently selected from Z. Aspect 4. The compound of any one of aspects 1-3, wherein R1and R2are independently selected from from H, F, CN, OH, and NH2. Aspect 5. The compound of any one of aspects 1-4, wherein R2is NH2. Aspect 6. The compound of any one of aspects 1-4, wherein R2is H or OH. Aspect 7. The compound of any one of aspects 1-6, wherein R1is H or OH. Attorney Docket No.103361-644WO1 Aspect 8. The compound of any one of aspects 1-7, wherein A is a fused bicyclic aryl or bicyclic heteroaryl ring having Formula II: II wherein each X is independently CH or N; and R4and R5are independently selected from from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6 alkyl or C1-C6alkoxyl optionally substituted with one or more groups independently selected from Z. Aspect 9. The compound of aspect 8, wherein R4is selected from H, Cl, F, Br, I, OH, and unsubstituted C1-C6 alkyl or C1-C6 alkoxyl. Aspect 10. The compound of aspect 8 or aspect 9, wherein R4is selected from H, Cl, F, OH, and methoxy. Aspect 11. The compound of any one of aspects 8-10, wherein R4is selected from F and methoxy. Aspect 12. The compound of any one of aspects 1-7, wherein A and R1are brought together with the carbon to which they are attached to form a group of Formula IX, X, XI, or XII Attorney Docket No.103361-644WO1 XI XII wherein each X is independently CH, N, or CR8; R4and R5are independently selected from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6 alkyl or C1-C6 alkoxyl optionally substituted with one or more groups independently selected from Z; each R8is independently Cl, F, CN, OH, OCH3, CH3, or NH2; and R9is H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, or C1-C6 alkyl or C1-C6 alkoxyl optionally substituted with one or more groups independently selected from Z. Aspect 13. The compound of aspect 12, wherein R4is H and R5is F. Aspect 14. The compound of any one of aspects 1-13, wherein D is selected from Formula IV-VIII or XIII: Attorney Docket No.103361-644WO1 VIII XIII wherein each X is independently selected from CH or N; each Y is independently selected from O, S, NH, or CH2; and R6and R7are independently selected from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6 alkyl or C1-C6 alkoxyl optionally substituted with one or more groups independently selected from Z. Aspect 15. The compound of aspect 14, wherein R6and R7are independently selected from H, Cl, F, Br, I, CN, OH, and unsubstituted C1-C6 alkyl or C1-C6 alkoxyl. Aspect 16. The compound of aspect 14, wherein R6and R7are independently selected from H, Cl, F, CN, OH, and methoxy. Aspect 17. The compound of aspect 14, wherein R6and R7are both H. Aspect 18. The compound any one of aspects 14-17, wherein each Y is O. Aspect 19. The compound of any one of aspects 14-17, wherein one Y is S and the other is O. Aspect 20. The compound of any one of aspects 14-17, wherein one Y is NH and the other is O. Attorney Docket No.103361-644WO1 Aspect 21. The compound of any one of aspects 14-17, wherein one Y is NH and the other is S. Aspect 22. The compound of any one of aspects 1-21, wherein the dashed line is a bond that is present. Aspect 23. The compound of any one of aspects 1-21, wherein the dashed line is a bond that absent. Aspect 24. The compound of aspect 1, wherein the compound is selected from: 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)furan-2-yl)piperidin-1-yl)ethyl)-1,5-naphthyridine (example 1); 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)furan-2-yl)piperidin-1-yl)ethyl)-7-fluoro-2- methoxy-1,5-naphthyridine (example 2); 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)furan-2-yl)-2H- benzo[b][1,4]oxazin-3(4H)-one (example 3); 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-pyrrol-2-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 4); 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrrol-2-yl)piperidin-1-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 5); 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-pyrrol-2-yl)- 2H-benzo[b][1,4]oxazin-3(4H)-one (example 6); 5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-2-(p-tolyl)oxazole (example 7); 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)ethyl)piperidin-4-yl)oxazole (example 8); 3-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-5-(p-tolyl)isoxazole (example 9); 5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)ethyl)piperidin-4-yl)isoxazole (example 10); 6-(3-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)isoxazol-5-yl)- 2H-benzo[b][1,4]oxazin-3(4H)-one (example 11); Attorney Docket No.103361-644WO1 5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-3-(p-tolyl)isoxazole (example 12); 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)ethyl)piperidin-4-yl)isoxazole (example 13); 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)isoxazol-3-yl)- 2H-benzo[b][1,4]oxazin-3(4H)-one (example 14); 7-fluoro-2-methoxy-8-(2-(4-(1-(p-tolyl)-1H-1,2,3-triazol-4-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 15); 8-(2-(4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-4-yl)piperidin-1-yl)ethyl)- 7-fluoro-2-methoxy-1,5-naphthyridine (example 16); 7-fluoro-2-methoxy-8-(2-(4-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 17); 8-(2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)ethyl)- 7-fluoro-2-methoxy-1,5-naphthyridine (example 18); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 19); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (example 20); 8-(2-(4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)ethyl)-7-fluoro-2- methoxy-1,5-naphthyridine (example 21); 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 22); 7-fluoro-2-methoxy-8-(2-(4-(4-(p-tolyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 23); 8-(2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-1-yl)piperidin-1-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 24); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-pyrazol-4- yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 25); Attorney Docket No.103361-644WO1 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-(4-(4-(p-tolyl)-1H-1,2,3-triazol-1- yl)piperidin-1-yl)ethan-1-ol (example 26); 2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)-1-(3- fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol (example 27); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl)piperidin-4-yl)-1H- 1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 28); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl)piperidin-4-yl)-1H- 1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (example 29); 2-(4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)-1-(3-fluoro-6-methoxy- 1,5-naphthyridin-4-yl)ethan-1-ol (example 30); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 4-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (example 31); 7-fluoro-2-methoxy-8-(2-((2r,5r)-5-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2-yl)ethyl)- 1,5-naphthyridine (example 32); 8-(2-((2r,5r)-5-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2- yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine (example 33); 6-(1-((2r,5r)-2-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)-1,3-dioxan-5-yl)-1H- 1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 34); 8-(2-((2r,5r)-5-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 35); (S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-((2r,5S)-5-(4-(p-tolyl)-1H-1,2,3-triazol- 1-yl)-1,3-dioxan-2-yl)ethan-1-ol (example 36); (S)-1-((2r,5S)-5-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan- 2-yl)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol (example 37); 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-hydroxyethyl)-1,3- dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 38); 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-hydroxyethyl)-1,3- dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (example 39); Attorney Docket No.103361-644WO1 (S)-1-((2r,5S)-5-(4-(5,6-dichloropyrazin-2-yl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2-yl)-2-(3- fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol (example 40); 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-hydroxyethyl)-1,3- dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (example 41); 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-pyrazol-3-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 42); 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-3-yl)piperidin-1-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 43); 7-fluoro-2-methoxy-8-(2-(4-(1-methyl-5-(p-tolyl)-1H-pyrazol-3-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 44, first regioisomer); 7-fluoro-2-methoxy-8-(2-(4-(1-methyl-3-(p-tolyl)-1H-pyrazol-5-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 44, second regioisomer); 6-(4-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 45); and 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl)piperidin-4-yl)-1H- 1,2,3-triazol-4-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (example 46); or a pharmaceutically acceptable salt thereof. Aspect 25. The compound of any one of aspects 1-24, wherein the compound is a type II topoisomerase inhibitor. Aspect 26. A pharmaceutical composition comprising a compound of any one of aspects 1- 25, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient. Aspect 27. A method of treating an infection in a subject in need thereof comprising administering a compound of any one of aspects 1-25, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of aspect 26. Aspect 28. The method of aspect 27, wherein the infection is a Staphylococcus aureus infection. Aspect 29. The method of aspect 27, wherein the infection is a methicillin-resistant Staphylococcus aureus (MRSA) infection. Attorney Docket No.103361-644WO1 Aspect 30. The method of aspect 27, wherein the infection is an Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, or Salmonella enterica infection. A number of aspects of the disclosure have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the disclosure. Accordingly, other aspects are within the scope of the following claims. By way of non-limiting illustration, examples of certain aspects of the present disclosure are given below. EXAMPLES The following examples are set forth below to illustrate the compounds, compositions, and methods claimed herein, along with associated methods and results according to the disclosed subject matter. These examples are not intended to be inclusive of all aspects of the subject matter disclosed herein, but rather to illustrate representative methods and results. These examples are not intended to exclude equivalents and variations of the present disclosure, which are apparent to one skilled in the art. Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.), but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in °C or is at ambient temperature, and pressure is at or near atmospheric. There are numerous variations and combinations of reaction conditions, e.g., component concentrations, temperatures, pressures, and other reaction ranges and conditions that can be used to optimize the product purity and yield obtained from the described process. Only reasonable and routine experimentation will be required to optimize such process conditions. General Procedures 1. Titanium-mediated methyl ketone cross-coupling. Tert-butyl 4-(2- bromoacetyl)piperidine-1-carboxylate (1.2 eq), aryl methyl ketone (1 eq), and titanium isopropoxide (2 eq) were added to round bottom flask (RBF). Then this was heated to 80°C overnight. Upon return, reaction was cooled to room temperature and diluted with ethyl acetate. Then this was poured into a beaker containing 25 mL aqueous, saturated ammonium chloride and stirred with for an extra 5 minutes. Then reaction was filtered through a celite plug, washing with additional ethyl acetate. Organics were then separated from the aqueous layer. Then organics were dried over sodium sulfate and Attorney Docket No.103361-644WO1 concentrated by rotary evaporation to afford crude mixtures. Crude mixtures were purified by flash chromatography. Paal-Knorr furan synthesis / Boc- deprotection. Diketone starting material (1 eq) was dissolved in methanol (0.25 M). Then 4 M HCl in Dioxane (2.5 eq) was added to the reaction and allowed to stir, monitoring by TLC for consumption of starting material. Once starting material was consumed, reaction was concentrated to afford crude mixtures. Crude mixtures were used directly in the next step with no purification. Reductive amination. 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)acetaldehyde (1 eq) was added to RBF containing deprotected piperidine (1-1.5 eq). This was dissolved in methanol (0.2 M) and THF (0.2M). Then 4Å molecular sieves (150 mg / mmol aldehyde) were added, followed by acetic acid (1.5 eq). This was allowed to stir for 4 hours, then sodium cyanoborohydride (1.5-2 eq) was added. This stirred an additional hour, then reaction was quenched with aqueous sodium carbonate. Reaction was then extracted from 5 x 10 mL of 20% methanol in DCM. Organics were then dried over sodium sulfate and concentrated by rotary evaporation to afford crude mixtures. Crude mixtures were then purified by flash chromatography. Paal-Knorr pyrrole synthesis. Diketone starting material (1 eq) was added to RBF and dissolved in acetonitrile (0.1M). Then 7 M ammonia in methanol (5 eq) was added, followed by ammonium acetate (1 eq), and acetic acid (1 eq). This was then allowed to stir overnight at 65°C. Upon return, reaction was cooled to room temperature and diluted with ethyl acetate. Then reaction was further diluted with aqueous ammonium chloride. This was then filtered through a celite plug, washing with ethyl acetate. Then organics were separated from the aqueous layer and further dried using sodium sulfate. Then organics were concentrated by rotary evaporation to afford crude mixtures. Crude mixtures were then purified by flash chromatography. Boc- deprotection. Boc-protected piperidine (1 eq) was dissolved in methanol (0.25 M). Then 4 M HCl in Dioxane (2.5 eq) was added to the reaction and allowed to stir, monitoring by TLC for consumption of starting material. Once starting material was consumed, reaction was concentrated by rotary evaporation to afford crude mixtures. Crude mixtures were used directly in the next step with no purification. “Furan-like” Oxazole synthesis. Tert-butyl 4-(2-bromoacetyl)piperidine-1- carboxylate (1 eq), amine (1.2 eq), and potassium carbonate (4 eq) were added to RBF. Attorney Docket No.103361-644WO1 Compounds were dissolved in DMF (0.25 M) and then iodine (2.2 eq) was added. This was allowed to stir at 80°C overnight. Upon return, reaction was cooled to room temperature, diluted with ethyl acetate, and quenched with aqueous sodium thiosulfate. Then organics were separated from aqueous layer, and the aqueous layer was extracted from, using 5 x 15 mL ethyl acetate. Then organics were combined and concentrated by rotary evaporation to afford crude mixtures. Crude mixtures were then purified by flash chromatography. 7. Isoxazole synthesis. Aldehyde (1 eq) was dissolved in t-butanol (0.5 M) and then hydroxylamine hydrogen chloride (1.05 eq) was added to RBF. Then 1 M sodium hydroxide (1.05 eq) was added to RBF and allowed to stir for 30 minutes. Then chloramine T trihydrate (1.05 eq) was added and allowed to stir an additional 15 mins. Then copper sulfate (0.07 eq) and alkyne (1.05 eq) were added to RBF. pH was then adjusted to ~6 using 0.1 M sodium hydroxide. This was then allowed to stir overnight. Upon return, reaction was quenched with aqueous ammonium chloride and filtered through a celite plug, washing with ethyl acetate. Then organics were separated from the aqueous layer and further dried with sodium sulfate. Then organics were concentrated by rotary evaporation to afford crude mixtures. Crude mixtures were then purified by flash chromatography. 8. Reverse triazole “Click” chemistry. Boronic acid (1 eq), sodium azide (1.2 eq), and copper sulfate (0.2 eq) were added to RBF and dissolved in methanol (0.25 M). This was heated to 40°C and allowed to stir, monitoring by TLC for consumption of starting material. Once starting material was consumed, reaction was cooled to room temperature, then tert-butyl 4-ethynylpiperidine-1-carboxylate (1.5 eq) and sodium ascorbate (0.4 eq) were added to reaction. This was allowed to stir overnight at room temperature. Upon return, reaction was diluted with water and filtered through celite plug. The celite plug was washed with ethyl acetate, and the organics were separated from the aqueous layer. Then ethyl acetate was dried over sodium sulfate and concentrated by rotary evaporation to afford crude compounds. Compounds could be purified by flash chromatography. 9. Sonogashira reaction. Bromo- starting material (1 eq), THF (0.463 M), trimethylsilyl acetylene (5 eq), and tetramethyl ethylenediamine (14 eq) were all added to a round bottom flask in order. Then solution was degassed with 1x nitrogen balloon. Then copper iodide (0.15 eq) and tetrakis (triphenylphosphine)palladium (0.05 eq) were Attorney Docket No.103361-644WO1 added to the reaction solution. The reaction was then heated to 60°C and allowed to stir overnight under a nitrogen atmosphere. Upon return, reaction was cooled to room temperature and diluted with ethyl acetate and water. The ethyl acetate was separated, and the water layer was extracted from 5x15 mL ethyl acetate. Then organics were combined and dried over sodium sulfate. Then organics were concentrated by rotary evaporation and purified by flash chromatography. TMS-deprotection. TMS-protected starting material (1 eq), potassium carbonate (2 eq), and methanol (0.244M) were all added to a round bottom flask. This was allowed to stir for 1-4 hours, monitoring for the disappearance of starting material by TLC. Once starting material was consumed, the reaction was filtered through a celite plug, washing with excess methanol. Then organics were concentrated by rotary evaporation. Compound could be purified by flash chromatography, if necessary. Triazole multi-step synthesis. Tert-butyl 4-iodopiperidine-1-carboxylate (1 eq) and sodium azide (1.05 eq) were added to RBF, followed by DMF (0.2 M). This was allowed to stir overnight. Upon return, reaction was diluted with water and extracted 5 x 15 mL ethyl acetate. Then organics were separated, dried over sodium sulfate, and concentrated by rotary evaporation to afford crude azide. This was then dissolved in DMF (0.2 M), then alkyne (1 eq), copper iodide (0.1 eq), and triethylamine (0.4 eq) were added to reaction and allowed to stir overnight. Upon return, reaction was diluted with water and filtered through a Büchner funnel. The filter flask was then changed for a new flask, and the precipitate was flushed through the Büchner using excess ethyl acetate. Then ethyl acetate was dried over sodium sulfate and concentrated to afford crude triazoles. This was then dissolved in methanol (0.2 M) and 4 M HCl in dioxane (2.5 eq) was added to reaction. This was allowed to stir, monitoring for consumption of starting material by TLC. Once starting material was gone, reaction was diluted with methanol and quenched, slowly, with aqueous sodium carbonate. Then reaction was further diluted with DCM, and organics were separated from the aqueous layer. Aqueous layer was further extracted with 5 x 10% methanol in DCM. Organics were collected, dried over sodium sulfate, and concentrated by rotary evaporation to afford crude mixtures. Crude mixtures were purified by flash chromatography. Imidazole synthesis. Tert-butyl 4-formylpiperidine-1-carboxylate (1 eq) was added to RBF and dissolved in t-butanol (0.1 M). DABCO (0.07 eq) was added to reaction and allowed to stir for 15 mins. Then 2-oxo-2-(p-tolyl)acetaldehyde (1 eq) was added Attorney Docket No.103361-644WO1 followed by ammonium acetate (2 eq). This was heated to 65°C and allowed to stir overnight. Upon return, reaction was cooled to room temperature and concentrated by rotary evaporation to afford crude mixture. Crude mixture was purified by flash chromatography. 13. Suzuki reaction. Tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H- pyrazol-1-yl)piperidine-1-carboxylate (1.2 eq), potassium carbonate (2 eq), Pd(dppf)Cl2(0.05 eq), and aryl-bromide (1 eq) were added to RBF. The RBF was purged with nitrogen three times. Then dioxane (0.2 M) and water (1 M) were added to RBF. Reaction was set to stir and heated to 100°C overnight, under a nitrogen atmosphere. Upon return, reaction was cooled to room temperature and filtered through a celite plug, washing with ethyl acetate. Then ethyl acetate was washed with brine, dried over sodium sulfate, and concentrated by rotary evaporation to afford crude mixtures. Crude mixtures were purified by flash chromatography. 14. Vinylation reaction. 8-bromo-7-fluoro-2-methoxy-1,5-naphthyridine (1 eq), potassium vinyl trifluoroborate (1.5 eq), [1,1'- Bis(diphenylphosphino)ferrocene]palladium(II) dichloride (0.05 eq), triethylamine (2 eq), and isopropanol (0.0667M) were all added to a pressure vial. Reaction was heated to 100°C and allowed to stir overnight. Upon return, reaction was cooled to room temperature, and filtered through a celite plug washing with excess ethyl acetate. Then organics were concentrated by rotary evaporation. Then crude mixture was purified by flash chromatography. 15. Racemic Dihydroxylation. 8-ethenyl-7-fluoro-2-methoxy-1,5-naphthyridine (1 eq), potassium osmate (0.02 eq), N-methylmorpholine N-oxide (1.1eq), chloroform (0.33M), and water (1M) were added to a round bottom flask. Reaction was heated to 60°C and allowed to stir overnight. Upon return, reaction was cooled to room temperature and quenched with aqueous, saturated sodium sulfite. Reaction was then extracted from 5x15 mL ethyl acetate. Organics were dried over sodium sulfate and concentrated by rotary evaporation. Crude mixtures were purified by flash chromatography. 16. Epoxide formation. 1-(3-fluoro-6-methoxy-1,5-diaza-4-naphthyl)-1,2-ethanediol (1 eq), 1-pyridinium p-toluenesulfonate (0.1 eq), and DCM (0.163M) were added to a round bottom flask under a nitrogen atmosphere. Trimethyl orthoacetate was added and Attorney Docket No.103361-644WO1 allowed to stir for 1.5 hours. TMS-chloride (3 eq) was added and allowed to stir overnight. Upon return, reaction was concentrated by rotary evaporation. Then mixture was dissolved in methanol (0.114M) and potassium carbonate (5 eq) was added to the reaction. This was allowed to stir for 1 hour. Reaction was then quenched with saturated, aqueous ammonium chloride. Then reaction was diluted with water and DCM. DCM was separated, and water layer was extracted from 3x10 mL DCM. Organics were dried over sodium sulfate and concentrated by rotary evaporation to afford crude mixture. This was purified by flash chromatography. Nucleophilic epoxide opening. 7-fluoro-2-methoxy-8-(2-oxiranyl)-1,5- diazanaphthalene (1 eq), deprotected piperidine (2 eq), and ethanol (0.068M) were all added to a pressure vial. This was heated to 100°C and allowed to stir overnight. Upon return, reaction was cooled to room temperature, diluted with water, and extracted from 5x10 mL 10% methanol in DCM. Organics were dried over sodium sulfate and concentrated by rotary evaporation. Crude mixtures were purified by flash chromatography. Azide substitution. 7-fluoro-8-[2-(4-iodopiperidin-1-yl)ethyl]-2-methoxy-1,5- naphthyridine (1 eq), sodium azide (1.5 eq), and DMF (0.111M) were all added to a round bottom flask. This was allowed to stir overnight. Upon return, reaction was diluted with water and extracted from 5x10 mL ethyl acetate. Organics were dried over sodium sulfate and concentrated by rotary evaporation. “Click” Chemistry. Method A.8-[2-(4-azido-1-piperidyl)ethyl]-7-fluoro-2-methoxy- 1,5-diazanaphthalene (1 eq), alkyne (2 eq), triethylamine (0.1 eq), copper iodide (0.1 eq), and DMF (0.1M) were all added to a round bottom flask and allowed to stir overnight. Upon return, reaction was diluted with water and filtered through a Büchner funnel. Precipitate was collected after drying. Product could be purified by flash chromatography, if necessary. Method B. Azide (1 eq), alkyne (1 eq), aqueous solution of sodium ascorbate (0.5 eq in 0.5M water), and aqueous solution of copper sulfate (0.15 eq in 0.5M water) were all added to a round bottom flask in order. Reaction was allowed to stir until starting material was consumed, monitoring by TLC. Once starting material was consumed, reaction was cooled to 0°C to form a precipitate. The precipitate was collected by Attorney Docket No.103361-644WO1 filtration through a Büchner funnel, washing with ethyl acetate and DCM. Precipitate could be purified by flash chromatography if necessary. 20. Azido transfer. Amine (1.02 eq), organic solution of (fluorosulfonyl)-1,2-triazadien-2- ium-1-ide (1 eq), and an aqueous solution of potassium bicarbonate (3M) were added to a round bottom flask in order. Reaction stirred, monitoring by TLC for consumption of starting material. Once starting material was consumed, reaction was diluted with ethyl acetate and washed 5x10 mL brine, 2x5 mL water, and 1x10 mL brine. Organics were dried over sodium sulfate and concentrated by rotary evaporation. Crude mixture was purified by flash chromatography. 21. Aldol Condensation. Quinuclidin-3-one (1 eq) and sodium hydroxide (0.2 eq) were added to a round bottom flask. Ethanol (1.1 M) was added, and the reaction was heated to 50°C for 1 hour. Then aldehyde (1.2 eq) was added to reaction and heated to 80°C for 3 hours. After 3 hours, reaction was cooled to room temperature and quenched with water. Reaction was extracted 5x10 mL DCM. DCM was dried over sodium sulfate, then concentrated by rotary evaporation. Crude mixture was purified by flash chromatography. 22. Pyrazole Formation. Quinuclidinone starting material (1 eq), potassium hydroxide (1.7 eq), 4 Å molecular sieves (1g / mmol starting material), and ethylene glycol (1.5 M) were added to a pressure tube. Then hydrazine (1.5 eq) was added. This was capped and placed in a Monowave reactor. This was heated to 115°C for 15 mins, then heat to 190°C over 15 mins, followed by holding 190°C for 3 hours. Once completed, reaction was cooled to room temperature and allowed to settle to avoid opening tube with pressure. Once cool, the slurry was diluted with water and extracted 5x10 mL DCM. Then organics were dried over sodium sulfate and concentrated by rotary evaporation. Crude mixture was purified by flash chromatography. 23. Aldol Reaction. Anhydrous THF (0.5 M) was added to an oven-dried flask, followed by DIPA (2 eq). This was cooled to 0°C, then N-butyllithium (2 eq) was added dropwise to the flask. After addition, reaction was allowed to stir an additional 15 mins. In a separate flask, 1-tert-butoxycarbonyl-4-piperidinecarboxylic acid (1 eq) was dissolved in anhydrous THF (0.22 M) then CDI (1.1 eq) was added. This was allowed to stir for 45 mins. The prepped LDA was cooled to -78°C, and methyl ketone (2.3 eq, in anhydrous THF [2.22 M]) was added dropwise. Next, the solution containing piperidine Attorney Docket No.103361-644WO1 and CDI was added dropwise to LDA / ketone mixture. After addition reaction was allowed to stir an additional 45 mins. Then solution was warmed to room temperature, diluted with ethyl acetate, washed with 1 M citric acid, washed with aqueous sat. sodium bicarbonate and washed with brine. Organic layer was then dried over sodium sulfate and concentrated by rotary evaporation. Crude mixture was purified by flash chromatography. 24. Methyl-Pyrazole Formation. tert-butyl 4-[(Z)-3-hydroxy-3-(p-tolyl)acryloyl]-1- piperidinecarboxylate (1 eq), methylhydrazine (1.8 eq), methanol (0.153 M), and DMF (0.382 M) were added to a round bottom flask. This was allowed to stir overnight. Upon return, reaction was diluted with water and extracted 5x10 mL ethyl acetate. Then ethyl acetate was dried over sodium sulfate and concentrated by rotary evaporation. Crude mixture was purified by flash chromatography. Characterization tert-butyl 4-(4-oxo-4-(p-tolyl)butanoyl)piperidine-1-carboxylate (3a) Title compound was synthesized from tert-butyl 4-(2-bromoacetyl)piperidine-1-carboxylate and 1-(p-tolyl)ethan-1-one using General Procedure 1. Purification by flash chromatography (compound eluted in 15% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as an orange oil (100 mg, 0.278 mmol, 33% yield).1HNMR (CDCl3, 400 MHz, contaminated w / ethyl acetate, not pure) δ: 7.87 (d, J = 8.2 Hz, 2H), 7.27-7.24 (m, obscured by chloroform, 2H), 4.19-4.05 (m, 2H), 3.28 (t, J = 6.0 Hz, 2H), 2.87 (t, J = 6.2 Hz, 2H), 2.86- 2.75 (m, 2H), 2.62 (tt, J = 3.9, 11.6 Hz, 1H), 2.41 (s, 3H), 1.94-1.85 (m, 2H), 1.65-1.54 (m, obscured by water, 2H), 1.46 (s, 9H). Attorney Docket No.103361-644WO1 tert-butyl 4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-4-oxobutanoyl)piperidine-1- carboxylate (3b) Title compound was synthesized from tert-butyl 4-(2-bromoacetyl)piperidine-1-carboxylate and 1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)ethan-1-one using General Procedure 1. Purification by flash chromatography (compound eluted in 25% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as an orange oil (150 mg, 0.372 mmol, 45% yield).1HNMR (CDCl3, 400 MHz) δ: 7.53-7.49 (m, 2H), 6.90 (d, J = 9.0 Hz, 1H), 4.33-4.26 (m, 4H), 4.16-4.06 (m, 2H), 3.22 (t, J = 6.0 Hz, 2H), 2.85 (d, J = 6.2 Hz, 2H), 2.84-2.76 (m, 2H), 2.61 (tt, J = 3.6, 11.4 Hz, 1H), 1.93-1.85 (m, 2H), 1.64-1.55 (m, 2H, obscured by water), 1.45 (s, 9H). tert-butyl 4-(4-oxo-4-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6- yl)butanoyl)piperidine-1-carboxylate (3c) Title compound was synthesized from tert-butyl 4-(2-bromoacetyl)piperidine-1-carboxylate and 6-acetyl-2H-benzo[b][1,4]oxazin-3(4H)-one using General Procedure 1. Purification by flash chromatography (compound eluted in 40% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a yellow oil (30 mg, 0.072 mmol, 7% yield).1HNMR (CDCl3, 400 MHz, contaminated with ethyl acetate) δ: 8.16 (s, 1H), 7.65 (dd, J = 2.0, 8.4 Hz, 1H), 7.46 (d, J = 2.0 Hz, 1H), 7.02 (d, J = 8.4 Hz, 1H), 4.69 (s, 2H), 4.16-4.06 (m, 3H, obscured by ethyl acetate), 3.23 (t, J = 5.9 Hz, 2H), 2.89 (t, J = 6.1 Hz, 2H), 2.87-2.76 (m, 3H), 2.61 (tt, J = 3.7, 11.3 Hz, 1H), 1.93-1.85 (m, 2H), 1.45 (s, 9H). 4-(5-(p-tolyl)furan-2-yl)piperidine (4a) Attorney Docket No.103361-644WO1 Title compound was synthesized from tert-butyl 4-(4-oxo-4-(p-tolyl)butanoyl)piperidine-1- carboxylate using General Procedure 2. Concentration in vacuo afforded the title compound as an orange solid. No purification or isolation attempted. 4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)furan-2-yl)piperidine (4b) Title compound was synthesized from tert-butyl 4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)- 4-oxobutanoyl)piperidine-1-carboxylate using General Procedure 2. Concentration in vacuo afforded the title compound as a yellow solid. No purification or isolation attempted. 6-(5-(piperidin-4-yl)furan-2-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (4c) Title compound was synthesized from tert-butyl 4-(4-oxo-4-(3-oxo-3,4-dihydro-2H- benzo[b][1,4]oxazin-6-yl)butanoyl)piperidine-1-carboxylate using General Procedure 2. Concentration in vacuo afforded the title compound as an orange solid. No purification or isolation attempted. Example 1. 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)furan-2-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(5-(p-tolyl)furan-2-yl)piperidine using General Procedure 3. Attorney Docket No.103361-644WO1 Purification by flash chromatography (compound eluted in 50% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as a white solid (7 mg, 0.0157 mmol, 23% yield).1HNMR (CDCl3, 400 MHz, contaminated with DCM) δ: 8.65 (s, 1H), 8.20 (d, J = 9.0 Hz, 1H), 7.54 (d, J = 8.1 Hz, 2H), 7.19 (d, J = 7.9 Hz, 2H), 7.10 (d, J = 9.1 Hz, 1H), 6.51 (d, J = 3.2 Hz, 1H), 6.08 (d, J = 3.1 Hz, 1H), 4.13 (s, 3H), 3.50-3.43 (m, 2H), 3.22-3.15 (m, 2H), 2.84-2.78 (m, 2H), 2.78-2.69 (m, 1H), 2.38 (s, 3H), 2.34-2.26 (m, 2H), 2.13-2.05 (m, 2H), 1.89- 1.78 (m, 2H). HRMS (ESI) m / z calc’d for C27H28FN3O2[M+H]+: 446.22383; found: 446.22321. UPLC: rt: 4.06 min, purity: 95.94%. Example 2. 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)furan-2-yl)piperidin-1- yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)furan-2-yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 50% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (12 mg, 0.0245 mmol, 18% yield).1HNMR (CDCl3, 400 MHz, contaminated with ethyl acetate) δ: 8.62 (d, J = 0.4 Hz, 1H), 8.17 (d, J = 9.0 Hz, 1H), 7.14 (d, J = 2.0 Hz, 1H), 7.09 (d, J = 2.1, 8.4 Hz, 1H), 7.07 (d, J = 9.0 Hz, 1H), 6.84 (d, J = 8.4 Hz, 1H), 6.39 (d, J = 3.2 Hz, 1H), 6.02 (d, J = 0.8, 3.2 Hz, 1H), 4.27 (s, 4H), 4.10 (s, 3H), 3.48-3.39 (m, 2H), 3.19-3.10 (m, 2H), 2.82-2.74 (m, 2H), 2.74-2.63 (m, 1H), 2.34-2.21 (m, 2H), 2.10-2.01 (m, 2H), 1.87-1.73 (m, 2H).13CNMR (CDCl3, 100 MHz) δ: 162.56, 158.77, 157.44 (d, J = 255.3 Hz), 151.97, 143.76, 142.89, 141.80 (d, J = 6.9 Hz), 140.30, 138.66 (d, J = 2.1 Hz), 138.06 (d, J = 28.1 Hz), 125.34, 117.60, 117.08, 115.34 (d, J = 2.7 Hz), 112.59, 105.41, 104.48, 64.60, 64.57, 57.56, 53.97, 53.36, 35.61, 30.99, 21.10. HRMS (ESI) m / z calc’d for C28H28FN3O4[M+H]+: 490.21366; found: 490.21320. UPLC: rt: 3.782 min, purity: 97.06%. Example 3. 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4- yl)furan-2-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 6-(5-(piperidin-4-yl)furan-2-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one using General Procedure 3. Purification by flash chromatography (compound eluted in 50% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a off white solid (4 mg, 0.008 mmol, 7% yield).1HNMR (CDCl3, 400 MHz, contaminated with DCM) δ: Attorney Docket No.103361-644WO1 8.62 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.90 (s, 1H), 7.23 (dd, J = 7.3, 9.2Hz, 1H), 7.07 (d, J = 9.0 Hz, 1H), 7.03 (d, J = 1.9 Hz, 1H), 6.96 (d, J = 8.4 Hz, 1H), 6.45 (d, J = 3.3 Hz, 1H), 6.05 (d, J = 3.2 Hz, 1H), 4.63 (s, 2H), 4.09 (s, 3H), 3.46-3.41 (m, 2H), 3.20-3.12 (m, 2H), 2.82-2.76 (m, 2H), 2.69 (tt, J = 4.4, 11.8 Hz, 1H), 2.27 (td, J = 2.4, 12.1 Hz, 2H), 2.08-2.01 (m, 2H), 1.79 (qd, J = 1.8, 12.6 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 165.31, 162.57, 159.40, 157.47 (d, J = 255.5 Hz), 151.18, 142.72, 141.82 (d, J = 6.9 Hz), 140.32, 138.68 (d, J = 2.0 Hz), 138.06 (d, J = 28.2 Hz,), 130.71 (d, J = 12.8 Hz), 126.52 (d, J = 21.4 Hz), 119.60, 117.33, 115.37 (d, J = 2.7 Hz), 110.85, 105.67, 105.36, 67.59, 57.54, 53.96, 53.37, 35.66, 31.05, 29.85, 21.16. HRMS (ESI) m / z calc’d for C28H27FN4O4[M+H]+: 503.20891; found: 503.20862. UPLC: rt: 3.411 min, purity: 96%. tert-butyl 4-(5-(p-tolyl)-1H-pyrrol-2-yl)piperidine-1-carboxylate (6a) Title compound was synthesized from tert-butyl 4-(4-oxo-4-(p-tolyl)butanoyl)piperidine-1- carboxylate using General Procedure 4. Purification by flash chromatography (compound eluted in 10% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as a yellow oil (120 mg, 0.352 mmol, 58% yield).1HNMR (CDCl3, 400 MHz) δ: 8.08 (s, 1H), 7.33 (d, J = 8.1 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 6.36 (t, J = 3.1 Hz, 1H), 5.98 (t, J = 2.8 Hz, 1H), 4.25-4.13 (m, 2H), 2.89-2.80 (m, 2H), 2.80-2.72 (m, 1H), 2.34 (s, 3H), 2.00-1.94 (m, 2H), 1.62 (qd, J = 4.0, 12.4 Hz, 2H), 1.48 (s, 9H). tert-butyl 4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrrol-2-yl)piperidine-1- carboxylate (6b) Title compound was synthesized from tert-butyl 4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)- 4-oxobutanoyl)piperidine-1-carboxylate using General Procedure 4. Purification by flash Attorney Docket No.103361-644WO1 chromatography (compound eluted in 10% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a yellow oil (65 mg, 0.169 mmol, 68% yield).1HNMR (CDCl3, 400 MHz, contaminated with DCM and ethyl acetate) δ: 8.00 (s, 1H), 6.94-6.90 (m, 2H), 6.84 (d, J = 8.1 Hz, 1H), 6.28 (t, J = 3.2 Hz, 1H), 5.95 (t, J = 2.8 Hz, 1H), 4.27 (s, 4H), 4.23-4.14 (m, 2H, obscured by ethyl acetate), 2.89-2.70 (m, 3H), 2.00-1.92 (m, 2H), 1.67-1.55 (m, 2H, obscured by water), 1.47 (s, 9H). tert-butyl 4-(5-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1H-pyrrol-2- yl)piperidine-1-carboxylate (6c) Title compound was synthesized from tert-butyl 4-(4-oxo-4-(3-oxo-3,4-dihydro-2H- benzo[b][1,4]oxazin-6-yl)butanoyl)piperidine-1-carboxylate using General Procedure 4. Purification by flash chromatography (compound eluted in 40% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a yellow oil (35 mg, 0.088 mmol, 41% yield).1HNMR (CDCl3, 400 MHz) δ: 8.07 (s, 1H), 7.73 (s, 1H), 7.03 (dd, J = 2.0, 8.4 Hz, 1H), 6.96 (d, J = 8.4 Hz, 1H), 6.84 (d, J = 2.0 Hz, 1H), 6.31 (t, J = 3.3 Hz, 1H), 5.98 (t, J = 2.9 Hz, 1H), 4.62 (s, 2H), 4.25-4.14 (m, 2H), 2.89-2.71 (m, 3H), 2.00-1.92 (m, 2H), 1.68-1.55 (m, 2H, obscured by water), 1.48 (s, 9H). 4-(5-(p-tolyl)-1H-pyrrol-2-yl)piperidine (7a) Title compound was synthesized from tert-butyl 4-(5-(p-tolyl)-1H-pyrrol-2-yl)piperidine-1- carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a purple solid. No purification or isolation attempted. 4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrrol-2-yl)piperidine (7b) Attorney Docket No.103361-644WO1 Title compound was synthesized from tert-butyl 4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)- 1H-pyrrol-2-yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as an orange solid. No purification or isolation attempted. 6-(5-(piperidin-4-yl)-1H-pyrrol-2-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (7c) Title compound was synthesized from tert-butyl 4-(5-(3-oxo-3,4-dihydro-2H- benzo[b][1,4]oxazin-6-yl)-1H-pyrrol-2-yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a red solid. No purification or isolation attempted. Example 4. 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-pyrrol-2-yl)piperidin-1-yl)ethyl)- 1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(5-(p-tolyl)-1H-pyrrol-2-yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 20% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as a yellow oil (30 mg, 0.0675 mmol, 50% yield).1HNMR (CDCl3, 400 MHz, contaminated with DMSO) δ: 8.62 (s, 1H), 8.21 (s, 1H), 8.17 (d, J = 9.0 Hz, 1H), 7.32 (d, J = 8.2 Hz, 2H), 7.14 (d, J = 7.9Hz, 2H), 7.07 (d, J = 9.0 Hz, 1H), 6.36 (t, J = 3.2 Hz, 1H), 5.98 (t, J = 2.8 Hz, 1H), 4.09 (s, 3H), 3.46-3.40 (m, 2H), 3.21- Attorney Docket No.103361-644WO1 3.15 (m, 2H), 2.81-2.75 (m, 2H), 2.68-2.59 (m, obscured by DMSO, 1H), 2.33 (s, 3H), 2.24 (td, J = 2.2, 11.7 Hz, 2H), 2.04-1.97 (m, 2H), 1.79 (qd, J = 4.8, 13.3 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 162.54, 157.42 (d, J = 255.3 Hz), 141.78 (d, J = 6.9 Hz), 140.28, 138.65 (d, J = 2.1 Hz), 138.18, 137.90, 137.61, 135.54, 130.93, 130.71, 130.59, 130.38, 129.60, 123.60, 115.34 (d, J = 2.7 Hz), 105.50, 105.37, 57.54, 53.94, 53.72, 41.14, 35.40, 32.72, 21.21, 21.14. HRMS (ESI) m / z calc’d for C27H30FN4O [M+H]+: 445.23982; found: 445.23871. UPLC: rt: 3.926 min, purity: 97.7%. Example 5. 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrrol-2-yl)piperidin-1- yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrrol-2-yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 60% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a yellow solid (22 mg, 0.045 mmol, 50% yield).1HNMR (CDCl3, 400 MHz, contaminated with DMSO) δ: 8.60 (s, 1H), 8.23 (s, 1H), 8.17 (d, J = 9.0 Hz, 1H), 7.06 (d, J = 9.0 Hz, 1H), 6.95-6.89 (m, 2H), 6.82 (d, J = 8.2 Hz, 1H), 6.27 (t, J = 2.9 Hz, 1H), 5.95 (t, J = 2.8 Hz, 1H), 4.25 (s, 4H), 4.09 (s, 3H), 3.46-3.39 (m, 2H), 3.21-3.13 (m, 2H), 2.81-2.74 (m, 2H), 2.65-2.57 (m, obscured by DMSO, 1H), 2.28-2.18 (m, 2H), 2.04-1.95 (m, 2H), 1.79 (qd, J = 3.5, 12.4 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 162.53, 157.40 (d, J = 255.3 Hz), 143.86, 142.03, 141.77 (d, J = 7.0 Hz), 140.26, 138.63 (d, J = 2.1 Hz), 138.02 (d, J = 28.1 Hz), 137.45, 130.71, 130.62 (d, J = 18.9 Hz), 127.19, 117.70, 117.10, 115.33 (d, J = 2.7 Hz), 112.60, 105.37, 105.12, 64.59, 64.52, 57.51, 53.93, 53.69, 41.12, 35.35, 32.66, 21.11. HRMS (ESI) m / z calc’d for C28H29FN4O3[M+H]+: 489.22965; found: 489.22922. UPLC: rt: 3.661 min, purity: 95.6%. Example 6. 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)- 1H-pyrrol-2-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 6-(5-(piperidin-4-yl)-1H-pyrrol-2-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one using General Procedure 3. Purification by flash chromatography (compound eluted in 0.3% methanol in DCM) and concentration in vacuo afforded the title compound as a yellow oil (7 mg, 0.014 mmol, 25% yield).1HNMR (CDCl3, 400 MHz, contaminated with DMSO) δ: 8.63 (s, 1H), 8.31 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 8.01 (s, 1H), 7.08 (d, J = 9.0 Hz, 1H), 7.02 (dd, Attorney Docket No.103361-644WO1 J = 2.0, 8.4 Hz, 1H), 6.95 (d, J = 8.4 Hz, 1H), 6.87 (d, J = 2.0 Hz, 1H), 6.30 (t, J = 2.8 Hz, 1H), 5.98 (t, J = 2.9 Hz, 1H), 4.61 (s, 2H), 4.10 (s, 3H), 3.51-3.43 (m, 2H), 3.28-3.20 (m, 2H), 2.88- 2.81 (m, 2H), 2.71-2.62 (m, obscured by DMSO, 1H), 2.35-2.26 (m, 2H), 2.05-1.97 (m, 2H), 1.95-1.81 (m, 2H).13CNMR (CDCl3, 100 MHz) δ: 165.51, 162.64, 157.43 (d, J = 255.7 Hz), 141.98, 141.74 (d, J = 6.9 Hz), 140.35, 138.71 (d, J = 1.8 Hz), 138.21, 137.93, 137.80, 129.98, 128.51, 126.66, 119.45, 117.39, 115.45 (d, J = 2.5 Hz), 111.23, 105.92, 105.83, 67.58, 57.36, 54.01, 53.68, 41.17, 35.28, 32.43, 20.92. HRMS (ESI) m / z calc’d for C28H28FN5O3[M+H]+: 502.22489; found: 502.22440. UPLC: rt: 3.389 min, purity: 97.8%. abtert-butyl 4-(2-(p-tolyl)oxazol-5-yl)piperidine-1-carboxylate (9a) Title compound was synthesized from tert-butyl 4-(2-bromoacetyl)piperidine-1-carboxylate and p-tolylmethanamine using General Procedure 6. Purification by flash chromatography (compound eluted in 10% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as a clear oil (65 mg, 0.190 mmol, 19% yield).1HNMR (CDCl3, 400 MHz) δ: 7.88 (d, J = 8.2 Hz, 2H), 7.26-7.23 (m, 2H, obscured by chloroform), 6.82 (d, J = 1.0 Hz, 1H), 4.21- 4.10 (m, 2H), 2.96-2.85 (m, 2H), 2.44 (t, J = 6.1 Hz, 1H), 2.40 (s, 3H), 2.07-1.99 (m, 2H), 1.66 (qd, J = 4.2, 12.0 Hz, 2H), 1.48 (s, 9H). tert-butyl 4-(2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)oxazol-5-yl)piperidine-1-carboxylate (9b) Title compound was synthesized from tert-butyl 4-(2-bromoacetyl)piperidine-1-carboxylate and (2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methanamine using General Procedure 6. Purification by flash chromatography (compound eluted in 18% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as a yellow oil (59 mg, 0.153 mmol, 15% Attorney Docket No.103361-644WO1 yield).1HNMR (CDCl3, 400 MHz, contaminated with grease) δ: 7.51-7.47 (m, 2H), 6.93-6.90 (m, 1H), 6.79 (d, J = 1.0 Hz, 1H), 4.30 (s, 4H), 4.20-4.09 (m, 2H), 2.95-2.83 (m, 3H), 2.05- 1.97 (m, 2H), 1.64 (qd, J = 3.6, 11.3 Hz, 2H), 1.48 (s, 9H). ab5-(piperidin-4-yl)-2-(p-tolyl)oxazole (10a) Title compound was synthesized from tert-butyl 4-(2-(p-tolyl)oxazol-5-yl)piperidine-1- carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a yellow solid. No purification or isolation attempted. 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(piperidin-4-yl)oxazole (10b) Title compound was synthesized from tert-butyl 4-(2-(2,3-dihydrobenzo[b][1,4]dioxin-6- yl)oxazol-5-yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as an orange solid. No purification or isolation attempted.

[0002] Attorney Docket No.103361-644WO1 Example 7.5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-2-(p- tolyl)oxazole Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 5-(piperidin-4-yl)-2-(p-tolyl)oxazole using General Procedure 3. Purification by flash chromatography (compound eluted in 50% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as a yellow oil (30 mg, 0.0672 mmol, 49% yield).1HNMR (CDCl3, 400 MHz, contaminated with DCM) δ: 8.63 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.88 (d, J = 8.2 Hz, 2H), 7.26-7.23 (m, 2H, obscured by chloroform), 7.08 (d, J = 9.0 Hz, 1H), 6.81 (d, J = 1.0 Hz, 1H), 4.10 (s, 3H), 3.46-3.40 (m, 2H), 3.19-3.12 (m, 2H), 2.82- 2.72 (m, 3H), 2.40 (s, 3H), 2.32-2.24 (m, 2H), 2.10-2.03 (m, 2H), 1.82 (qd, J = 3.2, 11.9 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 162.54, 160.95, 157.41 (d, J = 255.5 Hz), 155.83, 141.74 (d, J = 7.0 Hz), 140.30, 140.26, 138.65 (d, J = 1.9 Hz), 138.03 (d, J = 28.2 Hz), 130.56, 130.43, 129.52, 126.09, 125.26, 122.32, 115.34 (d, J = 2.5 Hz), 57.44, 53.92, 53.09, 33.59, 30.54, 21.58, 21.09. HRMS (ESI) m / z calc’d for C26H27FN4O2[M+H]+: 447.21908; found: 447.21848. UPLC: rt: 3.61 min, purity: 91.51%. Example 8. 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(1-(2-(3-fluoro-6-methoxy-1,5- naphthyridin-4-yl)ethyl)piperidin-4-yl)oxazole Attorney Docket No.103361-644WO1 Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(piperidin-4-yl)oxazole using General Procedure 3. Purification by flash chromatography (compound eluted in 60% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as a white solid (8 mg, 0.0163 mmol, 14% yield).1HNMR (CDCl3, 400 MHz) δ: 8.62 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.51-7.48 (m, 2H), 7.08 (d, J = 9.0 Hz, 1H), 6.93-6.89 (m, 1H), 6.78 (d, J = 1.0 Hz, 1H), 4.30 (s, 4H), 4.10 (s, 3H), 3.46-3.40 (m, 2H), 3.18-3.11 (m, 2H), 2.82-2.70 (m, 3H), 2.28 (qd, J = 2.5, 11.9 Hz, 2H), 2.09-2.01 (m, 2H), 1.81 (qd, J = 3.6, 12.1 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 161.54 (d, J = 207.7 Hz), 156.19, 155.81, 145.46, 143.80, 141.83, 140.33, 138.69, 138.22, 137.94, 130.71, 130.58122.27, 121.62, 119.78, 117.78, 115.39, 64.69, 64.43, 57.52, 53.95, 53.15, 33.64, 30.60, 21.17. HRMS (ESI) m / z calc’d for C27H27FN4O4 [M+H]+: 491.20891; found: 491.20825. UPLC: rt: 3.42 min, purity: 93.3%. tert-butyl 4-(5-(p-tolyl)isoxazol-3-yl)piperidine-1-carboxylate (13a) Title compound was synthesized from tert-butyl 4-formylpiperidine-1-carboxylate and 1- ethynyl-4-methylbenzene using General Procedure 7. Purification by flash chromatography (compound eluted in 56% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as a white solid (140 mg, 0.409 mmol, 27% yield).1HNMR (CDCl3, 400 MHz) δ: 7.65 (d, J = 8.2 Hz, 2H), 7.26 (d, J = 7.9 Hz, 2H, partially obscured by chloroform), 6.33 (s, 1H), 4.23-4.10 (m, 2H), 3.00-2.84 (m, 3H), 2.40 (s, 3H), 2.02-1.94 (m, 2H), 1.70 (qd, J = 4.2, 11.9 Hz, 2H), 1.48 (s, 9H). Attorney Docket No.103361-644WO1 tert-butyl 4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)isoxazol-3-yl)piperidine-1- carboxylate (13b) Title compound was synthesized from tert-butyl 4-formylpiperidine-1-carboxylate and 6- ethynyl-2,3-dihydrobenzo[b][1,4]dioxine using General Procedure 7. Purification by flash chromatography (compound eluted in 10% ethyl acetate in hexanes) and concentration in vacuo afforded an impure mixture of the title compound plus impurities as a yellow oil (98 mg, 0.254 mmol, 16% yield). tert-butyl 4-(5-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)isoxazol-3-yl)piperidine- 1-carboxylate (13c) Title compound was synthesized from tert-butyl 4-formylpiperidine-1-carboxylate and 6- ethynyl-2H-benzo[b][1,4]oxazin-3(4H)-one using General Procedure 7. Purification by flash chromatography (compound eluted in 40% ethyl acetate in hexanes) and concentration in vacuo afforded an impure mixture of the title compound plus impurities as a yellow oil (42 mg, 0.105 mmol, 18% yield). 3-(piperidin-4-yl)-5-(p-tolyl)isoxazole (14a) Title compound was synthesized from tert-butyl 4-(5-(p-tolyl)isoxazol-3-yl)piperidine-1- carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a yellow solid. No purification or isolation attempted. 5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-(piperidin-4-yl)isoxazole (14b) Attorney Docket No.103361-644WO1 Title compound was synthesized from tert-butyl 4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6- yl)isoxazol-3-yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as an orange solid. No purification or isolation attempted. 6-(3-(piperidin-4-yl)isoxazol-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (14c) Title compound was synthesized from tert-butyl 4-(5-(3-oxo-3,4-dihydro-2H- benzo[b][1,4]oxazin-6-yl)isoxazol-3-yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as an orange solid. No purification or isolation attempted. Example 9.3-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-5-(p- tolyl)isoxazole Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and piperidine 3-(piperidin-4-yl)-5-(p-tolyl)isoxazole using General Procedure 3. Purification by flash chromatography (compound eluted in 40% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as an off-white solid (15 mg, 0.0336 mmol, 25% yield).1HNMR (CDCl3, 400 MHz) δ: 8.62 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.65 (d, J = 8.2 Hz, 2H), 7.26-7.23 (m, 2H, obscured by chloroform), 7.08 (d, J = 9.0 Hz, 1H), Attorney Docket No.103361-644WO1 6.34 (s, 1H), 4.10 (s, 3H), 3.47-3.41 (m, 2H), 3.21-3.15 (m, 2H), 2.87-2.77 (m, 3H), 2.40 (s, 3H), 2.28 (td, J = 2.2, 11.6 Hz, 2H), 2.05-1.98 (m, 2H), 1.85 (qd, J = 3.7, 12.0 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 169.99, 168.08, 162.58, 157.48 (d, J = 255.2 Hz), 141.82 (d, J = 6.8 Hz), 140.42, 140.33, 138.68, 138.21, 137.93, 130.70 (d, J = 13.0 Hz), 129.76, 125.86, 125.12, 115.37 (d, J = 2.7 Hz), 97.15, 57.54, 53.96, 53.39, 34.25, 31.55, 21.62, 21.16. HRMS (ESI) m / z calc’d for C26H28FN4O2[M+H]+: 447.21908; found: 447.21838. UPLC: rt: 3.777 min, purity: 97.3%. Example 10. 5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-(1-(2-(3-fluoro-6-methoxy-1,5- naphthyridin-4-yl)ethyl)piperidin-4-yl)isoxazole Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-(piperidin-4-yl)isoxazole using General Procedure 3. Purification by flash chromatography (compound eluted in 50% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a yellow solid (15 mg, 0.0306 mmol, 18.8% yield).1HNMR (CDCl3, 400 MHz, impure, contaminated with DMSO) δ: 8.61 (s, 1H), 8.17 (d, J = 9.0 Hz, 1H), 7.27-7.25 (m, obscured by CDCl3, 1H), 7.23 (dd, J = 2.1, 8.4 Hz, 1H), 7.06 (d, J = 9.0 Hz, 1H), 6.91 (d, J = 8.4 Hz, 1H), 6.25 (s, 1H), 4.28 (s, 4H), 4.09 (s, 3H), 3.45-3.40 (m, 2H), 3.20-3.14 (m, 2H), 2.84-2.71 (m, 3H), 2.27 (td, J = 2.2, 11.6 Hz, 2H), 2.03-1.96 (m, 2H), 1.83 (qd, J = 2.6, 12.0 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 169.46, 168.03, 162.53, 157.42 (d, J = 255.3 Hz), 154.59, 145.37, 143.88, 141.76 (d, J = 7.1 Hz), 140.26, 138.62 (d, J = 2.0 Hz), 138.01 (d, J = 28.0 Hz), 130.64 (d, J = 13.0 Hz), 121.36, 119.45, 117.93, 115.34 (d, J = 2.6 Hz), 115.00, 96.75, 64.64, 64.41, 57.47, 53.93, 53.33, 41.12, 34.18, 31.43, 21.08. HRMS (ESI) m / z calc’d for C27H27FN4O4[M+H]+: 491.20891; found: 491.20847. UPLC: rt: 3.568 min, purity: 90.33%. Example 11. 6-(3-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4- yl)isoxazol-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 6-(3-(piperidin-4-yl)isoxazol-5-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one using General Procedure 3. Purification by flash chromatography (compound eluted in 80% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (14 mg, 0.0278 mmol, 26% yield).1HNMR (CDCl3, 400 MHz, contaminated with DCM) δ: 8.62 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.59 (s, 1H), 7.36 (dd, J = 2.0, 8.4 Hz, 1H), 7.21 (d, J Attorney Docket No.103361-644WO1 = 1.9 Hz, 1H), 7.08 (d, J = 9.0 Hz, 1H), 7.05 (d, J = 8.4 Hz, 1H), 6.31 (s, 1H), 4.68 (s, 2H), 4.10 (s, 3H), 3.47-3.40 (m, 2H), 3.21-3.15 (m, 2H), 2.87-2.76 (m, 3H), 2.28 (td, J = 2.6, 11.9 Hz, 2H), 2.04-1.97 (m ,2H), 1.83 (qd, J = 3.1, 11.7 Hz, 2H).13CNMR ([CD3]2SO, 100 MHz) δ: 168.01, 167.88, 164.43, 162.00, 156.84 (d, J = 254.2 Hz), 144.63, 140.92 (d, J = 7.2 Hz), 140.42, 138.10 (d, J = 2.3 Hz), 137.88 (d, J = 27.9 Hz), 130.01 (d, J = 13.0 Hz), 129.17, 127.79, 125.83, 121.37, 120.94, 116.89, 115.30 (d, J = 2.6 Hz), 112.36, 98.08, 66.72, 56.77, 53.57, 52.55, 33.51, 30.70, 20.65 HRMS (ESI) m / z calc’d for C27H26FN5O4[M+H]+: 504.20416; found: 504.20386. UPLC: rt: 3.261 min, purity: 93.31%. tert-butyl 4-(3-(p-tolyl)isoxazol-5-yl)piperidine-1-carboxylate (17a) Title compound was synthesized from tert-butyl 4-ethynylpiperidine-1-carboxylate and 4- methylbenzaldehyde using General Procedure 7. Purification by flash chromatography (compound eluted in 5% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as a yellow oil (70 mg, 0.204 mmol, 14% yield).1HNMR (CDCl3, 400 MHz) δ: 7.67 (d, J = 8.1 Hz, 2H), 7.26-7.23 (m, 2H, obscured by chloroform), 6.26 (s, 1H), 4.24-4.09 (m, 2H), 3.03-2.85 (m, 3H), 2.44-2.37 (m, 3H), 2.10-2.02 (m, 2H), 1.69 (qd, J = 3.9, 11.8 Hz, 2H), 1.48 (s, 9H). tert-butyl 4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)isoxazol-5-yl)piperidine-1- carboxylate (17b) Title compound was synthesized from tert-butyl 4-ethynylpiperidine-1-carboxylate and 2,3- dihydrobenzo[b][1,4]dioxine-6-carbaldehyde using General Procedure 7. Purification by flash chromatography (compound eluted in 5% ethyl acetate in hexane) and concentration in vacuo Attorney Docket No.103361-644WO1 afforded the title compound as a yellow oil (120 mg, 0.311 mmol, 21% yield).1HNMR (CDCl3, 400 MHz) δ: 7.31 (d, J = 2.0 Hz, 1H), 7.28-7.25 (m, 1H, obscured by chloroform), 6.92 (d, J = 8.4 Hz, 1H), 6.19 (d, J = 0.6 Hz, 1H), 4.32-4.27 (m, 5H), 4.21-4.10 (m, 2), 3.00-2.85 (m, 3H), 2.09-2.02 (m, 2H), 1.67 (qd, J = 4.1, 12.1 Hz, 2H), 1.47 (s, 9H). tert-butyl 4-(3-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)isoxazol-5-yl)piperidine- 1-carboxylate (17c) Title compound was synthesized from tert-butyl 4-ethynylpiperidine-1-carboxylate and 3-oxo- 3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbaldehyde using General Procedure 7. Purification by flash chromatography (compound eluted in 30% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (150 mg, 0.376 mmol, 25% yield).1HNMR (CDCl3, 400 MHz, contaminated with DCM and methanol) δ: 8.09 (s, 1H), 7.35 (dd, J = 2.0, 8.2 Hz, 1H), 7.33 (d, J = 1.7 Hz, 1H), 7.04 (d, J = 8.2 Hz, 1H), 6.23 (d, J = 0.7 Hz, 1H), 4.67 (s, 2H), 4.21-4.13 (m, 2H), 2.98 (tt, J = 3.6, 11.4 Hz, 1H), 2.94-2.86 (m, 2H), 2.10-2.03 (m, 2H), 1.68 (qd, J = 4.2, 11.9 Hz, 2H), 1.48 (s, 9H). 5-(piperidin-4-yl)-3-(p-tolyl)isoxazole (18a) Title compound was synthesized from tert-butyl 4-(3-(p-tolyl)isoxazol-5-yl)piperidine-1- carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a yellow solid. No purification or isolation attempted. 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(piperidin-4-yl)isoxazole (18b) Attorney Docket No.103361-644WO1 Title compound was synthesized from tert-butyl 4-(3-(2,3-dihydrobenzo[b][1,4]dioxin-6- yl)isoxazol-5-yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a yellow solid. No purification or isolation attempted. 6-(5-(piperidin-4-yl)isoxazol-3-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (18c) Title compound was synthesized from tert-butyl 4-(3-(3-oxo-3,4-dihydro-2H- benzo[b][1,4]oxazin-6-yl)isoxazol-5-yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as an off-white solid. No purification or isolation attempted. Example 12. 5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-3- (p-tolyl)isoxazole Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 5-(piperidin-4-yl)-3-(p-tolyl)isoxazole using General Procedure 3. Purification by flash chromatography (compound eluted in 40% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as a white solid (24 mg, 0.0537 mmol, 39% yield).1HNMR (CDCl3, 400 MHz) δ: 8.62 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.68 (d, J = 8.1 Hz, 2H), 7.26-7.22 (m, 2H, obscured by chloroform), 7.08 (d, J = 9.0 Hz, 1H), 6.25 (d, J = 0.6 Attorney Docket No.103361-644WO1 Hz, 1H), 4.09 (s, 3H), 3.46-3.39 (m, 2H), 3.18-3.12 (m, 2H), 2.88-2.76 (m, 3H), 2.39 (s, 3H), 2.29 (td, J = 2.6, 12.0 Hz, 2H), 2.14-2.06 (m, 2H), 1.83 (qd, J = 3.6, 11.8 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 177.02, 162.58, 162.36, 157.47 (d, J = 255.2 Hz), 141.80 (d, J = 7.1 Hz), 140.34, 140.08, 138.69, 138.21, 137.93, 130.62 (d, J = 13.2 Hz), 129.70, 126.80, 126.66, 115.38 (d, J = 2.8 Hz), 97.49, 57.46, 53.95, 53.11, 34.73, 30.67, 21.56, 21.17. HRMS (ESI) m / z calc’d for C26H28FN4O2[M+H]+: 447.21908; found: 447.21857. UPLC: rt: 3.737 min, purity: 94.2%. Example 13. 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(1-(2-(3-fluoro-6-methoxy-1,5- naphthyridin-4-yl)ethyl)piperidin-4-yl)isoxazole Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(piperidin-4-yl)isoxazole using General Procedure 3. Purification by flash chromatography (compound eluted in 72% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as an off-white solid (20 mg, 0.0408 mmol, 30% yield).1HNMR (CDCl3, 400 MHz) δ: 8.65 (s, 1H), 8.20 (d, J = 9.0 Hz,1H), 7.34 (d, J = 2.0 Hz, 1H), 7.32-7.28 (m, 1H, obscured by chloroform), 7.10 (d, J = 9.0 Hz, 1H), 6.94 (d, J = 8.3 Hz, 1H), 6.21 (d, J = 0.7 Hz, 1H), 4.32 (s, 4H), 4.12 (s, 3H), 3.48-3.42 (m, 2H), 3.21-3.15 (m, 2H), 2.89-2.78 (m, 3H), 2.31 (td, J = 2.9, 12.3 Hz, 2H), 2.15- 2.08 (m, 2H), 1.84 (qd, J = 3.7, 11.6 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 176.92, 162.56, 161.87, 157.44 (d, J = 255.3 Hz), 145.18, 143.89, 141.76 (d, J = 6.9 Hz), 140.31, 138.66 (d, J = 2.1 Hz), 138.04 (d, J = 28.1 Hz), 130.55 (d, J = 13.0 Hz), 122.87, 120.25, 117.81, 115.91, 115.35 (d, J = 2.7 Hz), 97.42, 64.63, 64.43, 57.41, 53.93, 53.06, 54.17, 34.67, 30.59, 21.12. HRMS (ESI) m / z calc’d for C27H27FN4O4[M+H]+: 491.20891; found: 491.20840. UPLC: rt: 3.555 min, purity: 95.4%. Example 14. 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4- yl)isoxazol-3-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 6-(5-(piperidin-4-yl)isoxazol-3-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one using General Procedure 3. Purification by flash chromatography (compound eluted in 1% methanol in DCM) and concentration in vacuo afforded the title compound as a white solid (7 mg, 0.0139 mmol, 8% yield).1HNMR (CDCl3, 400 MHz, contaminated with ethyl acetate) δ: 8.62 (s, 1H), 8.38 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.38-7.32 (m, 2H), 7.07 (d, J = 9.0 Hz, 1H), Attorney Docket No.103361-644WO1 7.03 (d, J = 8.2 Hz, 1H), 6.22 (s, 1H), 4.67 (s, 2H), 4.09 (s, 3H), 3.49-3.40 (m, 2H), 3.23-3.14 (m, 2H), 2.89-2.77 (m, 3H), 2.38-2.25 (m, 2H), 2.17-2.07 (m, 2H), 1.93-1.78 (m, 2H).13CNMR (CDCl3, 100 MHz, contaminated with ethyl acetate) δ: 177.34, 165.16, 162.61, 161.38, 157.45 (d, J = 255.3 Hz), 145.06, 141.75 (d, J = 7.0 Hz), 140.33, 138.68 (d, J = 2.0 Hz), 138.19, 137.91, 126.69, 124.24, 123.05, 117.36, 115.42, 114.14, 97.43, 67.45, 57.32, 53.96, 53.01, 34.65, 30.50, 21.19. HRMS (ESI) m / z calc’d for C27H26FN5O4[M+H]+: 504.20416; found: 504.20407. UPLC: rt: 3.234 min, purity: 95.85%. tert-butyl 4-(1-(p-tolyl)-1H-1,2,3-triazol-4-yl)piperidine-1-carboxylate (20a) Title compound was synthesized from tert-butyl 4-ethynylpiperidine-1-carboxylate and p- tolylboronic acid using General Procedure 8. Concentration in vacuo afforded the title compound as an off-white solid (450 mg, 1.31 mmol, 88% yield, not completely pure).1HNMR (CDCl3, 400 MHz) δ: 7.66 (s, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 4.27-4.11 (m, 2H), 2.97 (tt, J = 4.2, 12.1 Hz, 1H), 2.96-2.85 (m, 2H), 2.42 (s, 3H), 2.12-2.05 (m, 2H), 1.67 (qd, J = 4.1, 12.1 Hz, 2H), 1.47 (s, 9H). tert-butyl 4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-4-yl)piperidine-1- carboxylate (20b) Title compound was synthesized from tert-butyl 4-ethynylpiperidine-1-carboxylate and (2,3- dihydrobenzo[b][1,4]dioxin-6-yl)boronic acid using General Procedure 8. Concentration in vacuo afforded the title compound as a yellow oil (580 mg, 1.5 mmol, 100% yield). No purification attempted, compound has excess piperidine starting material present. Attorney Docket No.103361-644WO1 tert-butyl 4-(1-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1H-1,2,3-triazol-4- yl)piperidine-1-carboxylate (20c) Title compound was synthesized from tert-butyl 4-ethynylpiperidine-1-carboxylate and (3- oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)boronic acid using General Procedure 8. Purification by flash chromatography (compound eluted in 20% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as an off white solid (40 mg, 0.1 mmol, 10% yield).1HNMR (CDCl3, 400 MHz) δ: 10.04 (s, 1H), 8.01 (d, J = 2.4 Hz, 1H), 7.70 (s, 1H), 7.13 (dd, J = 2.4, 8.6 Hz, 1H), 7.07 (d, J = 8.6 Hz, 1H), 4.68 (s, 2H), 4.27-4.14 (m, 2H), 3.12 (tt, J = 3.6, 11.8 Hz, 1H), 3.00-2.87 (m, 2H), 2.20-2.09 (m, 2H), 1.65 (dq, J = 4.0, 12.4 Hz, 2H), 1.48 (s, 9H). 4-(1-(p-tolyl)-1H-1,2,3-triazol-4-yl)piperidine (21a) Title compound was synthesized from tert-butyl 4-(1-(p-tolyl)-1H-1,2,3-triazol-4- yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a yellow solid. No purification or isolation attempted. 4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-4-yl)piperidine (21b) Title compound was synthesized from tert-butyl 4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)- 1H-1,2,3-triazol-4-yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a yellow solid. No purification or isolation attempted. 6-(4-(piperidin-4-yl)-1H-1,2,3-triazol-1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (21c) Attorney Docket No.103361-644WO1 Title compound was synthesized from tert-butyl 4-(1-(3-oxo-3,4-dihydro-2H- benzo[b][1,4]oxazin-6-yl)-1H-1,2,3-triazol-4-yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a yellow solid. No purification or isolation attempted. Example 15. 7-fluoro-2-methoxy-8-(2-(4-(1-(p-tolyl)-1H-1,2,3-triazol-4-yl)piperidin-1- yl)ethyl)-1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(1-(p-tolyl)-1H-1,2,3-triazol-4-yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 40% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (3.5 mg, 0.00784 mmol, 5% yield).1HNMR (CDCl3, 400 MHz) δ: 8.62 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.66 (s, 1H), 7.59 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.1 Hz, 2H), 7.07 (d, J = 9.0 Hz, 1H), 4.10 (s, 3H), 3.47- 3.40 (m, 2H), 3.22-3.14 (m, 2H), 2.89 (tt, J = 3.8, 11.7 Hz, 1H), 2.83-2.77 (m, 2H), 2.41 (s, 3H), 2.31 (td, J = 1.9, 11.6 Hz, 2H), 2.17-2.10 (m, 2H), 1.80 (qd, J = 3.6, 12.3 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 162.58, 157.48 (d, J = 255.2 Hz), 153.16, 141.82 (d, J = 6.8 Hz), 140.31, 138.72, 138.68 (d, J = 2.0 Hz), 138.20, 137.92, 135.18, 130.80, 130.67, 130.32, 120.54, 117.80, Attorney Docket No.103361-644WO1 115.37 (d, J = 2.7 Hz), 57.54, 53.97, 53.55, 33.72, 32.37, 21.22, 21.15. HRMS (ESI) m / z calc’d for C25H28FN6O [M+H]+: 447.23031; found: 447.22992. UPLC: rt: 3.464 min, purity: 97.9%. Example 16. 8-(2-(4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-4- yl)piperidin-1-yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-4- yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 40% ethyl acetate in hexane) and concentration in vacuo afforded the title compound as a yellow solid (12 mg, 0.0668 mmol, 18% yield).1HNMR (CDCl3, 400 MHz, contaminated with DMSO) δ: 8.62 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.59 (s, 1H), 7.24 (d, J = 2.5 Hz, 1H), 7.16 (dd, J = 2.6, 8.7 Hz, 1H), 7.08 (d, J = 9.0 Hz, 1H), 6.96 (d, J = 8.7 Hz, 1H), 4.31 (s, 4H), 4.10 (s, 3H), 3.74-3.41 (m, 2H), 3.22-3.14 (m, 2H), 2.93-2.76 (m, 3H), 2.36-2.26 (m, 2H), 2.17- 2.08 (m, 2H), 1.85-1.72 (m, 2H).13CNMR (CDCl3, 100 MHz) δ: 162.59, 157.42 (d, J = 255.5 Hz), 152.85, 144.18, 143.94, 141.74 (d, J = 6.8 Hz), 140.30, 138.67 (d, J = 2.1 Hz), 138.04 (d, J = 28.1 Hz), 131.27, 118.08, 118.00, 115.39 (d, J = 2.6 Hz), 113.84, 110.33, 64.55, 64.48, 57.38, 54.00, 53.41, 41.17, 33.58, 32.13, 20.96. HRMS (ESI) m / z calc’d for C26H28FN6O3[M+H]+: 491.22014; found: 491.21927. UPLC: rt: 3.359 min, purity: 92.3%. Pd(PPh3)4CuI 6-((trimethylsilyl)ethynyl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (23d) Title compound was synthesized from 6-bromo-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one using General Procedure 9. Purification by flash chromatography (compound eluted in 10% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid Attorney Docket No.103361-644WO1 (150 mg, 0.609 mmol, 61% yield).1HNMR (CDCl3, 400 MHz) δ: 7.92 (s, 1H), 7.19 (dd, J = 0.6, 8.2 Hz, 1H), 7.14 (d, J = 8.2 Hz, 1H), 4.68 (s, 2H), 0.26 (s, 9H). 6-((trimethylsilyl)ethynyl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (23f) Title compound was synthesized from 6-bromo-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one using General Procedure 9. Purification by flash chromatography (compound eluted in 10% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a brown solid (120 mg, 0.485 mmol, 20% yield).1HNMR (CDCl3, 400 MHz) δ: 8.02 (s, 1H), 7.94 (s, 1H), 4.94 (s, 2H), 0.28 (s, 9H). 6-ethynyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (12d) Title compound was synthesized from 6-((trimethylsilyl)ethynyl)-2H-pyrido[3,2- b][1,4]oxazin-3(4H)-one using General Procedure 10. No purification attempted. Concentration in vacuo afforded the title compound as a crude brown solid (80 mg, 0.459 mmol, 94.3% yield). This was used directly in next step. 6-ethynyl-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (12f) Title compound was synthesized from 6-((trimethylsilyl)ethynyl)-2H-pyrazino[2,3- b][1,4]oxazin-3(4H)-one using General Procedure 10. Purification by flash chromatography (compound eluted in 40% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a brown solid (120 mg, 0.685 mmol, 53% yield).1HNMR ([CD3]2SO, 400 MHz, contaminated with DCM) δ: 11.71 (s, 1H), 7.95 (s, 1H), 4.92 (s, 2H), 4.42 (s, 1H). Attorney Docket No.103361-644WO1 4-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)piperidine (25a) Title compound was synthesized from tert-butyl 4-iodopiperidine-1-carboxylate and 1- ethynyl-4-methylbenzene using General Procedure 11. Purification by flash chromatography (compound eluted in 3% methanol in DCM) and concentration in vacuo afforded the title compound as a white solid (120 mg, 0.495 mmol, 50% yield).1HNMR (MeOD, 400 MHz) δ: 8.32 (s, 1H), 7.70 (d, J = 8.2 Hz, 2H), 7.25 (d, J = 7.9 Hz, 2H), 4.67 (tt, J = 2.6, 8.7 Hz, 1H), 3.25-3.18 (m, 2H), 2.81 (td, J = 2.6, 12.9 Hz, 2H), 2.37 (s, 3H), 2.25-2.17 (m, 2H), 2.04 (qd, J = 4.2, 12.0 Hz, 2H). 4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)piperidine (25b) Title compound was synthesized from tert-butyl 4-iodopiperidine-1-carboxylate and 6- ethynyl-2,3-dihydrobenzo[b][1,4]dioxine using General Procedure 11. Purification by flash chromatography (compound eluted in 3% methanol in DCM) and concentration in vacuo afforded the title compound as a white solid (50 mg, 0.175 mmol, 17% yield, a small amount of deprotected, iodo-piperidine present).1HNMR (MeOD, 400 MHz) δ: 8.26 (s, 1H), 7.31 (d, J = 2.0 Hz,1H), 7.27 (dd, J = 2.1, 8.4 Hz, 1H), 6.88 (d, J = 8.4 Hz, 1H), 4.65 (tt, J = 4.2, 11.6 Hz, 1H), 4.27 (s, 4H), 3.25-3.19 (m, 2H), 2.82 (td, J = 2.6, 12.9 Hz, 2H), 2.25-2.17 (m, 2H), 2.04 (qd, J = 4.2, 11.6 Hz, 2H). 6-(1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (25c) Title compound was synthesized from tert-butyl 4-iodopiperidine-1-carboxylate and 6- ethynyl-2H-benzo[b][1,4]oxazin-3(4H)-one using General Procedure 11. Purification by flash chromatography (compound eluted in 5% methanol in DCM) and concentration in vacuo Attorney Docket No.103361-644WO1 afforded the title compound as a white solid (16 mg, 0.0535 mmol, 6% yield).1HNMR (MeOD, 400 MHz) δ: 8.29 (s, 1H), 7.41-7.37 (m, 2H), 7.01 (d, J = 8.8 Hz, 1H), 4.73-4.64 (m, 1H), 4.61 (s, 2H), 3.30-3.21 (m, 2H, obscured by methanol), 2.87-2.79 (m, 2H), 2.26-2.20 (m, 2H), 2.11- 2.00 (m, 2H). 6-(1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (25d) Title compound was synthesized from tert-butyl 4-iodopiperidine-1-carboxylate and 6- ethynyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one using General Procedure 11. Purification by flash chromatography (compound eluted in 5% methanol in DCM) and concentration in vacuo afforded the title compound as a off-white solid (26 mg, 0.0866 mmol, 11.6% yield).1HNMR (CDCl3, 400 MHz) δ: 7.98 (s, 1H), 7.80 (d, J = 8.2 Hz, 1H), 7.34 (d, J = 8.3 Hz, 1H), 4.70 (s, 2H), 4.61 (tt, J = 4.1, 11.6 Hz, 1H), 3.31-3.25 (m, 2H), 2.82 (td, J = 2.6, 12.6 Hz, 2H), 2.28- 2.22 (m, 2H), 1.98 (qd, J = 3.9, 12.0 Hz, 2H). 4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)piperidine (25e) Title compound was synthesized from tert-butyl 4-iodopiperidine-1-carboxylate and 1,2- dichloro-4-ethynylbenzene using General Procedure 11. Purification by flash chromatography (compound eluted in 5% methanol in DCM) and concentration in vacuo afforded the title compound as a white solid (150 mg, 0.505 mmol, 50.5% yield).1HNMR (MeOD, 400 MHz) δ: 8.48 (s, 1H), 8.02 (d, J = 2.0 Hz, 1H), 7.76 (dd, J = 2.0, 8.4 Hz, 1H), 7.59 (d, J = 8.4 Hz, 1H), 4.69 (tt, J = 4.1, 11.6 Hz, 1H), 3.25-3.19 (m, 2H), 2.81 (td, J = 2.6, 12.9 Hz, 2H), 2.26-2.19 (m, 2H), 2.04 (qd, J = 4.2, 12.0 Hz, 2H).

[0003] Attorney Docket No.103361-644WO1 Example 17. 7-fluoro-2-methoxy-8-(2-(4-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)piperidin-1- yl)ethyl)-1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and piperidine 4-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 50% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as an orange solid (50 mg, 0.112 mmol, 59% yield).1HNMR (CDCl3, 400 MHz) δ: 8.64 (s, 1H), 8.19(d, J = 9.0 Hz, 1H), 7.73 (s, 1H), 7.71 (d, J = 8.1 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 9.0 Hz, 1H), 4.61- 4.50 (m, 1H), 4.10 (s, 3H), 3.50-3.83 (m, 2H), 3.30-3.18 (m, 2H), 2.90-2.79 (m, 2H), 2.38 (s, 3H), 2.38-2.30 (m, 2H), 2.30-2.21 (m, 2H), 2.18-2.03 (m, 2H), 1.57-1.50 (m, 2H), obscured by water).13CNMR (CDCl3, 100 MHz) δ: 162.54, 157.42 (d, J = 255.3 Hz), 147.74, 141.68 (d, J = 6.9 Hz), 140.30, 138.63 (d, J = 2.1 Hz), 137.98 (d, J = 28.2 Hz), 137.98, 130.38, 130.25, 129.59, 128.02, 125.66, 116.89, 115.36 (d, J = 2.7 Hz), 58.32, 56.82, 53.86, 52.20, 32.83, 21.37, 21.31. HRMS (ESI) m / z calc’d for C25H27FN6O [M+H]+: 447.23031; found: 447.22961. UPLC: rt: 3.47 min, purity: 93.23%. Example 18. 8-(2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1- yl)piperidin-1-yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine Attorney Docket No.103361-644WO1 Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1- yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 50% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a green solid (35 mg, 0.0714 mmol, 52% yield).1HNMR (CDCl3, 400 MHz, contaminated with DMSO) δ: 8.63 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 7.65 (s, 1H), 7.34 (d, J = 2.0 Hz, 1H), 7.29 (dd, J = 2.0, 8.3 Hz, 1H), 7.08 (d, J = 9.0 Hz, 1H), 6.90 (d, J = 8.3 Hz, 1H), 4.52 (tt, J = 4.2, 11.6 Hz, 1H), 4.28 (s, 4H), 4.09 (s, 3H), 3.45 (m, 2H), 3.26-3.19 (m, 2H), 2.86-2.80 (m, 2H), 2.35 (td, J = 2.0, 11.7 Hz, 2H), 2.28-2.20 (m, 2H), 2.08 (qd, J = 3.7, 12.0 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 162.61, 157.50 (d, J = 255.4 Hz), 147.43, 143.87 (d, J = 18.0 Hz), 141.76(d, J = 6.9 Hz), 140.39, 138.71 (d, J = 2.4 Hz), 138.21, 137.93, 130.40 (d, J = 12.9 Hz), 124.55, 119.12, 117.79, 116.67, 115.42 (d, J = 2.8 Hz), 114.81, 64.61, 64.54, 58.41, 56.92, 53.92, 52.29, 41.20, 32.93, 21.39. HRMS (ESI) m / z calc’d for C25H28FN6O2[M+H]+: 491.22014; found: 491.21942. UPLC: rt: 3.310 min, purity: 98.0%. Example 19. 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)- 1H-1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 6-(1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin- 3(4H)-one using General Procedure 3. Purification by flash chromatography (compound eluted in 100% ethyl acetate) and concentration in vacuo afforded the title compound as a white solid (18 mg, 0.0357 mmol, 39% yield).1HNMR (DMSO-d6, 400 MHz) δ: 10.81 (s, 1H), 8.79 (s, 1H), 8.55 (s, 1H), 8.29 (d, J = 9.0 Hz, 1H), 7.45 (d, J = 1.9 Hz, 1H), 7.31 (dd, J = 2.0, 8.3 Hz, 1H), 7.25 (d, J = 9.0 Hz, 1H), 7.00 (d, J = 8.3 Hz, 1H), 4.60 (s, 2H), 4.55-4.46 (m, 1H), 4.06 (s, 3H), 3.38-3.29 (m, 3H), 3.16-3.09 (m, 2H), 2.80-2.73 (m, 2H), 2.33-2.24 (m, 2H), 2.14-2.06 (m, 2H), 2.03-1.91 (m, 2H).13CNMR (DMSO-d6, 100 MHz, contaminated with chloroform) δ: 165.26, 162.52, 157.35 (d, J = 254.2 Hz), 146.10, 143.35, 141.42 (d, J = 6.9 Hz), 140.92, 138.61 (d, J = 1.9 Hz), 138.52, 138.24, 130.44, 130.31, 128.10, 125.87, 120.62, 119.54, 117.00, 115.82 (d, J = 2.4 Hz), 112.82, 67.25, 58.04, 56.70, 54.08, 51.96, 32.52, 21.33. HRMS (ESI) m / z calc’d for C26H27FN7O3[M+H]+: 504.21539; found: 504.21490. UPLC: rt: 3.05 min, purity: 95.87%. Example 20. 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)- 1H-1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one Attorney Docket No.103361-644WO1 Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 6-(1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin- 3(4H)-one using General Procedure 3. Purification by flash chromatography (compound eluted in 5% methanol in DCM) and concentration in vacuo afforded the title compound as a white solid (6 mg, 0.0119 mmol, 17% yield).1HNMR (DMSO-d6, 400 MHz) δ: 11.30 (s, 1H), 8.80 (s, 1H), 8.33 (s, 1H), 8.30 (d, J = 9.0 Hz, 1H), 7.57 (d, J = 8.2 Hz, 1H), 7.43 (d, J = 8.2 Hz, 1H), 7.26 (d, J = 9.0 Hz, 1H), 4.68 (s, 2H), 4.61-4.50 (m, 1H), 4.07 (s, 3H), 3.39-3.28 (m, obscured by water, 2H), 3.17-3.10 (m, 2H), 2.80-2.73 (m, 2H), 2.34-2.25 (m, 2H), 2.15-2.06 (m, 2H), 2.05-1.94 (m, 2H).13CNMR (DMSO-d6, 100 MHz) δ: 165.80, 162.05, 156.87 (d, J = 254.1 Hz), 146.21, 141.62 (d, J = 47.1 Hz), 140.94 (d, J = 7.1 Hz), 140.46, 138.51, 138.10 (d, J = 7.4 Hz), 137.78, 129.98, 129.85, 123.83, 120.54, 115.35 (d, J = 2.6 Hz), 115.04, 66.74, 57.64, 56.22, 53.61, 51.47, 31.96, 20.80. HRMS (ESI) m / z calc’d for C25H25FN8O3 [M+H]+: 505.21064; found: 505.20993. UPLC: rt: 3.021 min, purity: 98.1%. Example 21.8-(2-(4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 0.5% methanol in DCM) and concentration in vacuo afforded the title compound as a yellow solid (32 mg, 0.0638 mmol, 48% yield).1HNMR (CDCl3, 400 MHz) δ: 8.64 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 7.92 (d, J = 2.0 Hz, 1H), 7.77 (s, 1H), 7.67 (dd, J = 2.0, 8.3 Hz, 1H), 7.49 (d, J = 8.3 Hz, 1H), 7.09 (d, J = 9.0 Hz,1H), 4.55 (tt, J = 4.4, 11.8 Hz, 1H), 4.09 (3H), 3.46-3.39 (m, 2H), 3.27-3.19 (m, 2H), 2.88-2.80 (m, 2H), 2.35 (td, J = 1.8, 11.7 Hz, 2H), 2.29-2.21 (m, 2H), 2.08 (qd, J = 3.8, 12.1 Hz, 2H).13CNMR (CDCl3, 100 MHz) δ: 162.60, 157.50 (d, J = 255.2 Hz), 145.61, 141.74 (d, J = 6.9 Hz), 140.39, 138.70 (d, J = 2.1 Hz), 138.19, 137.91, 133.20, 132.05, 130.99, 130.92, 130.36 (d, J = 12.8 Hz), 127.58, 124.95, 117.70, 115.42 (d, J = 2.7 Hz), 58.67, 56.85, 53.90, 52.22, 32.91, 21.40. HRMS (ESI) m / z calc’d for C24H23Cl2FN6O [M+H]+: 501.13672; found: 501.13605. UPLC: rt: 3.82 min, purity: 99.21%. Attorney Docket No.103361-644WO1 tert-butyl 4-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine-1-carboxylate (27) Title compound was synthesized from tert-butyl 4-formylpiperidine-1-carboxylate and 2-oxo- 2-(p-tolyl)acetaldehyde using General Procedure 12. Purification by flash chromatography (compound eluted in 40% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as an orange solid (150 mg, 0.439 mmol, 29% yield).1HNMR (CDCl3, 400 MHz, contaminated with ethyl acetate) δ: 7.53 (d, J = 8.1 Hz, 2H), 7.17 (d, J = 7.9 Hz, 2H), 7.17 (s, 1H), 4.27-4.15 (m, 2H), 2.99 (tt, J = 3.7, 11.8 Hz, 1H), 2.92-2.80 (m, 2H), 2.35 (s, 3H), 2.09 (s, 1H), 2.07-2.00 (m, 2H, obscured by ethyl acetate), 1.71 (qd, J = 4.2, 12.1 Hz, 1H), 1.47 (s, 9H). 4-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine (28) Title compound was synthesized from tert-butyl 4-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine-1- carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a yellow solid. No purification or isolation attempted.

[0004] Attorney Docket No.103361-644WO1 Example 22Example 22. 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1- yl)ethyl)-1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(5-(p-tolyl)-1H-imidazol-2-yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 100% ethyl acetate) and concentration in vacuo afforded the title compound as a white solid (6 mg, 0.0135 mmol, 7% yield). Mixture of tautomers present in about a 65:35 ratio.1HNMR (CDCl3, 400 MHz, contaminated with ethyl acetate) δ: 8.90 (s, 0.3H), 8.79 (s, 0.6H), 8.62 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.65 (d, J = 7.7 Hz, 1.3H), 7.32 (d, J = 7.1 Hz, 0.6H), 7.21-7.14 (m, 2H), 7.08 (d, J = 9.0 Hz, 1H), 4.09 (s, 3H), 3.47-3.39 (m, 2H), 3.22-3.15 (m, 2H), 2.95-2.84 (m, 1H), 2.84-2.76 (m, 2H), 2.35 (s, 3H), 2.32-2.22 (m, 2H), 2.14-2.06 (m, 2H), 1.93-1.75 (m, 2H).13CNMR (CDCl3, 100 MHz) δ: 162.58, 157.45 (d, J = 255.3 Hz), 151.85, 141.80, 141.74, 140.29, 138.65 (d, J = 2.0 Hz), 138.16, 137.88, 136.55, 130.64, 130.51, 129.50, 124.77, 115.40 (d, J = 2.7 Hz), 57.37, 53.94, 53.39, 36.35, 31.42, 21.32, 21.11. HRMS (ESI) m / z calc’d for C26H28FN5O [M+H]+: 446.23507; found: 446.23474. UPLC: rt: 2.965 min, purity: 100%. Attorney Docket No.103361-644WO1 Pd(dppf)Cl2 tert-butyl 4-(4-(p-tolyl)-1H-pyrazol-1-yl)piperidine-1-carboxylate (30a) Title compound was synthesized from tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate and 1-bromo-4-methylbenzene using General Procedure 13. Purification by flash chromatography (compound eluted in 5% ethyl acetate in hexanes) and concentration in vacuo afforded a mixture of the title compound and the truncated pyrazole as a yellow oil (200 mg,0.387 mmol, 37% yield). tert-butyl 4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-1-yl)piperidine-1- carboxylate (30b) Title compound was synthesized from tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate and 6-bromo-2,3- dihydrobenzo[b][1,4]dioxine using General Procedure 13. Purification by flash chromatography (compound eluted in 10% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a clear oil (130 mg, 0.337 mmol, 32% yield).1HNMR (CDCl3, 400 MHz, contaminated with ethyl acetate and 6-bromo-2,3-dihydrobenzo[b][1,4]dioxine) δ: 7.68 (d, J = 0.6 Hz, 1H), 7.56 (d, J = 0.4 Hz, 1H), 6.97 (d, J = 2.0 Hz, 1H), 6.94 (dd, J = 2.1, 8.2 Hz, 1H), 6.85 (d, J = 8.3 Hz, 1H), 3.70 (s, 4H), 2.96-2.83 (m, 3H), 2.19-2.09 (m, 2H), 2.00- 1.87 (m, 3H), 1.48 (s, 9H). tert-butyl 4-(4-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazin-6-yl)-1H-pyrazol-1- yl)piperidine-1-carboxylate (30c) Attorney Docket No.103361-644WO1 Title compound was synthesized from tert-butyl 4-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan- 2-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate and 6-bromo-2H-benzo[b][1,4]oxazin-3(4H)- one using General Procedure 13. Purification by flash chromatography (compound eluted in 40% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a yellow oil (200 mg, 0.502 mmol, 33% yield).1HNMR (CDCl3, 400 MHz, contaminated with DCM and ethyl acetate) δ: 8.17 (s, 1H), 7.70 (s, 1H), 7.59 (s, 1H), 7.07 (dd, J = 2.0, 8.3 Hz, 1H), 6.97 (d, J = 8.3 Hz, 1H), 6.88 (d, J = 2.0 Hz, 1H), 4.63 (s, 2H), 4.33-4.21 (m, 3H), 2.97- 2.84 (m, 2H), 2.20-2.11 (m, 2H), 1.94 (1d, J = 4.4, 12.3 Hz, 2H), 1.48 (s, 9H). 4-(4-(p-tolyl)-1H-pyrazol-1-yl)piperidine (31a) Title compound was synthesized from tert-butyl 4-(4-(p-tolyl)-1H-pyrazol-1-yl)piperidine-1- carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a yellow oil. No purification or isolation attempted. 4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-1-yl)piperidine (31b) Title compound was synthesized from tert-butyl 4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)- 1H-pyrazol-1-yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compound as a yellow oil. No purification or isolation attempted. 6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (31c) Title compound was synthesized from tert-butyl 4-(4-(3-oxo-3,4-dihydro-2H- benzo[b][1,4]oxazin-6-yl)-1H-pyrazol-1-yl)piperidine-1-carboxylate using General Procedure Attorney Docket No.103361-644WO1 5. Concentration in vacuo afforded the title compound as a yellow solid. No purification or isolation attempted. Example 23. 7-fluoro-2-methoxy-8-(2-(4-(4-(p-tolyl)-1H-pyrazol-1-yl)piperidin-1- yl)ethyl)-1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(4-(p-tolyl)-1H-pyrazol-1-yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 40% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a yellow solid (3 mg, 0.00673 mmol, 3% yield). UPLC: rt: 3.70 min, purity: 80.84%. Example 24. 8-(2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-1-yl)piperidin- 1-yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-1-yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 60% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a off-white solid (17 mg, 0.0347 mmol, 24% yield).1HNMR (CDCl3, 400 MHz, contaminated with ethyl Attorney Docket No.103361-644WO1 acetate) δ: 8.62 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.67 (s, 1H), 7.57 (s, 1H), 7.07 (d, J = 9.0 Hz, 1H), 6.96 (d, J = 2.0 Hz, 1H), 6.92 (dd, J = 2.0, 8.2 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 4.26 (s, 4H), 4.21-4.10 (m, 1H), 4.08 (s, 3H), 3.46-3.39 (m, 2H), 3.25-3.18 (m, 2H), 2.85-2.78 (m, 2H), 2.36-2.26 (m, 2H), 2.23-2.14 (m, 2H), 2.11-1.98 (m, partially obscured by ethyl acetate, 2H).13CNMR (CDCl3, 100 MHz, contaminated with ethyl acetate) δ: 162.57, 157.46 (d, J = 255.2 Hz), 143.87, 142.37, 141.75 (d, J = 7.0 Hz), 140.33, 138.67 (d, J = 2.0 Hz), 138.187, 137.91, 136.15, 130.46 (d, J = 11.9 Hz), 126.57, 123.04, 122.48, 118.85, 117.73, 115.37 (d, J = 2.5 Hz), 114.39, 64.59, 64.54, 59.66, 56.94, 53.92, 52.49, 32.75, 21.32. HRMS (ESI) m / z calc’d for C27H28FN5O3[M+H]+: 490.22489; found: 490.22491. UPLC: rt: 3.449 min, purity: 97.7%. Example 25. 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)- 1H-pyrazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 6-(1-(piperidin-4-yl)-1H-pyrazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)- one using General Procedure 3. Purification by flash chromatography (compound eluted in ethyl acetate) and concentration in vacuo afforded the title compound as an off-white solid (4 mg, 0.00796 mmol, 5.5% yield).1HNMR (CDCl3, 400 MHz, contaminated with ethyl acetate) δ: 8.65 (s, 1H), 8.34 (s, 1H), 8.21 (d, J = 9.0 Hz, 1H), 7.71 (s, 1H), 7.63 (s, 1H), 7.11 (d, J = 8.1 Hz, 1H), 7.10 (dd, J = 2.0, 8.3 Hz, 1H), 6.99 (d, J = 8.3 Hz, 1H), 6.91 (d, J = 1.9 Hz, 1H), 4.65 (s, 2H), 4.26-4.17 (m, 1H), 4.12 (s, 3H), 3.52-3.42 (m, 2H), 3.32-3.21 (m, 2H), 2.92-2.82 (m, 2H), 2.42-2.29 (m, 2H), 2.29-2.18 (m, 2H), 2.16-2.04 (m, obscured by ethyl acetate, 2H).13CNMR (CDCl3, 100 MHz, contaminated with ethyl acetate) δ: 165.74, 162.62, 157.48 (d, J = 255.4 Hz), 142.38, 141.78, 141.70, 140.37, 138.71 (d, J = 1.1 Hz), 138.20, 137.92, 128.04, 126.59, 123.26, 121.92, 121.51, 117.41, 115.44, 112.98, 67.54, 59.78, 56.88, 53.95, 52.47, 32.75, 21.29. HRMS (ESI) m / z calc’d for C27H27FN6O3 [M+H]+: 503.22014; found: 503.21988. UPLC: rt: 3.175 min, purity: 92.29%. 7-fluoro-2-methoxy-8-vinyl-1,5-naphthyridine (33) Attorney Docket No.103361-644WO1 Title compound was synthesized from 8-bromo-7-fluoro-2-methoxy-1,5-naphthyridine using General Procedure 14. Purification by flash chromatography (compound eluted in 5% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a clear oil (700 mg, 3.43 mmol, 88% yield)(reaction run multiple times, with average yield of 80%).1HNMR (CDCl3, 400 MHz) δ: 8.66 (d, J = 2.4 Hz, 1H), 8.19 (d, J = 9.0 Hz, 1H), 7.57 (dd, J = 12.0, 18.2 Hz, 1H), 7.09 (d, J = 9.0 Hz, 1H), 6.61 (dd, J = 1.8, 18.2 Hz, 1H), 5.94 (dt, J = 1.7, 12.0 Hz, 1H), 4.10 (s, 3H). 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethane-1,2-diol (34) Title compound was synthesized from 7-fluoro-2-methoxy-8-vinyl-1,5-naphthyridine using General Procedure 15. Purification by flash chromatography (compound eluted in ethyl acetate) and concentration in vacuo afforded the title compound as a white solid (510 mg, 2.14 mmol, 60.7% yield) (reaction run multiple times, with average yield of 58%).1HNMR (CDCl3, 400 MHz) δ: 8.67 (d, J = 0.8 Hz, 1H), 8.26 (d, J = 9.2 Hz, 1H), 7.14 (d, J = 9.2 Hz, 1H), 5.47 (qd, J = 0.6, 4.2 Hz, 1H), 4.07 (s, 3H), 3.99 (dd, J = 7.6, 11.1 Hz, 1H), 3.89 (dd, J = 4.3, 11.0 Hz, 1H). orthoacetate 7-fluoro-2-methoxy-8-(oxiran-2-yl)-1,5-naphthyridine (35) Title compound was synthesized from 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethane- 1,2-diol using General Procedure 16. Purification by flash chromatography (compound eluted in 10% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (350 mg, 1.59 mmol, 60% yield) (reaction run multiple times, with average yield Attorney Docket No.103361-644WO1 of 60%).1HNMR (CDCl3, 400 MHz) δ: 8.63 (d, J = 2.0 Hz, 1H), 8.19 (d, J = 9.1 Hz, 1H), 7.11 (d, J = 9.0 Hz, 1H), 4.81 (dd, J = 2.8, 4.3 Hz, 1H), 4.10 (s, 3H), 3.60 (dd, J = 2.8, 5.7 Hz, 1H), 3.32 (ddd, J = 1.2, 4.4, 5.6 Hz, 1H). Example 26. 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-(4-(4-(p-tolyl)-1H-1,2,3- triazol-1-yl)piperidin-1-yl)ethan-1-ol Title compound was synthesized from 7-fluoro-2-methoxy-8-(oxiran-2-yl)-1,5-naphthyridine and 4-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)piperidine using General Procedure 17. Purification by flash chromatography (compound eluted in 1% methanol in DCM) and concentration in vacuo afforded the title compound plus the regioisomer in a 9:1 ratio as a white solid (7 mg, 0.0151 mmol, 22% yield).1HNMR ([CD3]2SO, 400 MHz, contaminated with DMSO) δ: 8.83 (d, J = 1.6 Hz, 0.1H), 8.80 (d, J = 1.7 Hz, 0.9H), 8.55 (s, 0.9H), 8.53 (s, 0.1H), 8.32 (d, J = 9.0 Hz, 0.1H), 8.31 (d, J = 9.0 Hz.0.9H), 7.70 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 9.1 Hz, 1H), 7.23 (d, J = 7.9 Hz, 2H), 6.05-5.97 (m, 1H), 5.59-5.51 (m, 1H), 4.52-4.41 (m, 1H), 4.07 (s, 0.3H), 4.04 (s, 2.7H), 3.27-3.19 (m, 1H), 3.01-2.90 (m, 3H), 2.40-2.25 (m, 5H), 2.10-1.96 (m, 2H), 1.96- 1.76 (m, 2H).13CNMR ([CD3]2SO, 100 MHz) δ: 161.79, 156.68 (d, J = 258.9 Hz), 146.11, 140.53, 139.94 (d, J = 7.4 Hz), 139.12, 138.84, 138.04 (d, J = 1.9 Hz), 136.96, 129.35, 128.11, 124.98, 119.13, 115.41 (d, J = 2.1 Hz), 63.08, 62.65, 57.37, 53.71, 52.40, 52.03, 31.96, 20.79. Attorney Docket No.103361-644WO1 HRMS (ESI) m / z calc’d for C25H27FN6O2 [M+H]+: 463.22523; found: 463.22467. UPLC: rt: 3.375 min, purity: 99.4%. Example 27. 2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1- yl)piperidin-1-yl)-1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol Title compound was synthesized from 7-fluoro-2-methoxy-8-(oxiran-2-yl)-1,5-naphthyridine and 4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)piperidine using General Procedure 17. Purification by flash chromatography (compound eluted in 75% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound plus the regioisomer in a 4:1 ratio as a white solid (7 mg, 0.0138 mmol, 7% yield).1HNMR ([CD3]2SO, 400 MHz) δ:8.82 (s, 0.2 H), 8.80 (s, 0.8 H), 8.49 (s, 0.8H), 8.48 (s, 0.2H), 8.31 (d, J = 9.0 Hz, 1H), 7.31-7.24 (m, 3H), 6.89 (d, J = 8.1 Hz, 1H), 6.04-5.96 (m, 1H), 5.58-5.51 (m, 1H), 4.51- 4.39 (m, 1H), 4.26 (s, 4H), 4.06 (s, 0.4H), 4.04 (s, 2.6H), 3.30-3.18 (m, obscured by water, 2H), 3.04-2.89 (m, 2H), 2.40-2.24 (m, 2H), 2.09-1.96 (m, 2H), 1.93-1.75 (m, 2H). HRMS (ESI) m / z calc’d for C26H27FN6O4 [M+H]+: 507.21506; found: 507.21448. UPLC: rt: 3.196 min, purity: 98.3%. Example 28. 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2- hydroxyethyl)piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one Title compound was synthesized from 7-fluoro-2-methoxy-8-(oxiran-2-yl)-1,5-naphthyridine and 6-(1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one using General Procedure 17. Purification by flash chromatography (compound eluted in 5% methanol in DCM) and concentration in vacuo afforded the title compound plus regioisomer in a 4:1 ratio as a white solid (5 mg, 0.00962 mmol, 19% yield).1HNMR ([CD3]2SO, 400 MHz, contaminated with DMSO) δ: 10.80 (s, 1H), 8.82 (d, J = 1.5 Hz, 0.2H), 8.79 (d, J = 1.7 Hz, 0.8H), 8.50 (s, 0.8H), 8.47 (s,0.2H), 8.32 (d, J = 9.0 Hz, 0.2H), 8.31 (d, J = 9.0 Hz, 0.8H), 7.43 (d, J = 2.0 Hz, 1H), 7.29 (dd, J = 2.0, 8.3 Hz, 1H), 7.26 (d, J = 9.1 Hz, 1H), 6.98 (d, J = 8.3 Hz, 1H), 6.00 (q, J = 6.5 Hz, 1H), 5.54 (d, J = 5.7 Hz, 1H), 4.75-4.70 (m, 0.2H), 4.59 (s, 2H), 4.50- 4.40 (m, 0.8H), 4.07 (s, 0.5H), 4.04 (s, 2.5H), 3.27-3.20 (m, 1H), 3.02-2.90 (m, 2H), 2.39-2.24 (m, 2H), 2.08-1.98 (m, 3H), 1.94-1.76 (m, 2H).13CNMR ([CD3]2SO, 100 MHz, contaminated with chloroform) δ: 164.75, 161.77, 156.66 (d, J = 258.8 Hz), 145.54, 142.83, 140.52, 139.94 (d, J = 7.3 Hz), 138.96 (d, J = 28.2 Hz), 138.03 (d, J = 2.1 Hz), 132.35 (d, J = 9.7 Hz), 127.58, 125.35, 120.11, 119.04, 116.48, 115.39 (d, J = 2.0 Hz), 112.30, 66.74, 63.08, 62.66, 57.43, Attorney Docket No.103361-644WO1 53.86, 53.69, 52.43, 52.02, 31.95 (d, J = 5.7 Hz). HRMS (ESI) m / z calc’d for C26H26FN7O4 [M+H]+: 520.21031; found: 520.21002. UPLC: rt: 2.948 min, purity: 98.8%. Example 29. 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2- hydroxyethyl)piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)- one Title compound was synthesized from 7-fluoro-2-methoxy-8-(oxiran-2-yl)-1,5-naphthyridine and 6-(1-(piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one using General Procedure 17. Precipitate was washed with DCM and collected to afford the title compound as a white solid (7 mg, 0.0134 mmol, 13% yield).1HNMR ([CD3]2SO, 400 MHz, contaminated with DMSO) δ: 11.29 (s, 1H), 8.80 (d, J = 1.3 Hz, 1H), 8.32 (d, J = 9.0 Hz, 1H), 8.28 (s, 1H), 7.55 (d, J = 8.2 Hz, 1H), 7.42 (d, J = 8.2 Hz, 1H), 7.27 (d, J = 9.1 Hz, 1H), 6.01 (q, J = 6.0 Hz, 1H), 5.55 (d, J = 5.6 Hz, 1H), 4.67 (s, 2H), 4.56-4.46 (m, 1H), 4.04 (s, 3H), 3.26- 3.18 (m, 1H), 3.034-2.95 (m, 2H), 2.92 (dd, J = 6.4, 12.5 Hz, 1H), 2.40-2.25 (m, 2H), 2.10- 1.98 (m, 2H), 1.96-1.79 (m, 2H).13CNMR ([CD3]2SO, 100 MHz) δ: 165.78, 161.79, 156.67 (d, J = 259.6), 146.15, 141.83, 141.35, 140.54, 139.95 (d, J = 7.4 Hz), 139.13, 138.85, 138.50, 138.03 (d, J = 2.2 Hz), 132.37 (d, J = 9.6 Hz), 123.82, 120.55, 115.41, 115.02, 66.74, 63.13, 62.65, 57.50, 53.71, 52.37, 52.06, 31.91 (d, J = 8.4 Hz). HRMS (ESI) m / z calc’d for C25H25FN8O4 [M+H]+: 521.20556; found: 521.20508. UPLC: rt: 2.890 min, purity: 98.4%. Example 30. 2-(4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)-1-(3- fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol Title compound was synthesized from 7-fluoro-2-methoxy-8-(oxiran-2-yl)-1,5-naphthyridine and 4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)piperidine using General Procedure 17. Purification by flash chromatography (compound eluted in 2% methanol in DCM) and concentration in vacuo afforded the title compound plus the regioisomer in a 9:1 ratio as a white solid (7 mg, 0.0135 mmol, 19.8% yield).1HNMR ([CD3]2SO, 400 MHz, contaminated with DMSO) δ: 8.82 (d, J = 1.6 Hz, 0.1H), 8.79 (d, J = 1.8 Hz, 0.9H), 8.77 (s, 0.9H), 8.76 (s, 0.1H), 8.32 (d, J = 9.0 Hz, 0.1H), 8.31 (d, J = 9.0 Hz, 0.9H), 8.05 (d, J = 2.0 Hz, 1H), 7.82 (dd, J = 2.0, 8.4 Hz, 1H), 7.70 (d, J = 8.4 Hz, 1H), 7.26 (d, J = 9.1 Hz, 1H), 6.00 (q, J = 6.3 Hz, 1H), 5.55 (d, J = 5.7 Hz, 1H), 4.75-4.71 (m, 0.1H), 4.54-4.44 (m, 0.9H), 4.07 (s, 0.4H), 4.04 (s, 2.6 H), 3.26-3.19 (m, 1H), 3.02-2.91 (m, 3H), 2.41-2.27 (m, 2H), 2.11-2.00 (m, 2H), 1.91-1.74 (m, Attorney Docket No.103361-644WO1 2H). HRMS (ESI) m / z calc’d for C24H23Cl2FN6O2 [M+H]+: 517.13163; found: 517.13080. UPLC: rt: 3.722 min, purity: 99.5%. 7-fluoro-8-(2-(4-iodopiperidin-1-yl)ethyl)-2-methoxy-1,5-naphthyridine (37) Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-iodopiperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 15% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a clear oil (130 mg, 0.313 mmol, 31% yield).1HNMR (CDCl3, 400 MHz, contaminated with DCM) δ: 8.61 (s, 1H), 8.17 (d, J = 9.0 Hz, 1H), 7.07 (d, J = 9.0 Hz, 1H), 4.37-4.26 (m, 1H), 4.08 (s, 3H), 3.42-3.33 (m, 2H), 2.84-2.70 (m, 4H), 2.46-2.36 (m, 2H), 2.21-2.09 (m, 4H). 8-(2-(4-azidopiperidin-1-yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine (38) Title compound was synthesized from 7-fluoro-8-(2-(4-iodopiperidin-1-yl)ethyl)-2-methoxy- 1,5-naphthyridine using General Procedure 18. Concentration in vacuo afforded the title compound as a yellow oil (100 mg, 0.303 mmol, 96.7% yield).1HNMR (CDCl3, 400 MHz) δ: 8.62 (s, 1H), 8.18 (d, J = 9.0 Hz, 1H), 7.08 (d, J = 9.0 Hz, 1H), 4.08 (s, 3H), 3.47-3.34 (m, 3H), Attorney Docket No.103361-644WO1 2.98-2.87 (m, 2H), 2.79-2.70 (m, 2H), 2.39-2.27 (m, 2H), 1.98-1.87 (m, 2H), 1.75-1.62 (m, 2H). Example 31 Example 31. 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)- 1H-1,2,3-triazol-4-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one Title compound was synthesized from 8-(2-(4-azidopiperidin-1-yl)ethyl)-7-fluoro-2-methoxy- 1,5-naphthyridine and 6-ethynyl-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one using General Procedure 19, method A. Purification by flash chromatography on a neutral column (compound eluted in 1% methanol in DCM) and concentration in vacuo afforded the title compound as an orange solid (12 mg, 0.0237 mmol, 15.7% yield).1HNMR ([CD3]2SO, 400 MHz) δ: 11.72 (s, 1H), 8.80 (s, 1H), 8.46 (s, 1H), 8.32 (s, 1H), 8.30 (d, J = 9.0 Hz, 1H), 7.26 (d, J = 9.0 Hz, 1H), 4.92 (s, 2H), 4.63-4.52 (m, 1H), 4.07 (s, 3H), 3.40-3.31 (m, obscured by water, 2H), 3.17-3.10 (m, 2H), 2.81-2.72 (m, 2H), 2.35-2.24 (m, 2H), 2.16-2.07 (m, 2H), 2.07-1.94 (m, 2H).13CNMR ([CD3]2SO, 100 MHz) δ: 165.15, 162.04, 156.88 (d, J = 258.2 Hz), 146.55, 143.92, 140.93 (d, J = 7.2 Hz), 140.45, 138.12, 138.05, 137.78, 137.15 (d, J = 11.7 Hz), 130.92, 129.89 (d, J = 13.1 Hz), 121.08, 115.35, 67.24, 57.74, 56.20, 53.60, 51.45, 31.94, 20.80. HRMS (ESI) m / z calc’d for C24H24FN9O3[M+H]+: 506.20589; found: 506.20493. UPLC: rt: 2.82 min, purity: 95.72%. Attorney Docket No.103361-644WO1 8-(2-((2r,5r)-5-azido-1,3-dioxan-2-yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine (41) Title compound was synthesized from (2r,5r)-2-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)ethyl)-1,3-dioxan-5-amine and sulfurazidic fluoride using General Procedure 20 to afford the title compound as a white solid (133 mg, 0.4 mmol, 51% yield). The reaction was repeated multiple times with an average yield of 49.7% (ranges from 38-60%).1HNMR (CDCl3, 400 MHz) δ: 8.61 (d, J = 0.4 Hz, 1H), 8.17 (d, J = 9.0 Hz, 1H), 7.06 (d, J = 9.0 Hz, 1H), 4.46 (t, J = 5.0 Hz, 1H), 4.24-4.17 (m, 2 H), 3.73-3.62 (m, 1H), 3.45-3.37 (m, 2H), 2.62 (td, J = 8.0, 1.3 Hz, 2H), 2.08 (td, J = 7.7, 5.0 Hz, 2H).13C NMR (100 MHz, CDCl3) δ: 162.35, 157.06 (d, J = 255.4 Hz), 141.51 (d, J = 6.7 Hz), 140.14, 138.51, 137.89 (d, J = 28.1 Hz), 131.38 (d, J = 12.6 Hz), 115.15, 101.57, 69.10, 53.74 (d, J = 4.2) Attorney Docket No.103361-644WO1 Example 32. 7-fluoro-2-methoxy-8-(2-((2r,5r)-5-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)-1,3- dioxan-2-yl)ethyl)-1,5-naphthyridine Title compound was synthesized from 8-(2-((2r,5r)-5-azido-1,3-dioxan-2-yl)ethyl)-7-fluoro-2- methoxy-1,5-naphthyridine and 1-ethynyl-4-methylbenzene using General Procedure 19, method B. Purification by flash chromatography (compound eluted in 25% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (20 mg, 0.0445 mmol, 59% yield).1HNMR (CDCl3, 400 MHz) δ: 8.63 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 7.73-7.64 (m, 2H), 7.24 (d, J = 8.0 Hz), 7.08 (d, J = 9.0 Hz), 4.84-4.73 (m, 1H), 4.71 (t, 1H), 4.45 (dd, J = 11, 4.6 Hz), 4.14 (t, 2 H), 4.10 (s, 3H), 3.35 (t, 2H), 2.38 (s, 3H), 2.24-2.11 (m, 2H).13CNMR (CDCl3, 400 MHz) 162.40, 157.09 (J =255.6 Hz), 147.68, 141.52 (d, J = 6.9 Hz), 140.18, 138.55 (d, J =1.9 Hz), 138.32, 137.93 (d, J = 28.2 Hz), 131.29 (d, J = 12.8 Hz), 129.58, 127.29, 125.67, 118.70, 115.24 (d, J = 2.5 Hz), 101.99, 69.37, 53.80, 52.57, 33.12, 21.29, 18.14 (d, J = 1.8 Hz). HRMS (ESI) m / z calc’d C24H24FN5O3: 450.19359 found: 450.19320. UPLC: rt: 5.197, purity: 99.4% Example 33. 8-(2-((2r,5r)-5-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1- yl)-1,3-dioxan-2-yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine Title compound was synthesized from 8-(2-((2r,5r)-5-azido-1,3-dioxan-2-yl)ethyl)-7-fluoro-2- methoxy-1,5-naphthyridine and 6-ethynyl-2,3-dihydrobenzo[b][1,4]dioxine using General Procedure 19, method B. Purification by flash chromatography (compound eluted in 50% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (21 mg, 0.0426 mmol, 42.8% yield).1HNMR ([CD3]2SO, 400 MHz) δ: 8.78 (s, 1H), 8.54 (s, 1H), 8.28 d, J = 9.0 Hz, 1H), 7.30-7.22 (m, 3H), 6.91 (d, J = 8.4 Hz, 1H), 4.87-4.80 (m, 1H), 4.78 (t, 1H), 4.41 (m, 2H), 4.26 (s, 1H), 4.08-4.00 (m, 2H), 4.06 (s, 3H), 3.26 (t, 2H), 2.10-2.00 (m, 2H).13CNMR ([CD3]2SO, 100 MHz) δ: 162.48, 157.10 (d, J = 254.5 Hz), 146.23, 144.12, 143.80, 141.28 (d, J = 6.7 Hz), 139.76 (d, J = 232.4 Hz), 138.33, 131.15 (d, J = 12.6 Hz), 124.30, 120.80, 118.72, 118.03, 115.78 (d, J = 2.3 Hz), 114.20, 101.33, 68.81, 64.60, 54.04, 52.13, 33.28, 29.79, 18.23. HRMS (ESI) m / z calc’d for C25H25FN5O5 [M+H]+: 494.18342; found: 494.18325. UPLC: rt: 4.902 min, purity: 100%. Example 34. 6-(1-((2r,5r)-2-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)-1,3- dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one Attorney Docket No.103361-644WO1 Title compound was synthesized from 8-(2-((2r,5r)-5-azido-1,3-dioxan-2-yl)ethyl)-7-fluoro-2- methoxy-1,5-naphthyridine and 6-ethynyl-2H-benzo[b][1,4]oxazin-3(4H)-one using General Procedure 19, method B. Purification by flash chromatography (compound eluted in ethyl acetate) and concentration in vacuo afforded the title compound as a white solid (15 mg, 0.0296 mmol, 33% yield).1HNMR ([CD3]2SO, 400 MHz) δ: 10.81 (s, 1H), 8.79 (s, 1H), 8.54 (s, 1H), 8.30 (d, J = 9.0, 1H), 7.42 (d, J = 1.9, 1H), 7.30 (dd, J = 8.3, 1.9 Hz, 1H), 7.26 (d, J = 9.0, 1H), 7.02 (d, J = 8.3), 4.89-4.81 (m, 1H), 4.79 (t, 1H), 4.60 (s, 2H), 4.42 (dd, J = 11, 4.8 Hz, 2H), 4.07 (s, 3H), 4.10-4.02 (m, 1H), 3.32-3.24 (m, 2H), 2.10-2.02 (m, 2H).13CNMR ([CD3]2SO, 100 MHz) δ: 165.23, 162.49, 157.10 (d, J = 254.6 Hz), 146.00, 143.52, 141.29 (d, J = 6.9 Hz), 140.93, 139.77 (d, J = 231.9 Hz), 138.34, 131.16 (d, J = 12.7 Hz), 128.18, 125.35, 120.99, 120.62, 117.12, 115.49 (d, J = 2.3 Hz), 112.87, 101.30, 68.79, 67.24, 54.05, 52.18, 33.29, 18.23. HRMS (ESI) m / z calc’d for C25H24FN6O5 [M+H]+: 507.17867; found: 507.18990. UPLC: rt: 4.439 min, purity: 97.4%. Example 35. 8-(2-((2r,5r)-5-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2- yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine Title compound was synthesized from 8-(2-((2r,5r)-5-azido-1,3-dioxan-2-yl)ethyl)-7-fluoro-2- methoxy-1,5-naphthyridine and 1,2-dichloro-4-ethynylbenzene using General Procedure 19, method B. Purification by flash chromatography (compound eluted in 50% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (20 mg, 0.0397 mmol, 66% yield).1HNMR (CDCl3, 400 MHz) δ: 8.63 (s, 1H), 8.19 (d, J = 9.0 Hz, 1H), 7.91 (d, J = 1.6 Hz, 1H), 7.75 (s, 1H), 7.65 (dd, J = 8.3, 1.7 Hz), 7.50 (d, J = 8.3 Hz) 7.09 (d, J = 9.0 Hz, 1H), 4.84-4.74 (m,1H), 4.71 (t, 1H), 4.45 (dd, J = 11.1, 4.7 Hz, 2H), 4.14 (t, 2H), 4.11 (s, 3H), 3.35 (t, 2H), 2.24-2.13 (m, 2H).13CNMR (CDCl3, 100 MHz) δ: 162.42, 157.08 (J =255.4 Hz), 145.49, 141.51 (J = 6.7 Hz), 140.20, 138.57 (d, J = 2.0 Hz), 137.93 (d, J = 28.2 Hz), 131.23 (d, J = 141.4 Hz), 131.22 (d, J = 12.7 Hz), 130.94, 127.55, 124.90, 119.50, 115.26 (d, J = 2.7 Hz), 102.04, 69.25, 53.79, 52.76, 33.05, 29.70, 18.12 (d, J = 1.9 Hz). HRMS (ESI) m / z calc’d for C23H20Cl2FN5O3 [M+H]+: 504.10000; found: 504.09958. UPLC: rt: 5.682 min, purity: 100%. Attorney Docket No.103361-644WO1 (S)-1-((2r,5S)-5-azido-1,3-dioxan-2-yl)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)ethan-1-ol (43) Title compound was synthesized from (S)-1-((2r,5S)-5-amino-1,3-dioxan-2-yl)-2-(3-fluoro-6- methoxy-1,5-naphthyridin-4-yl)ethan-1-ol and sulfurazidic fluoride using General Procedure 20 to afford the title compound as a white solid (83 mg, 0.24 mmol, 78% yield). Reaction was repeated multiple times with an average yield of 62% (range 52.9-78.4%).1HNMR (CDCl3, 400 MHz) δ: 8.66 (s, 1H), 8.21 (d, J = 9.0 Hz, 1H), 7.09 (d, J = 9.0 Hz, 1H), 4.46 (d, J = 4.1 Hz, 1H), 4.35-4.24 (m, 3H), 4.10-4.03 (m, 1H), 4.08 (s, 3H), 3.80-3.69 (m, 1H), 3.55-3.36 (m, Attorney Docket No.103361-644WO1 Example 36. (S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-((2r,5S)-5-(4-(p-tolyl)- 1H-1,2,3-triazol-1-yl)-1,3-dioxan-2-yl)ethan-1-ol Title compound was synthesized from (S)-1-((2r,5S)-5-azido-1,3-dioxan-2-yl)-2-(3-fluoro-6- methoxy-1,5-naphthyridin-4-yl)ethan-1-ol and 1-ethynyl-4-methylbenzene using General Procedure 19, method B. Purification by flash chromatography (compound eluted in 80% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (30 mg, 0.0644 mmol, 83% yield).1HNMR (CDCl3, 400 MHz) δ: 8.69 (s, 1H), 8.23 (d, J = 9.0 Hz, 1H), 7.72-7.68 (m, 3H), 7.24 (m, 2H), 7.11 (d, J = 9.0 Hz, 1H), 4.89-4.79 (m, 1H), 4.70 (d, J = 4.2 Hz), 4.58-4.49 (m, 2H), 4.46 (d, J = 4.9 Hz, 1H), 4.26-4.14 (m, 3H), 4.11 (s, 3H), 3.59 (dd, J = 13.7, 1.3 Hz, 1H), 3.48 (dd, J = 13.5, 1.2 Hz), 2.38 (s, 3H).13CNMR (CDCl3, 100 MHz) δ: 163.03, 157.47 (d, J = 257.2 Hz), 147.74, 141.92 (d, J = 5.8 Hz), 140.90, 138.60 (d, J = 2.8 Hz), 138.37, 138.34 (d, J = 28.5 Hz), 129.59, 128.40 (d, J = 12.5 Hz), 127.23, 125.69, 118.71, 115.58 (d, J = 2.5 Hz), 102.51, 71.98, 69.37 (d, J = 8.4 Hz), 54.24, 52.53, 26.00 (d, J = 2.1 Hz), 21.29. HRMS (ESI) m / z calc’d for C24H24FN5O4 [M+H]+: 466.18851; found: 466.18848. UPLC: rt: 4.573 min, purity: 97.6%. Example 37. (S)-1-((2r,5S)-5-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1- yl)-1,3-dioxan-2-yl)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol Title compound was synthesized from (S)-1-((2r,5S)-5-azido-1,3-dioxan-2-yl)-2-(3-fluoro-6- methoxy-1,5-naphthyridin-4-yl)ethan-1-ol and 6-ethynyl-2,3-dihydrobenzo[b][1,4]dioxine using General Procedure 19, method B. Purification by flash chromatography (compound eluted in 85% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (28 mg, 0.055 mmol, 48% yield).1HNMR (CDCl3, 400 MHz) δ: 8.68 (s, 1H), 8.23 (d, J = 9.0 Hz, 1H), 7.62 (s, 1H), 7.31 (dd, J = 16.2, 2.0 Hz, 2H), 7.11 (d, J = 9.0 Hz, 1H), 6.91 (d, J = 8.3 Hz, 1H), 4.87-4.77 (m, 1H), 4.69 (d, J = 4.1 Hz, 1H), 4.58-4.48 (m, 2H), 4.45 (d, J = 4.9 Hz, 1H), 4.29 (s, 4H), 4.22 (dd, J = 11.0, 2.2 Hz, 1H), 4.19-4.13 (m, 1H), 4.119s, 3H), 3.59 (ddd, J = 13.8, 3.6, 1.2 Hz, 1H), 3.52-3.44 (m, 1H).13CNMR (CDCl3, 100 MHz) δ: 163.02, 157.48 (d, J = 257.0 Hz), 147.33, 143.90 (d, J = 5.9 Hz), 141.92 (d, J = 5.9 Hz), 140.88, 138.59 (d, J = 2.1 Hz), 138.33 (d, J = 28.5 Hz), 128.41 (d, J = 12.8 Hz), 123.62, 119.06, 118.49, 117.74, 115.58 (d, J = 2.6 Hz), 114.78, 102.50, 71.98, 69.36 (d, J = 8.2 Hz), 64.41 (d, J = 8.0 Hz), 54.24, 52.51, 25.98. HRMS (ESI) m / z calc’d for C25H24FN5O6[M+H]+: 510.17834; found: 510.17896. UPLC: rt: 4.292 min, purity: 98.1%. Attorney Docket No.103361-644WO1 Example 38. 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1- hydroxyethyl)-1,3-dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one Title compound was synthesized from (S)-1-((2r,5S)-5-azido-1,3-dioxan-2-yl)-2-(3-fluoro-6- methoxy-1,5-naphthyridin-4-yl)ethan-1-ol and 6-ethynyl-2H-benzo[b][1,4]oxazin-3(4H)-one using General Procedure 19, method B. Purification by flash chromatography (compound eluted in 2% methanol in DCM) and concentration in vacuo afforded the title compound as a white solid (20 mg, 0.0383 mmol, 61% yield).1HNMR ([CD3]2SO, 400 MHz) δ: 10.82 (s, 1H), 8.76 (s, 1H), 8.57 (s, 1H), 8.28 (d, J = 9.0 Hz, 1H), 7.43 (d, J = 1.9 Hz, 1H), 7.31 (dd, J = 8.3, 1.9 Hz, 1H), 7.23 (d, J = 9.0 Hz, 1H), 7.02 (d, J = 8.3 Hz, 1H), 5.06 (d, J = 6.0 Hz, 1H), 4.94- 4.81 (m, 1H), 4.60 (s, 2H), 4.51-4.45 (m, 2H), 4.18-4.02 (m, 3H), 4.05 (s, 3H), 3.50-3.40 (m, 1H), 3.22 (dd, J = 12.4, 9.5 Hz, 1H).13CNMR ([CD3]2SO, 100 MHz) δ: 165.23, 162.25, 157.94 (d, J = 254.9 Hz), 146.02, 143.53, 141.70 (d, J = 6.6 Hz), 140.88, 138.45 (d, J = 1.8 Hz), 138.42 (d, J= 28.3 Hz), 129.44 (d, J = 12.7 Hz), 128.19, 125.36, 121.02, 120.63, 117.13, 115.53 (d, J = 1.7 Hz), 112.88, 103.43, 70.23, 68.79 (d, J = 3.7 Hz), 67.24, 54.08, 52.32, 26.65. HRMS (ESI) m / z calc’d for C25H23FN6O6 [M+H]+: 523.17359; found: 523.17303. UPLC: rt: 3.866 min, purity: 95.9%. Example 39. 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1- hydroxyethyl)-1,3-dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin- 3(4H)-one Title compound was synthesized from (S)-1-((2r,5S)-5-azido-1,3-dioxan-2-yl)-2-(3-fluoro-6- methoxy-1,5-naphthyridin-4-yl)ethan-1-ol and 6-ethynyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)- one using General Procedure 19, method B. Precipitate collected as the title compound as a orange-yellow solid (55 mg, 0.105 mmol, 100% yield).1HNMR ([CD3]2SO, 400 MHz) δ: 11.33 (s, 1H), 8.77 (s, 1H), 8.42 (s, 1H), 8.29 (d, J = 9.0 Hz, 1H), 7.59 (d, J = 8.1 Hz, 1H), 7.44 (d, J = 8.2 Hz, 1H), 7.24 (d, J = 9.0 Hz, 1H), 5.04 (d, J = 6.0 Hz, 1H), 5.02-4.92 (m, 1H), 4.73 (d, J = 4.2 Hz, 1H), 4.68 (s, 2H), 4.51-4.43 (m, 2H), 4.20-4.09 (m, 3H), 3.49-3.41 (m, 1H), (dd, J = 12.6, 9.8 Hz, 1H). HRMS (ESI) m / z calc’d for C24H22FN7O6 [M+H]+: 524.16884; found: 524.16888. UPLC: rt: 3.807 min, purity: 93.6%. Example 40. (S)-1-((2r,5S)-5-(4-(5,6-dichloropyrazin-2-yl)-1H-1,2,3-triazol-1-yl)-1,3- dioxan-2-yl)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol Attorney Docket No.103361-644WO1 Title compound was synthesized from (S)-1-((2r,5S)-5-azido-1,3-dioxan-2-yl)-2-(3-fluoro-6- methoxy-1,5-naphthyridin-4-yl)ethan-1-ol and 1,2-dichloro-4-ethynylbenzene using General Procedure 19, method B. Purification by flash chromatography (compound eluted in 65% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (35 mg, 0.0673 mmol, 87% yield).1HNMR ([CD3]2SO, 400 MHz) δ: 8.82 (s, 1H), 8.76 (s, 1H), 8.27 (d, J = 9.0 Hz, 1H), 8.05 (d, J = 1.9 Hz, 1H), 7.82 (dd, J = 8.4, 1.9 Hz, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.23 (d, J = 9.0 Hz, 1H), 5.07 (d, J = 6.0 Hz, 1H), 4.96-4.83 (m, 1H), 4.70 (d, J = 4.2 Hz, 1H), 4.56-4.44 (m, 2H), 4.18-4.01 (m, 3H), 4.05 (s, 3H), 3.49-3.40 (m, 1H), 3.22 (dd, J = 12.5, 9.5 Hz).13CNMR ([CD3]2SO, 100 MHz) δ: 162.25, 157.93 (d, J = 254.9 Hz), 144.33, 141.69 (d, J = 6.7 Hz), 140.87, 138.45 (d, J = 1.9 Hz), 138.41 (d, J = 28.3 Hz), 132.26, 131.60, 130.78, 129.41 (d, J = 12.6 Hz), 127.19, 125.63, 122.60, 115.52 (d, J = 2.0 Hz), 103.46, 70.20, 68.72 (d, J = 3.5 Hz), 54.08, 52.41, 26.65. HRMS (ESI) m / z calc’d for C23H20Cl2FN5O4 [M+H]+: 520.09491; found: 520.09509. UPLC: rt: 5.064 min, purity: 98.3%. Example 41. 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1- hydroxyethyl)-1,3-dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrazino[2,3-b][1,4]oxazin- 3(4H)-one Title compound was synthesized from (S)-1-((2r,5S)-5-azido-1,3-dioxan-2-yl)-2-(3-fluoro-6- methoxy-1,5-naphthyridin-4-yl)ethan-1-ol and 6-ethynyl-2H-pyrazino[2,3-b][1,4]oxazin- 3(4H)-one using General Procedure 19, method B. Precipitate was washed with DCM and methanol to afford the title compound as a brown solid (50 mg, 0.0953 mmol, 83% yield). HRMS (ESI) m / z calc’d for C23H21FN8O6 [M+H]+: 525.16409; found: 525.16400. UPLC: rt: 3.614 min, purity: 89.2%. Attorney Docket No.103361-644WO1 (E)-2-(4-methylbenzylidene)quinuclidin-3-one (45a) Title compound was synthesized from quinuclidin-3-one and 4-methylbenzaldehyde using General Procedure 21. Purification by flash chromatography (compound eluted in 5% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a yellow solid (125 mg, 0.550 mmol, 59% yield).1HNMR CDCl3, 400 MHz) δ: 7.93 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.1 Hz, 2H), 7.00 (s, 1H), 3.15 (m, 2H), 2.98 (m, 2H), 2.62 (m, 1H), 2.36 (s, 3H), 2.02 (td, J = 8.9, 4.1 Hz, 4H). (E)-2-((2,3-dihydrobenzo[b][1,4]dioxin-6-yl)methylene)quinuclidin-3-one (45b) Title compound was synthesized from quinuclidin-3-one and 2,3- dihydrobenzo[b][1,4]dioxine-6-carbaldehyde using General Procedure 21. Purification by flash chromatography (compound eluted in 10% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a yellow solid (225 mg, 0.829 mmol, 15% yield).1HNMR CDCl3, 400 MHz) δ: 7.87 (d, J = 2.1 Hz), 1H), 7.41 (dd, J = 8.5, 2.0 Hz, 1H), 6.90 (s, 1H), 6.38 (d, J = 8.4 Hz, 1H), 4.27 (m, 4H), 3.13 (m, 2H), 2.95 (m, 2H), 2.60 (q, J = 3.0 Hz, 1H), 2.00 (tt, J = 8.2, 3.1 Hz, 4H). 4-(5-(p-tolyl)-1H-pyrazol-3-yl)piperidine (46a) Title compound was synthesized from (E)-2-(4-methylbenzylidene)quinuclidin-3-one using General Procedure 22. Purification by flash chromatography (compound eluted in 2.5% methanol in DCM) and concentration in vacuo afforded the title compound as a clear oil (24 mg, 0.101 mmol, 18% yield).1HNMR CD3OD, 400 MHz) δ: 7.62 (d, J = 8.0 Hz, 2H), 7.22 Attorney Docket No.103361-644WO1 (d, J = 7.9 Hz), 6.42 (s, 1H), 4.86 (s, 2H), 3.13 (m, 2H), 2.84 (tt, J = 11.9, 3.7 Hz, 1H), 2.74 (td, J = 12.2, 2.7 Hz, 2H), 2.36 (s, 3H), 1.98 (d, J = 13.6 Hz, 2H), 1.69 (qd, J = 12.5, 4.1 Hz, 2H). 4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-3-yl)piperidine (46b) Title compound was synthesized from (E)-2-((2,3-dihydrobenzo[b][1,4]dioxin-6- yl)methylene)quinuclidin-3-one using General Procedure 22. Purification by flash chromatography (compound eluted in 10% methanol in DCM) and concentration in vacuo afforded the title compound as a clear oil (25 mg, 0.0876 mmol, 11% yield).1HNMR CD3OD, 400 MHz) δ: 7.20 (m, 2H), 6.86 (d, J = 8.4 Hz, 1H), 6.36 (s, 1H), 4.27 (s, 4H), 3.15 (m, 2H), 2.84 (tt, J = 11.9, 3.8 Hz, 1H), 2.75 (td, J = 12.3, 3.3 Hz, 2H), 1.99 (d, J = 11.2 Hz, 2H), 1.70 (qd, J = 12.6, 3.8 Hz, 2H). Example 42. 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-pyrazol-3-yl)piperidin-1- yl)ethyl)-1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(5-(p-tolyl)-1H-pyrazol-3-yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in 80% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a clear oil (47 mg, 0.105 mmol, 39% Attorney Docket No.103361-644WO1 yield).1HNMR CDCl3, 400 MHz) δ: 8.62 (s, 1H), 8.18 (d, J = 9.1 Hz, 1H), 7.56 (br s, 2H), 7.21 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 1H), 6.36 (s, 1H), 4.11 (s, 3H), 3.47 (m, 2H), 3.22 (m, 2H), 2.83 (m, 2H), 2.37 (s, 3H), 2.30 (m, 1H), 2.03 (m, 2H).1.88 (m, 2H). Example 43. 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-3-yl)piperidin- 1-yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine Title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-3-yl)piperidine using General Procedure 3. Purification by flash chromatography (compound eluted in ethyl acetate) and concentration in vacuo afforded the title compound as a white solid (3 mg, 0.00613 mmol, 7% yield).1HNMR DMSO-d6, 400 MHz) δ: 12.66 (s, 0.25H), 12.44 (s, 0.55H), 8.78 (s, 1H), 8.28 (d, J = 9.0 Hz, 1H), 7.24 (d, J = 9.4 Hz, 2H), 7.21 (d, J = 1.9 Hz, 1H), 6.83 (d, J = 7.0 Hz, 1H), 6.35 (s, 1H), 4.24 (s, 4H), 4.05 (s, 3H), 3.35 (m, 1H), 3.28 (s, 2H), 3.06 (d, J = 10.8 Hz, 2H), 2.71 (t, J = 7.3 Hz, 2H), 2.15 (t, J = 11.4 Hz, 2H), 1.88 (d, J = 12.0 Hz, 2H), 1.59 (m, 2H). tert-butyl (E)-4-(3-hydroxy-3-(p-tolyl)acryloyl)piperidine-1-carboxylate (48) Title compound was synthesized from 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid and 1-(p-tolyl)ethan-1-one using General Procedure 23. Purification by flash chromatography (compound eluted in 10% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a yellow oil (165 mg, 0.478 mmol, 48% yield).1HNMR CDCl3, 400 MHz) δ: 7.74 (d, J = 8.3 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 6.12 (s, 1H), 4.15 (d, J = 13.2 Hz, 2H), 2.75 (m, 2H), 2.42 (tt, J = 8.0, 3.7 Hz, 1H), 2.37 (s, 3H), 1.84 (d, J = 10.8 Hz, 2H), 1.62 (qd, J = 12.2, 4.3 Hz, 2H), 1.43 (s, 9H). Attorney Docket No.103361-644WO1 tert-butyl 4-(1-methyl-5-(p-tolyl)-1H-pyrazol-3-yl)piperidine-1-carboxylate and tert- butyl 4-(1-methyl-3-(p-tolyl)-1H-pyrazol-5-yl)piperidine-1-carboxylate (49) The title compounds were synthesized as a mixture of isomers from tert-butyl (E)-4-(3- hydroxy-3-(p-tolyl)acryloyl)piperidine-1-carboxylate using General Procedure 24. The isomers were separated by flash chromatography (ethyl acetate in hexanes) and then concentrated in vacuo to afford clear oils. The regiochemistry of each isomer was not assigned. 4-(1-methyl-5-(p-tolyl)-1H-pyrazol-3-yl)piperidine and 4-(1-methyl-3-(p-tolyl)-1H- pyrazol-5-yl)piperidine (50) The title compounds were synthesized separately from tert-butyl 4-(1-methyl-5-(p-tolyl)-1H- pyrazol-3-yl)piperidine-1-carboxylate and tert-butyl 4-(1-methyl-3-(p-tolyl)-1H-pyrazol-5- yl)piperidine-1-carboxylate using General Procedure 5. Concentration in vacuo afforded the title compounds. No further purification was conducted. Attorney Docket No.103361-644WO1 Example 44.7-fluoro-2-methoxy-8-(2-(4-(1-methyl-5-(p-tolyl)-1H-pyrazol-3-yl)piperidin- 1-yl)ethyl)-1,5-naphthyridine and 7-fluoro-2-methoxy-8-(2-(4-(1-methyl-3-(p-tolyl)-1H- pyrazol-5-yl)piperidin-1-yl)ethyl)-1,5-naphthyridine The title compounds were synthesized separately from 2-(3-fluoro-6-methoxy-1,5- naphthyridin-4-yl)acetaldehyde and either 4-(1-methyl-5-(p-tolyl)-1H-pyrazol-3-yl)piperidine or 4-(1-methyl-5-(p-tolyl)-1H-pyrazol-3-yl)piperidine using General Procedure 3. Purification by flash chromatography (ethyl acetate in hexanes) and concentration in vacuo afforded the title compounds. The regioisomers were not assigned. Example 45. 6-(4-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)- 1H-1,2,3-triazol-1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one Attorney Docket No.103361-644WO1 The title compound was synthesized from 2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)acetaldehyde and 6-(4-(piperidin-4-yl)-1H-1,2,3-triazol-1-yl)-2H-benzo[b][1,4]oxazin- 3(4H)-one according to General Procedure 3. Purification by flash chromatography (compound eluted in ethyl acetate) and concentration in vacuo afforded the title compound as a white solid (4 mg, 0.008 mmol, 5.9% yield).1HNMR (DMSO-d6, 400 MHz, contaminated with cyclohexane) δ: 10.93 (s, 1H), 8.78 (s, 1H), 8.47 (s, 1H), 8.29 (d, J = 9.0 Hz, 1H), 7.42 (d, J = 2.6 Hz, 1H), 7.33 (dd, J = 2.5, 8.6 Hz, 1H), 7.25 (d, J = 9.0 Hz, 1H), 7.12 (d, J = 8.6 Hz, 1H), 4.65 (s, 2H), 4.06 (s, 3H), 3.38-3.31 (m, partially obscured by water, 2H), 3.11-3.02 (m, 2H), 2.77-2.69 (m, 3H), 2.26-2.16 (m, 2H), 2.00-1.92 (m, 2H), 1.68-1.56 (m, 2H).13CNMR (DMSO- d6, 100 MHz) δ: HRMS (ESI) m / z calc’d for C26H27FN7O3[M+H]+: 504.21539; found: 504.21512. UPLC: rt: 3.04 min, purity: 95.06%. 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl acetate (51) 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethane-1,2-diol (1 eq) was dissolved in THF (0.2 M), and PPTS (1.2 eq) and trimethyl orthoacetate (1.2 eq) were added. Reaction was allowed to stir for 30 minutes, then water (10 eq) was added in one portion. Reaction was allowed to stir an additional 30 minutes, then further diluted with water and extracted 5 x 15 mL ethyl acetate. The combined organic layers were dried over sodium sulfate, decanted, and concentrated by rotary evaporation to afford a crude mixture that was purified via flash column chromatography (compound eluted in 0-40% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (1.6 g, 5.71 mmol, 40% yield).1HNMR (CDCl3, 400 MHz) δ: 8.64 (d, J = 1.9 Hz, 1H), 8.21 (d, J = 9.1 Hz, 1H), 7.12 (d, J = 9.1 Hz, 1H), 6.88 (dd, J = 3.9, 6.3 Hz, 1H), 4.22 (dd, J = 6.1, 11.7 Hz, 1H), 4.15-4.09 (m, 1H, partially obscured by methyl protons), 4.10 (s, 3H), 2.15 (s, 3H). Attorney Docket No.103361-644WO1 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-oxoethyl acetate (52) 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl acetate (1 eq) was dissolved in DCM (0.2 M), and Dess Martin Periodinane (DMP) (1.2 eq) was added. Reaction was allowed to stir overnight. Upon return, the reaction was diluted with water and extracted 5 x 15 mL ethyl acetate. The combined organic layers were dried over sodium sulfate, decanted, and concentrated via rotary evaporation to afford a crude mixture that was purified via flash column chromatography (compound eluted in 0-30% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound as a white solid (870 mg, 3.13 mmol, 54.77% yield).1HNMR (CDCl3, 400 MHz, contaminated with DCM and ethyl acetate) δ: 9.91 (d, J = 1.6 Hz, 1H), 8.75 (s, 1H), 8.24 (d, J = 9.1 Hz, 1H), 7.13 (d, J = 9.1 Hz, 1H), 6.90 (s, 1H), 4.02 (s, 3H), 2.21 (s, 3H). 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-(4-iodopiperidin-1-yl)ethyl acetate (53) Title compound was synthesized using 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2- oxoethyl acetate and 4-iodopiperidine according to General Procedure 3. Purification by flash chromatography (compound eluted in 0-40% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound and an elimination impurity as a yellow oil (650 mg, 1.37 mmol, 43.9% yield). Attorney Docket No.103361-644WO1 2-(4-azidopiperidin-1-yl)-1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl acetate (54) Title compound was synthesized using 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-(4- iodopiperidin-1-yl)ethyl acetate according to General Procedure 18. Purification by flash chromatography (compound eluted in 0-40% ethyl acetate in hexanes) and concentration in vacuo afforded the title compound contaminated with an elimination product as a yellow oil (520 mg, 1.34 mmol, 97.48% yield). Example 46 Example 46. 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2- hydroxyethyl)piperidin-4-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrazino[2,3-b][1,4]oxazin- 3(4H)-one Title compound was synthesized over two steps as follows. To a solution of 2-(4- azidopiperidin-1-yl)-1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl acetate (0.1 g, 1 equiv) in DMF (2 mL) was added copper iodide (4.8 mg, 0.1 equiv) and triethylamine (14.3 microliters, 0.4 equiv) followed by 6-ethynyl-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (49.5 Attorney Docket No.103361-644WO1 mg, 1.1 equiv), whereupon the mixture turned bright yellow. The reaction was stirred overnight then diluted with water, becoming bright yellow and cloudy. The mixture was extracted 5x15 mL ethyl acetate (discarded), and the aqueous layer was extracted 5x15 mL dichloromethane. The combined organic layers contained a precipitate which was collected by filtration. The precipitate was washed with 100 mL 50% DCM / MeOH, and the filtrate was concentrated to afford the crude product as an orange solid (70 mg). This solid was dissolved in methanol (2.5 mL), and sodium methoxide (13.4 mg, 2 equiv) was added. After stirring overnight, the reaction was diluted with 1M aqueous NaOH and stirred an additional 15 minutes. The reaction was diluted with brine and extracted 5x20 mL 50% MeOH in dichloromethane. The combined organic layers were dried and concentrated to an orange solid that was purified by flash chromatography (eluting in 3% methanol in DCM) and dried in vacuo to afford the title compound as an orange solid (3 mg, 0.006 mmol, 4.6% yield). HRMS (ESI) m / z calc’d for C24H25FN9O4[M+H]+: 522.20080; found: 522.20050. UPLC: rt: 2.68 min, purity: 95.56%. The following compounds can also be prepared according to the above methods from the previously prepared synthetic intermediates identified below: 2022, 13, 955-963.

[0005] Attorney Docket No.103361-644WO1 Compound DCompound9 inBioorg. Med. Chem. Lett. 2013, 23, 5437-5441. Attorney Docket No.103361-644WO1 Compound ECompound9 inBioorg. Med. Chem. Lett. 2016, 26, 2464-2469. Table 1. MICs (µg / mL) of NBTIs against Staphylococcus aureus Attorney Docket No.103361-644WO1 Attorney Docket No.103361-644WO1 aMRSA isolate.bIsolate from individual with cystic fibrosis.c29213-derived strain with amino acid substitution in GyrA domain of S. aureus DNA Gyrase. Table 2. MICs (µg / mL) of NBTIs against representative Gram-negative pathogens Attorney Docket No.103361-644WO1 Attorney Docket No.103361-644WO1 aEfflux-deficient strain. The compositions and methods of the appended claims are not limited in scope by the specific compositions and methods described herein, which are intended as illustrations of a few aspects of the claims, and any compositions and methods that are functionally equivalent are intended to fall within the scope of the claims. Various modifications of the compositions and methods, in addition to those shown and described herein, are intended to fall within the scope of the appended claims. Further, while only representative compositions and method steps disclosed herein are specifically described, other combinations of the compositions and method steps are also intended to fall within the scope of the appended claims, even if not Attorney Docket No.103361-644WO1 specifically recited. Thus, a combination of steps, elements, components, or constituents may be explicitly mentioned herein; however, other combinations of steps, elements, components, and constituents are included, even though not explicitly stated.

Claims

Attorney Docket No.103361-644WO1 WHAT IS CLAIMED IS:

1. A compound of Formula I-A or Formula I-B:or a pharmaceutically acceptable salt thereof, wherein: the dashed line represents a bond that is present or absent, and when the bond is present, R1and R2can be cis or trans; A is a fused bicyclic aryl or bicyclic heteroaryl ring optionally substituted with one or more groups independently selected from Z; or A and R1are brought together with the carbon to which they are attached to form a tricyclic ring optionally substituted with one or more groups independently selected from Z; B is a five- to six-membered heteroaryl ring having 1, 2, or 3 ring heteroatoms selected from N, O, and S, wherein B is optionally substituted with one or more groups independently selected from Z; D is an C5-C15aryl or C5-C15heteroaryl ring optionally substituted with one or more groups independently selected from Z; R1and R2are independently selected from H, OH, Cl, F, Br, I, CN, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, oxo, and C1-C6alkyl or C1- C6alkoxyl optionally substituted with one or more groups selected from Z, or R1is a C1-C3 alkyl or C2-C3 alkenyl, optionally substituted with R9, also bound to A;Attorney Docket No.103361-644WO1 each R3is independently selected from C1-C6 alkyl, C1-C6 cycloalkyl, C5-C15 aryl, C4-C15 heteroaryl, C3-C15 heterocycloalkyl, and C1-C15 heteroalkyl, any of which are optionally substituted with one or more groups selected from Z; R9is H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, CO2NH2, CO2NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, or C1-C6 alkyl or C1-C6 alkoxyl optionally substituted with one or more groups selected from Z; Z is independently selected at each occurrence from halo, nitro, cyano, azido, oxo, C1-C6alkyl, C1-C6 haloalkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, 3- to 8-membered monocyclic or bicyclic heterocycle, 6- to 10-membered monocyclic or bicyclic aryl, 5- to 10-membered monocyclic or bicyclic heteroaryl, RxO-, RxS-, (RxRyN)-, RxO-C(O)-, RxS-C(O)-, (RxRyN)- C(O)-, RxO-S(O)2-, (RxRyN)-S(O)2-, RzC(O)-O-, RzC(O)-(RxN)-, RzS(O)2-O-, RzS(O)2-(RxN)- , RzC(O)-, RzS(O)-, and RzS(O)2-; Rxand Ryare independently selected at each occurrence from hydrogen, C1-C6alkyl, C1- C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, (C3-C7cycloalkyl)-(C0-C3 alkyl)-, (4- to 6-membered heterocycle)-(C0-C3 alkyl)-, (5- to 10-membered monocyclic or bicyclic aryl)-(C0-C3 alkyl)-, (5- to 10-membered monocyclic or bicyclic heteroaryl)-(C0-C3alkyl)-; and Rzis independently selected at each occurrence from hydrogen, halo, C1-C6alkyl, C1- C6haloalkyl, C2-C6alkenyl, C2-C6alkynyl, C3-C7cycloalkyl, 4- to 6-membered heterocycle, 5- to 10-membered monocyclic or bicyclic aryl, 5- to 10-membered monocyclic or bicyclic heteroaryl, -ORx, -SRx, and -NRxRy.

2. The compound of claim 1, wherein B is a five-membered heteroaryl ring having 1, 2, or 3 ring heteroatoms selected from N, O, and S, wherein B is optionally substituted with one or more groups independently selected from Z.

3. The compound of claim 1 or claim 2, wherein B is selected from furanyl, pyrrolyl, pyrazolyl, oxazolyl, imidazolyl, isoxazolyl, and triazolyl is optionally substituted with one or more groups independently selected from Z.

4. The compound of any one of claims 1-3, wherein R1and R2are independently selected from from H, F, CN, OH, and NH2.

5. The compound of any one of claims 1-4, wherein R2is NH2.

6. The compound of any one of claims 1-4, wherein R2is H or OH.

7. The compound of any one of claims 1-6, wherein R1is H or OH.Attorney Docket No.103361-644WO1 8. The compound of any one of claims 1-7, wherein A is a fused bicyclic aryl or bicyclic heteroaryl ring having Formula II:wherein each X is independently CH or N; and R4and R5are independently selected from from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6 alkyl or C1-C6alkoxyl optionally substituted with one or more groups independently selected from Z.

9. The compound of claim 8, wherein R4is selected from H, Cl, F, Br, I, OH, and unsubstituted C1-C6 alkyl or C1-C6 alkoxyl.

10. The compound of claim 8 or claim 9, wherein R4is selected from H, Cl, F, OH, and methoxy.

11. The compound of any one of claims 8-10, wherein R4is selected from F and methoxy.

12. The compound of any one of claims 1-7, wherein A and R1are brought together with the carbon to which they are attached to form a group of Formula IX, X, XI, or XIIAttorney Docket No.103361-644WO1XI XII wherein each X is independently CH, N, or CR8; R4and R5are independently selected from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6 alkyl or C1-C6 alkoxyl optionally substituted with one or more groups independently selected from Z; each R8is independently Cl, F, CN, OH, OCH3, CH3, or NH2; and R9is H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, or C1-C6 alkyl or C1-C6 alkoxyl optionally substituted with one or more groups independently selected from Z.

13. The compound of claim 12, wherein R4is H and R5is F.

14. The compound of any one of claims 1-13, wherein D is selected from Formula IV-VIII or XIII:Attorney Docket No.103361-644WO1VIII XIII wherein each X is independently selected from CH or N; each Y is independently selected from O, S, NH, or CH2; and R6and R7are independently selected from H, Cl, F, Br, I, CN, OH, NO2, NH2, CF3, CO2H, OC(O)NH2, OC(O)NHR3, CO2R3, C(O)R3, C(O)NH2, C(O)NHR3, and C1-C6 alkyl or C1-C6 alkoxyl optionally substituted with one or more groups independently selected from Z.

15. The compound of claim 14, wherein R6and R7are independently selected from H, Cl, F, Br, I, CN, OH, and unsubstituted C1-C6 alkyl or C1-C6 alkoxyl.

16. The compound of claim 14, wherein R6and R7are independently selected from H, Cl, F, CN, OH, and methoxy.

17. The compound of claim 14, wherein R6and R7are both H.

18. The compound any one of claims 14-17, wherein each Y is O.

19. The compound of any one of claims 14-17, wherein one Y is S and the other is O.

20. The compound of any one of claims 14-17, wherein one Y is NH and the other is O.

21. The compound of any one of claims 14-17, wherein one Y is NH and the other is S.Attorney Docket No.103361-644WO1 22. The compound of any one of claims 1-21, wherein the dashed line is a bond that is present.

23. The compound of any one of claims 1-21, wherein the dashed line is a bond that absent.

24. The compound of claim 1, wherein the compound is selected from: 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)furan-2-yl)piperidin-1-yl)ethyl)-1,5-naphthyridine (example 1); 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)furan-2-yl)piperidin-1-yl)ethyl)-7-fluoro-2- methoxy-1,5-naphthyridine (example 2); 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)furan-2-yl)-2H- benzo[b][1,4]oxazin-3(4H)-one (example 3); 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-pyrrol-2-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 4); 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrrol-2-yl)piperidin-1-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 5); 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-pyrrol-2-yl)- 2H-benzo[b][1,4]oxazin-3(4H)-one (example 6); 5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-2-(p-tolyl)oxazole (example 7); 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)ethyl)piperidin-4-yl)oxazole (example 8); 3-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-5-(p-tolyl)isoxazole (example 9); 5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-3-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)ethyl)piperidin-4-yl)isoxazole (example 10); 6-(3-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)isoxazol-5-yl)- 2H-benzo[b][1,4]oxazin-3(4H)-one (example 11); 5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-3-(p-tolyl)isoxazole (example 12);Attorney Docket No.103361-644WO1 3-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4- yl)ethyl)piperidin-4-yl)isoxazole (example 13); 6-(5-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)isoxazol-3-yl)- 2H-benzo[b][1,4]oxazin-3(4H)-one (example 14); 7-fluoro-2-methoxy-8-(2-(4-(1-(p-tolyl)-1H-1,2,3-triazol-4-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 15); 8-(2-(4-(1-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-4-yl)piperidin-1-yl)ethyl)- 7-fluoro-2-methoxy-1,5-naphthyridine (example 16); 7-fluoro-2-methoxy-8-(2-(4-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 17); 8-(2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)ethyl)- 7-fluoro-2-methoxy-1,5-naphthyridine (example 18); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 19); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (example 20); 8-(2-(4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)ethyl)-7-fluoro-2- methoxy-1,5-naphthyridine (example 21); 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-imidazol-2-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 22); 7-fluoro-2-methoxy-8-(2-(4-(4-(p-tolyl)-1H-pyrazol-1-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 23); 8-(2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-1-yl)piperidin-1-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 24); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-pyrazol-4- yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 25); 1-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-(4-(4-(p-tolyl)-1H-1,2,3-triazol-1- yl)piperidin-1-yl)ethan-1-ol (example 26);Attorney Docket No.103361-644WO1 2-(4-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)-1-(3- fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol (example 27); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl)piperidin-4-yl)-1H- 1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 28); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl)piperidin-4-yl)-1H- 1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (example 29); 2-(4-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)piperidin-1-yl)-1-(3-fluoro-6-methoxy- 1,5-naphthyridin-4-yl)ethan-1-ol (example 30); 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 4-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (example 31); 7-fluoro-2-methoxy-8-(2-((2r,5r)-5-(4-(p-tolyl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2-yl)ethyl)- 1,5-naphthyridine (example 32); 8-(2-((2r,5r)-5-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2- yl)ethyl)-7-fluoro-2-methoxy-1,5-naphthyridine (example 33); 6-(1-((2r,5r)-2-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)-1,3-dioxan-5-yl)-1H- 1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 34); 8-(2-((2r,5r)-5-(4-(3,4-dichlorophenyl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 35); (S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-((2r,5S)-5-(4-(p-tolyl)-1H-1,2,3-triazol- 1-yl)-1,3-dioxan-2-yl)ethan-1-ol (example 36); (S)-1-((2r,5S)-5-(4-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan- 2-yl)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol (example 37); 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-hydroxyethyl)-1,3- dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 38); 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-hydroxyethyl)-1,3- dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (example 39); (S)-1-((2r,5S)-5-(4-(5,6-dichloropyrazin-2-yl)-1H-1,2,3-triazol-1-yl)-1,3-dioxan-2-yl)-2-(3- fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethan-1-ol (example 40);Attorney Docket No.103361-644WO1 6-(1-((2r,5S)-2-((S)-2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-1-hydroxyethyl)-1,3- dioxan-5-yl)-1H-1,2,3-triazol-4-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (example 41); 7-fluoro-2-methoxy-8-(2-(4-(5-(p-tolyl)-1H-pyrazol-3-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 42); 8-(2-(4-(5-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-1H-pyrazol-3-yl)piperidin-1-yl)ethyl)-7- fluoro-2-methoxy-1,5-naphthyridine (example 43); 7-fluoro-2-methoxy-8-(2-(4-(1-methyl-5-(p-tolyl)-1H-pyrazol-3-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 44, first regioisomer); 7-fluoro-2-methoxy-8-(2-(4-(1-methyl-3-(p-tolyl)-1H-pyrazol-5-yl)piperidin-1-yl)ethyl)-1,5- naphthyridine (example 44, second regioisomer); 6-(4-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)ethyl)piperidin-4-yl)-1H-1,2,3-triazol- 1-yl)-2H-benzo[b][1,4]oxazin-3(4H)-one (example 45); and 6-(1-(1-(2-(3-fluoro-6-methoxy-1,5-naphthyridin-4-yl)-2-hydroxyethyl)piperidin-4-yl)-1H- 1,2,3-triazol-4-yl)-2H-pyrazino[2,3-b][1,4]oxazin-3(4H)-one (example 46); or a pharmaceutically acceptable salt thereof.

25. The compound of any one of claims 1-24, wherein the compound is a type II topoisomerase inhibitor.

26. A pharmaceutical composition comprising a compound of any one of claims 1-25, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or excipient.

27. A method of treating an infection in a subject in need thereof comprising administering a compound of any one of claims 1-25, or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition of claim 26.

28. The method of claim 27, wherein the infection is a Staphylococcus aureus infection.

29. The method of claim 27, wherein the infection is a methicillin-resistant Staphylococcus aureus (MRSA) infection.

30. The method of claim 27, wherein the infection is an Escherichia coli, Acinetobacter baumannii, Pseudomonas aeruginosa, or Salmonella enterica infection.

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