Biaryl compounds and use thereof for modulating a kinase cascade

Abstract

The application relates to biaryl compounds, such as the compound of formula (A): (see formula A) pharmaceutical compositions comprising the compounds, and methods of use the compounds for treating cell proliferation disorders.

Description

BIARYL COMPOUNDS AND USE THEREOF FOR MODULATING A KINASE CASCADE RELATED APPLICATION This application claims priority to, and the benefit of, U.S. Provisional Application No. 62 / 374,201, filed on August 12, 2016. BACKGROUND Signal transduction is any process by which a cell converts one kind of signal or stimulus into another. One class of molecules involved in signal transduction is the kinase family of enzymes. Protein kinases are a large class of enzymes which catalyze the transfer of the <com:Math><semantics>γ<annotation encoding="application / x-tex">\gamma< / annotation>< / semantics>< / com:Math>- phosphate from ATP to the hydroxyl group on the side chain of Ser / Thr or Tyr in proteins and peptides and are intimately involved in the control of various important cell functions, perhaps most notably: signal transduction, differentiation, and proliferation. Phosphorylation of proteins by kinases is an important mechanism in signal transduction for regulation of enzyme activity. The tyrosine kinases are divided into two groups; those that are cytoplasmic proteins and the transmembrane receptor-linked kinases. Because kinases are involved in the regulation of a wide variety of normal cellular signal transduction pathways (e.g., cell growth, differentiation, survival, adhesion, migration, etc.), kinases are thought to play a role in a variety of diseases and disorders. Thus, modulation of kinase signaling cascades may be an important way to treat or prevent such diseases and disorders. One promising potential therapeutic use for protein kinase or protein phosphatase inhibitors is as anti-cancer agents. Small molecule interference with tubulin dynamics has broad and profound effect on a cell. When small molecules bind to tubulin they can interfere with the dynamics of microtubules formed from tubulin, either by stabilizing the formed microtubules so they cannot break down or by preventing new formation of microtubules by polymerization. The effect of small molecules interfering with tubulin dynamics can manifest in the suppression of the cell's ability to proliferate. Interference by small molecules on tubulin dynamics can force the cell to arrest at the G2 / M point in the cell cycle, ceasing mitosis, and triggering apoptosis. This action makes these small molecules efficacious in treating human diseases associated with uncontrolled cell proliferation. Efficacy in treating hyper-proliferative disorders has been proven by compounds such as Paclitaxel (a microtubule stabilizer) and Vinblastin (a tubulin polymerization inhibitor) in human subjects. Tubulin-targeting small molecules can also affect vascularization of tissue. Several tubulin polymerization inhibitors have been demonstrated to affect the abnormal vascularization of tumors. These effects manifest in, e.g., normalization of the vascular network and cutting off blood flow to cancerous tumors, resulting in necrosis. These vascular effects may also be useful for other disease states resulting from abnormal vascularization, such as ocular myopathy. There is a need for small molecule compounds that modulate the kinase signaling cascade as well as tubulin dynamics. The present application addresses such need. SUMMARY Compounds of the application are useful in modulating a component of the kinase signaling cascade or in targeting tubulin. Some compounds may be useful in modulation of more than one component of a kinase signaling cascade. The compounds of the present application are useful as pharmaceutical agents. The compounds of the application may be useful for modulating regulation of a kinase which may be involved in a normal cellular signal transduction pathway (e.g., cell growth, differentiation, survival, adhesion, migration, etc.), or a kinase involved in a disease or disorder. The compounds of the application are useful as tubulin polymerization inhibitors. The compounds of the application are useful in treating diseases and disorders that are modulated by tyrosine kinase inhibition. For example, the compounds of the application are useful in treating diseases and disorders that are modulated by Src kinase. The compounds of the application may also be useful in treating diseases and disorders that are modulated by focal adhesion kinase (FAK). The compounds of the application may also be useful in treating diseases and disorders that are related to tubulin or tubulin polymerization. For example, the compounds of the application may be useful as anti-proliferative agents, for treating mammals, such as for treating humans and animals. The compounds of the application may be used without limitation, for example, as anti-cancer agents. The compounds of the application may be soluble in aqueous solution and in general organic solvents. The present application relates to a compound of formula (A): [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein each of the variables in formula (A) is defined and exemplified herein. In one aspect, a compound of formula (A) is a compound of any one of formula (I), (II), (III), (IVa)-(IVd), (Va)-(Vd), (VIa)-(VId), or (VIIa)-(VIIe): [Image disponible dans le document PDF, Image available in the PDF document] 10 [Image disponible dans le document PDF, Image available in the PDF document] **** [Image disponible dans le document PDF, Image available in the PDF document] (IVc) 1), (Va) (Vc) [VIa) ا و (VIc) [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (VIIa), (VIIb), [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (VIIc), [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein each of the variables is defined and exemplified herein. In one aspect, the application relates to a pharmaceutical composition comprising a compound of the application, or a pharmaceutically acceptable salt, solvate, or prodrug thereof and a pharmaceutically acceptable carrier. In one aspect, the application relates to a method of preventing or treating a disease or disorder comprising administering to a subject in need thereof an effective amount of a compound of the application, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application. In one aspect, the application relates to the use of a compound of the application, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application for preventing or treating a disease or disorder in a subject in need thereof. In one aspect, the application relates to the use of a compound of the application, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application in the manufacture of a medicament for preventing or treating a disease or disorder in a subject in need thereof. In one aspect, the application relates to a compound of the application, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application for use in preventing or treating a disease or disorder in a subject in need thereof. The above description sets forth rather broadly the more important features of the present application in order that the detailed description thereof that follows may be understood, and in order that the present contributions to the art may be better appreciated. Other objects and features of the present application will become apparent from the following detailed description considered in conjunction with the examples. BRIEF DESCRIPTION OF THE DRAWINGS Figure 1A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in TJ905 cells. Figure 1B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in TJ905 cells. Figure 2A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in JEG-3 cells. Figure 2B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in JEG-3 cells. Figure 3A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SW579 cells. Figure 3B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SW579 cells. Figure 4A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in KYSE-150 cells. Figure 4B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in KYSE-150 cells. Figure 5A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in 143B cells. Figure 5B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in 143B cells. Figure 6A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HT-1080 cells. Figure 6B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HT-1080 cells. Figure 7A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in KP4 cells. Figure 7B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in KP4 cells. Figure 8A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HCT-15 cells. Figure 8B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HCT-15 cells. Figure 9A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SK-N-FI cells. Figure 9B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SK-N-FI cells. Figure 10A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HuCCT1 cells. Figure 10B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HuCCT1cells. Figure 11A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in AsPC-1 cells. Figure 11B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in AsPC-1 cells. Figure 12A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in OVCAR-3 cells. Figure 12B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in OVCAR-3 cells. Figure 13A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in MDA-MB-453 cells. Figure 13B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in MDA-MB-453 cells. Figure 14A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in RPMI 8226 cells. Figure 14B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in RPMI 8226 cells. Figure 15A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in NCI-H226 cells. Figure 15B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in NCI-H226 cells. Figure 16A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HCT-116 cells. Figure 16B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HCT-116 cells. Figure 17A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in JHH-5 cells. Figure 17B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in JHH-5 cells. Figure 18A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in A-172 cells. Figure 18B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in A-172 cells. Figure 19A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SK-OV-3 cells. Figure 19B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SK-OV-3 cells. Figure 20A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in MDA-MB-468 cells. Figure 20B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in MDA-MB-468 cells. Figure 21A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in NCI-H1155 cells. Figure 21B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in NCI-H1155 cells. Figure 22A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in MX-1 cells. Figure 22B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in MX-1 cells. Figure 23A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HT-1376 cells. Figure 23B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HT-1376 cells. Figure 24A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HUH-7 cells. Figure 24B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HUH-7 cells. Figure 25A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HeLa cells. Figure 25B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HeLa cells. Figure 26A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in K-562 cells. Figure 26B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in K-562 cells. Figure 27A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HT-29 cells. Figure 27B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HT-29 cells. Figure 28A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in NCI-H1975 cells. Figure 28B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in NCI-H1975 cells. Figure 29A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in FaDu cells. Figure 29B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in FaDu cells. Figure 30A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HL-60 cells. Figure 30B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HL-60 cells. Figure 31A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in MDA-MB-231 cells. Figure 31B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in MDA-MB-231 cells. Figure 32A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in 786-O cells. Figure 32B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in 786-O cells. Figure 33A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in Raji cells. Figure 33B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in Raji cells. Figure 34A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in Molt-4 cells. Figure 34B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in Molt-4 cells. Figure 35A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in KARPAS-299 cells. Figure 35B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in KARPAS-299 cells. Figure 36A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in BT474 cells. Figure 36B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in BT474 cells. Figure 37A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in NCI-H209 cells. Figure 37B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in NCI-H209 cells. Figure 38A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in PC-3 cells. Figure 38B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in PC-3 cells. Figure 39A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in MES-SA / DX5 cells. Figure 39B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in MES-SA / DX5 cells. Figure 40A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SK-MEL-28 cells. Figure 40B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SK-MEL-28 cells. Figure 41A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in AN3 CA cells. Figure 41B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin AN3 CA cells. Figure 42A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HuT 78 cells. Figure 42B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in HuT 78 cells. Figure 43A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in 22Rv1 cells. Figure 43B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in 22Rv1 cells. Figure 44A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in A2058 cells. Figure 44B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in A2058 cells. Figure 45A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SCC-4 cells. Figure 45B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SCC-4 cells. Figure 46A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SNU-5 cells. Figure 46B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in SNU-5 cells. Figure 47A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in EBC-1 cells. Figure 47B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in EBC-1 cells. Figure 48A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in A-673 cells. Figure 48B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in A-673 cells. Figure 49A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in U251 cells. Figure 49B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in U251 cells. Figure 50A is a graph indicating the determination of the IC<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in NCI-N87 cells. Figure 50B is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121 and cisplatin in NCI-N87 cells. Figure 51 is a graph indicating the determination of the GI<com:Sub>50< / com:Sub> for Compound 121, Compound X, and Compound Y in CCD-1106 KERTr keratinocyte cells. Figure 52 compares several pharmacological and physical properties of Compound 121 and Compound Y. Figure 53A is a graph indicating the growth of tumors in a U87-luc human glioblastoma subcutaneous xenograft tumor model mice dosed with vehicle. Figure 53B is a graph indicating the growth of tumors in a U87-luc human glioblastoma subcutaneous xenograft tumor model mice orally dosed with Compound 121. Figure 53C is a graph indicating the effect of treatment on time to terminal sacrifice of U87-luc human glioblastoma subcutaneous xenograft tumor model mice treated with Compound 121 compared to a control. Figure 54A is a graph indicating that Compound 121 extends survival and supports long term tumor control in the GL261 syngeneic murine model of human glioblastoma compared to Compound Y and a control. Figure 54B is a graph indicating that Compound 121-treated mice that achieve long term survival (LTS) reject a sub-cutaneous challenge with GL261 cells. DETAILED DESCRIPTION The details of one or more embodiments of the application are set forth in the accompanying description below. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, the preferred methods and materials are now described. Other features, objects, and advantages of the application will be apparent from the description. In the specification, the singular forms also include the plural unless the context clearly dictates otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. In the case of conflict, the present specification will control. The present application relates to a compound of formula (A): [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein: <com:Math><semantics>Xa<annotation encoding="application / x-tex">X_a< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRa<annotation encoding="application / x-tex">CR^a< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>N<annotation encoding="application / x-tex">N< / annotation>< / semantics>< / com:Math>; X<com:Sub>b< / com:Sub> is CR<com:Sup>b< / com:Sup> or N; X<com:Sub>c< / com:Sub> is CR<com:Sup>c< / com:Sup> or N; X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup> or N; R<com:Sup>a< / com:Sup> is H, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, or C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl; R<com:Sup>b< / com:Sup> is H, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, or C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl; R<com:Sup>c< / com:Sup> is H, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, or C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl; <com:Math><semantics>ℝd<annotation encoding="application / x-tex">\mathbb{R}^d< / annotation>< / semantics>< / com:Math> is H, halogen, <com:Math><semantics>ℂ1<annotation encoding="application / x-tex">\mathbb{C}_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ6<annotation encoding="application / x-tex">\mathbb{C}_6< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>ℂ2<annotation encoding="application / x-tex">\mathbb{C}_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ6<annotation encoding="application / x-tex">\mathbb{C}_6< / annotation>< / semantics>< / com:Math> alkenyl, or <com:Math><semantics>ℂ2<annotation encoding="application / x-tex">\mathbb{C}_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ6<annotation encoding="application / x-tex">\mathbb{C}_6< / annotation>< / semantics>< / com:Math> alkynyl; R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup> are each independently H, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl, or O-(C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl); alternatively, R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup>, together with the carbon atom to which they are attached, form a 3-8 membered saturated, unsaturated, or partially saturated carbocycle, or a saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-7 membered rings and one or more heteroatoms selected from N, O, and S; alternatively, one of R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup>, together with the carbon atom to which R<com:Sup>1< / com:Sup> or R<com:Sup>2< / com:Sup> is attached and (B), form a 7-12 membered saturated, unsaturated, or partially saturated carbocycle, or a 7-12 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S; R<com:Sup>3< / com:Sup> and R<com:Sup>4< / com:Sup> are each independently (a) H, (b) halogen, (c) OH, (d) COOH, (e) CONH<com:Sub>2< / com:Sub>, (f) NHCOR<com:Sup>101< / com:Sup>, (g) NR<com:Sup>101< / com:Sup>COR<com:Sup>102< / com:Sup>, (h) S(O)<com:Math><semantics>6<annotation encoding="application / x-tex">_{6}< / annotation>< / semantics>< / com:Math>R<com:Sup>101< / com:Sup>, (i) C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, (j) C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, (k) C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl, (1) O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (m) O-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (n) O-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (o) COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (p) COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (q) COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (r) CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (s) CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (t) CONH-(C2-C6 alkynyl), (u) CON(C1-C6 alkyl)2, (v) CON(C2-C6 alkenyl)2, (w) <com:Math><semantics>CON(C2−C6 alkynyl)2<annotation encoding="application / x-tex">CON(C_2-C_6 \text{ alkynyl})_2< / annotation>< / semantics>< / com:Math>, (x) <com:Math><semantics>(C1−C6 alkyl)u−NH2<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_u-NH_2< / annotation>< / semantics>< / com:Math>, (y) <com:Math><semantics>(C2−C6 alkenyl)u−NH2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkenyl})_u-NH_2< / annotation>< / semantics>< / com:Math>, (z) <com:Math><semantics>(C2−C6 alkynyl)u−NH2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkynyl})_u-NH_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>NH2<annotation encoding="application / x-tex">NH_{2}< / annotation>< / semantics>< / com:Math>, (aa1) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-<com:Math><semantics>NH<annotation encoding="application / x-tex">NH< / annotation>< / semantics>< / com:Math>(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (aa2) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-<com:Math><semantics>NH<annotation encoding="application / x-tex">NH< / annotation>< / semantics>< / com:Math>(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (aa3) (C<com:Sub>1< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl)<com:Sub>v< / com:Sub>-NH(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl), (bb1) (<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl)<com:Sub>v< / com:Sub>-NH(<com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl), (bb2) (<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl)<com:Sub>v< / com:Sub>- <com:Math><semantics>NH(C2−C6 alkenyl)<annotation encoding="application / x-tex">NH(C_2-C_6 \text{ alkenyl})< / annotation>< / semantics>< / com:Math>, (bb3) (<com:Math><semantics>C2−C6 alkenyl)<annotation encoding="application / x-tex">C_2-C_6 \text{ alkenyl})< / annotation>< / semantics>< / com:Math>v-<com:Math><semantics>NH(C2−C6 alkynyl)<annotation encoding="application / x-tex">NH(C_2-C_6 \text{ alkynyl})< / annotation>< / semantics>< / com:Math>, (cc1) (<com:Math><semantics>C2−C6 alkynyl)<annotation encoding="application / x-tex">C_2-C_6 \text{ alkynyl})< / annotation>< / semantics>< / com:Math>v-<com:Math><semantics>NH(C1−C6 alkynyl)<annotation encoding="application / x-tex">NH(C_1-C_6 \text{ alkynyl})< / annotation>< / semantics>< / com:Math>v-<com:Math><semantics>NH(C1−C6 alkynyl)<annotation encoding="application / x-tex">NH(C_1-C_6 \text{ alkynyl})< / annotation>< / semantics>< / com:Math>v-<com:Math><semantics>NH(C1−C6 alkynyl)<annotation encoding="application / x-tex">NH(C_1-C_6 \text{ alkynyl})< / annotation>< / semantics>< / com:Math>v-<com:Math><semantics>NH(C1−C6 alkynyl)<annotation encoding="application / x-tex">NH(C_1-C_6 \text{ alkynyl})< / annotation>< / semantics>< / com:Math> alkyl), (cc2) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (cc3) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (dd1) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (dd2) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, (dd3) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> <com:Math><semantics>alkyl)w−N(C2−C6alkynyl)2<annotation encoding="application / x-tex">alkyl)_{w}-N(C_2-C_6 alkynyl)_2< / annotation>< / semantics>< / com:Math>, (ee1) <com:Math><semantics>(C2−C6alkenyl)w−N(C1−C6alkyl)2<annotation encoding="application / x-tex">(C_2-C_6 alkenyl)_{w}-N(C_1-C_6 alkyl)_2< / annotation>< / semantics>< / com:Math>, (ee2) <com:Math><semantics>(C2−C6alkenyl)w−N(C2−C6alkyl)2<annotation encoding="application / x-tex">(C_2-C_6 alkenyl)_{w}-N(C_2-C_6 alkyl)_2< / annotation>< / semantics>< / com:Math> <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl)<com:Sub>2< / com:Sub>, (ee3) (<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl)<com:Sub>w< / com:Sub>-<com:Math><semantics>N(C2<annotation encoding="application / x-tex">N(C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>2< / com:Sub>, (ff1) (<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>w< / com:Sub>-<com:Math><semantics>N(C1<annotation encoding="application / x-tex">N(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl)<com:Sub>2< / com:Sub>, (ff2) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, (ff3) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>2< / com:Sub>, (gg) 3-8 membered saturated, unsaturated, or partially saturated carbocycle, or (hh) 3-8 membered saturated, unsaturated, or partially saturated heterocycle, wherein each of (i)-(hh) is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>; [Image disponible dans le document PDF, Image available in the PDF document] represents a saturated, unsaturated, or partially saturated carbocycle comprising one or two 3-8 membered rings, or a saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-8 membered rings and one or more heteroatoms selected from N, O and S, wherein the two 3-8 membered rings or the two 5-8 membered rings can form a fused or bridged ring structure; [Image disponible dans le document PDF, Image available in the PDF document] represents an aromatic, saturated, unsaturated, or partially saturated carbocycle comprising one or two 3-8 membered rings, or an aromatic, saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-8 membered rings and one or more heteroatoms selected from N, O and S, wherein the two 3-8 membered rings or the two 5-8 membered rings can form a fused or bridged ring structure; each R<com:Sup>5< / com:Sup> is independently (a) halogen, (b) OH, (c) CONH<com:Sub>2< / com:Sub>, (d) COOH, (e) CN, (f) N<com:Sub>3< / com:Sub>, (g) <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl, (h) <com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl, (i) <com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl, (j) <com:Math><semantics>O<annotation encoding="application / x-tex">O< / annotation>< / semantics>< / com:Math>-(<com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl), (k) <com:Math><semantics>O<annotation encoding="application / x-tex">O< / annotation>< / semantics>< / com:Math>-(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl), (l) O-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (m) COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (n) COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (o) COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (p) CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (q) CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (r) CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (s) CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)2, (t) CON(C2-C6 alkenyl)2, (u) CON(C2-C6 alkynyl)2, (v1) (C1-C6 alkyl)v-NH(C1-C6 alkyl), <Formule mathématique disponible dans le document PDF, Math available in the PDF document>$(v2) (C_1-C_6 \text{ alkyl})_v-NH(C_2-C_6 \text{ alkenyl}), (v3) (C_1-C_6 \text{ alkyl})_v-NH(C_2-C_6 \text{ alkynyl}), (w1) (C_2-C_6 \text{ alkyl})_v-NH(C_2-C_6 \text{ alkynyl}), (w1) (C_2-C_6 \text{ alkyl})_v-NH(C_2-C_6 \text{ alkynyl}), (w1) (C_2-C_$ alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (w2) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (w3) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>- <Formule mathématique disponible dans le document PDF, Math available in the PDF document>NH(C_2-C_6 \text{ alkynyl}), (x1) (C_2-C_6 \text{ alkynyl})v-NH(C_1-C_6 \text{ alkyl}), (x2) (C_2-C_6 \text{ alkynyl})v-NH(C_2-C_6 \text{ alkynyl})v-NH(C_2-C_6 \text{ alkynyl})v-NH(C_2-C_6 \text{ alkynyl})v-NH(C_2-C_6 \text{ alkynyl})v-NH(C_2-C_6 \text{ al alkenyl), (x3) (C2-C6 alkynyl)v-NH(C2-C6 alkynyl), (y1) (C1-C6 alkyl)w-N(C1-C6 alkyl)2, (y2) <com:Math><semantics>(C1−C6 alkyl)w−N(C2−C6 alkenyl)2<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_w-N(C_2-C_6 \text{ alkenyl})_2< / annotation>< / semantics>< / com:Math>, (y3) <com:Math><semantics>(C1−C6 alkyl)w−N(C2−C6 alkynyl)2<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_w-N(C_2-C_6 \text{ alkynyl})_2< / annotation>< / semantics>< / com:Math>, (z1) <com:Math><semantics>(C2−C6 alkenyl)w−N(C2−C6 alkenyl)w<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkenyl})_w-N(C_2-C_6 \text{ alkenyl})_w< / annotation>< / semantics>< / com:Math> <com:Math><semantics>N(C1−C6 alkyl)2<annotation encoding="application / x-tex">N(C_1-C_6 \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, (z2) (C2-C6 alkenyl)<com:Sub>w< / com:Sub>-<com:Math><semantics>N(C2−C6 alkenyl)2<annotation encoding="application / x-tex">N(C_2-C_6 \text{ alkenyl})_2< / annotation>< / semantics>< / com:Math>, (z3) (C2-C6 alkenyl)<com:Sub>w< / com:Sub>-<com:Math><semantics>N(C2−C6 alkenyl)2<annotation encoding="application / x-tex">N(C_2-C_6 \text{ alkenyl})_2< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>2< / com:Sub>, (aa1) <com:Math><semantics>(C2−C6 alkynyl)w−N(C1−C6 alkyl)2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkynyl})_w-N(C_1-C_6 \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, (aa2) <com:Math><semantics>(C2−C6 alkynyl)w−N(C2−C6 alkenyl)2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkynyl})_w-N(C_2-C_6 \text{ alkenyl})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(aa3)(C2−C6alkynyl)w−N(C2−C6alkynyl)2<annotation encoding="application / x-tex">(aa3) (C_2-C_6 alkynyl)_w-N(C_2-C_6 alkynyl)_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(bb)S−(C1−C6alkyl)<annotation encoding="application / x-tex">(bb) S-(C_1-C_6 alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(cc)S(O)−(C1−C6alkyl)<annotation encoding="application / x-tex">(cc) S(O)-(C_1-C_6 alkyl)< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(dd)<annotation encoding="application / x-tex">(dd)< / annotation>< / semantics>< / com:Math> S(O)<com:Sub>2< / com:Sub>-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (ee) S-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (ff) S(O)-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (gg) S(O)<com:Sub>2< / com:Sub>-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (hh) S-(C2-C6 alkynyl), (ii) S(O)-(C2-C6 alkynyl), (jj) S(O)2-(C2-C6 alkynyl), (kk) an aromatic, saturated, unsaturated, or partially saturated carbocycle comprising one or two 3-8 membered rings, or (ll) an aromatic, saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-7 membered rings and one or more heteroatoms selected from N, O and S, wherein each of (g)-(ll) is optionally substituted with one or more <com:Math><semantics>ℝ8<annotation encoding="application / x-tex">\mathbb{R}^8< / annotation>< / semantics>< / com:Math>; each R<com:Sup>6< / com:Sup> is independently (a) halogen, (b) OH, (c) CONH<com:Sub>2< / com:Sub>, (d) COOH, (e) CN, (f) N<com:Sub>3< / com:Sub>, (g) C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, (h) C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, (i) C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl, (j) O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (k) O-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (l) O-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (m) COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (n) COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (o) COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (p) CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (q) CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (r) CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (s) CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (t) CON(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, (u) CON(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>2< / com:Sub>, (v1) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (v2) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (v3) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (w1) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (w2) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (w3) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>- <Formule mathématique disponible dans le document PDF, Math available in the PDF document>NH(C_2-C_6 \text{ alkynyl}), (x1) (C_2-C_6 \text{ alkynyl})v-NH(C_1-C_6 \text{ alkyl}), (x2) (C_2-C_6 \text{ alkynyl})v-NH(C_2-C_6 \text{ alkynyl})v-NH(C_2-C_6 \text{ alkynyl})v-NH(C_2-C_6 \text{ alkynyl})v-NH(C_2-C_6 \text{ alkynyl})v-NH(C_2-C_6 \text{ al alkenyl), (x3) (C2-C6 alkynyl)v-NH(C2-C6 alkynyl), (y1) (C1-C6 alkyl)w-N(C1-C6 alkyl)2, (y2) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, (y3) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>2< / com:Sub>, (z1) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>w< / com:Sub>- <com:Math><semantics>N(C1−C6 alkyl)2<annotation encoding="application / x-tex">N(C_1-C_6 \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, (z2) (C2-C6 alkenyl)<com:Sub>w< / com:Sub>-<com:Math><semantics>N(C2−C6 alkenyl)2<annotation encoding="application / x-tex">N(C_2-C_6 \text{ alkenyl})_2< / annotation>< / semantics>< / com:Math>, (z3) (C2-C6 alkenyl)<com:Sub>w< / com:Sub>-<com:Math><semantics>N(C2−C6 alkenyl)2<annotation encoding="application / x-tex">N(C_2-C_6 \text{ alkenyl})_2< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>2< / com:Sub>, (aa1) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (aa2) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, (aa3) <com:Math><semantics>(C2−C6 alkynyl)w−N(C2−C6 alkynyl)2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkynyl})_w-N(C_2-C_6 \text{ alkynyl})_2< / annotation>< / semantics>< / com:Math>, (bb) <com:Math><semantics>S−(C1−C6 alkyl)<annotation encoding="application / x-tex">S-(C_1-C_6 \text{ alkyl})< / annotation>< / semantics>< / com:Math>, (cc) <com:Math><semantics>S(O)−(C1−C6 alkyl)<annotation encoding="application / x-tex">S(O)-(C_1-C_6 \text{ alkyl})< / annotation>< / semantics>< / com:Math>, (dd) S(O)<com:Sub>2< / com:Sub>-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (ee) S-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (ff) S(O)-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (gg) S(O)<com:Sub>2< / com:Sub>-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (hh) <com:Math><semantics>S−(C2−C6 alkynyl)<annotation encoding="application / x-tex">S-(C_2-C_6 \text{ alkynyl})< / annotation>< / semantics>< / com:Math>, (ii) <com:Math><semantics>S(O)−(C2−C6 alkynyl)<annotation encoding="application / x-tex">S(O)-(C_2-C_6 \text{ alkynyl})< / annotation>< / semantics>< / com:Math>, (jj) <com:Math><semantics>S(O)2−(C2−C6 alkynyl)<annotation encoding="application / x-tex">S(O)_2-(C_2-C_6 \text{ alkynyl})< / annotation>< / semantics>< / com:Math>, (kk) an aromatic, saturated, unsaturated, or partially saturated carbocycle comprising one or two 3-8 membered rings, or (ll) an aromatic, saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-7 membered rings and one or more heteroatoms selected from N, O and S, wherein each of (g)-(ll) is optionally substituted with one or more <com:Math><semantics>ℝ9<annotation encoding="application / x-tex">\mathbb{R}^9< / annotation>< / semantics>< / com:Math>; each R<com:Sup>7< / com:Sup> is independently halogen, OH, O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, COOH, CN, N<com:Sub>3< / com:Sub>, 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S; each R<com:Sup>8< / com:Sup> is independently halogen, OH, O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> haloalkyl, COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C1-C6 alkyl), CON(C1-C6 alkyl)2, COOH, CN, N3, 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S; each R<com:Sup>9< / com:Sup> is independently halogen, OH, O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, COOH, CN, N<com:Sub>3< / com:Sub>, 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S; R<com:Sup>101< / com:Sup> and R<com:Sup>102< / com:Sup> are each independently H, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, or C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl; R<com:Sup>11< / com:Sup> is H, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, or C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl; R<com:Sup>12< / com:Sup> is H, halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, or C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl; m is 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; t is 0, 1, or 2; u is 0 or 1; v is 0 or 1; and w is 0 or 1, [Image disponible dans le document PDF, Image available in the PDF document] provided that when m is 1, In one aspect, the present application relates to a compound of formula (A), wherein X<com:Sub>a< / com:Sub> is CR<com:Sup>a< / com:Sup>; and X<com:Sub>b< / com:Sub> is CR<com:Sup>b< / com:Sup>. In another aspect, X<com:Sub>a< / com:Sub> is CR<com:Sup>a< / com:Sup>; and X<com:Sub>b< / com:Sub> is N. In another aspect, X<com:Sub>a< / com:Sub> is N; and <com:Math><semantics>Xb<annotation encoding="application / x-tex">X_b< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRb<annotation encoding="application / x-tex">CR^b< / annotation>< / semantics>< / com:Math>. In another aspect, <com:Math><semantics>Xa<annotation encoding="application / x-tex">X_a< / annotation>< / semantics>< / com:Math> is N; and <com:Math><semantics>Xb<annotation encoding="application / x-tex">X_b< / annotation>< / semantics>< / com:Math> is N. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>a< / com:Sup> is H, halogen, or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>a< / com:Sup> is H. In another aspect, Ra is halogen (e.g., F, Cl, Br, or I). In a further aspect, Ra is F. In another aspect, Ra is C1-C6 alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>a< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>a< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>a< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>b< / com:Sup> is H, halogen, or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>b< / com:Sup> is H. In another aspect, R<com:Sup>b< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>b< / com:Sup> is F. In another aspect, R<com:Sup>b< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>b< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>b< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>b< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>a< / com:Sup> is H; and R<com:Sup>b< / com:Sup> is H. In another aspect, one of R<com:Sup>a< / com:Sup> and R<com:Sup>b< / com:Sup> is H, and the other is halogen (e.g., F, Cl, Br, or I) or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In one aspect, the present application relates to a compound of formula (A), wherein Xa is N; X<com:Sub>b< / com:Sub> is CR<com:Sup>b< / com:Sup>; and R<com:Sup>b< / com:Sup> is H. In another aspect, X<com:Sub>b< / com:Sub> is N; X<com:Sub>a< / com:Sub> is CR<com:Sup>a< / com:Sup>; and R<com:Sup>a< / com:Sup> is H. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>11< / com:Sup> is H. In another aspect, R<com:Sup>11< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>11< / com:Sup> is F. In another aspect, R<com:Sup>11< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>11< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>12< / com:Sup> is H. In another aspect, R<com:Sup>12< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>12< / com:Sup> is F. In another aspect, <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>12< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (A), wherein X<com:Sub>a< / com:Sub> is N; <com:Math><semantics>Xb<annotation encoding="application / x-tex">X_b< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRb<annotation encoding="application / x-tex">CR^b< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>Rb<annotation encoding="application / x-tex">R^b< / annotation>< / semantics>< / com:Math> is H; <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math> is methyl; and <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> is H. In another aspect, <com:Math><semantics>Xa<annotation encoding="application / x-tex">X_a< / annotation>< / semantics>< / com:Math> is N; <com:Math><semantics>Xb<annotation encoding="application / x-tex">X_b< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRb<annotation encoding="application / x-tex">CR^b< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>Rb<annotation encoding="application / x-tex">R^b< / annotation>< / semantics>< / com:Math> is H; R<com:Sup>12< / com:Sup> is methyl; and R<com:Sup>11< / com:Sup> is H. In another aspect, X<com:Sub>a< / com:Sub> is N; X<com:Sub>b< / com:Sub> is CR<com:Sup>b< / com:Sup>; R<com:Sup>b< / com:Sup> is H; R<com:Sup>11< / com:Sup> is H; and R<com:Sup>12< / com:Sup> is H. In one aspect, the present application relates to a compound of formula (A), wherein X<com:Sub>b< / com:Sub> is N; Xa is CR<com:Sup>a< / com:Sup>; R<com:Sup>a< / com:Sup> is H; R<com:Sup>11< / com:Sup> is methyl; and R<com:Sup>12< / com:Sup> is H. In another aspect, Xb is N; Xa is CR<com:Sup>a< / com:Sup>; R<com:Sup>a< / com:Sup> is H; R<com:Sup>12< / com:Sup> is methyl; and R<com:Sup>11< / com:Sup> is H. In another aspect, X<com:Sub>b< / com:Sub> is N; X<com:Sub>a< / com:Sub> is CR<com:Sup>a< / com:Sup>; R<com:Sup>a< / com:Sup> is H; R<com:Sup>11< / com:Sup> is H; and R<com:Sup>12< / com:Sup> is H. In one aspect, the present application relates to a compound of formula <com:Math><semantics>(A)<annotation encoding="application / x-tex">(A)< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>Xc<annotation encoding="application / x-tex">X_c< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRc<annotation encoding="application / x-tex">CR^c< / annotation>< / semantics>< / com:Math>; and <com:Math><semantics>Xd<annotation encoding="application / x-tex">X_d< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRd<annotation encoding="application / x-tex">CR^d< / annotation>< / semantics>< / com:Math>. In another aspect, <com:Math><semantics>Xc<annotation encoding="application / x-tex">X_c< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRc<annotation encoding="application / x-tex">CR^c< / annotation>< / semantics>< / com:Math>; and <com:Math><semantics>Xd<annotation encoding="application / x-tex">X_d< / annotation>< / semantics>< / com:Math> is N. In another aspect, <com:Math><semantics>Xc<annotation encoding="application / x-tex">X_c< / annotation>< / semantics>< / com:Math> is N; and <com:Math><semantics>Xd<annotation encoding="application / x-tex">X_d< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRd<annotation encoding="application / x-tex">CR^d< / annotation>< / semantics>< / com:Math>. In another aspect, <com:Math><semantics>Xc<annotation encoding="application / x-tex">X_c< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>N<annotation encoding="application / x-tex">N< / annotation>< / semantics>< / com:Math>; and <com:Math><semantics>Xd<annotation encoding="application / x-tex">X_d< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>N<annotation encoding="application / x-tex">N< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>c< / com:Sup> is H, halogen, or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, the present application relates to a compound of formula (A), wherein <com:Math><semantics>Rc<annotation encoding="application / x-tex">R^c< / annotation>< / semantics>< / com:Math> is H. In another aspect, R<com:Sup>c< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>c< / com:Sup> is F. In another aspect, R° is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>c< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>c< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>c< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>d< / com:Sup> is H, halogen, or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>d< / com:Sup> is H. In another aspect, R<com:Sup>d< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>d< / com:Sup> is F. In another aspect, R<com:Sup>d< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>d< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>d< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>d< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>c< / com:Sup> is H; and R<com:Sup>d< / com:Sup> is H. In another aspect, one of R<com:Sup>c< / com:Sup> and R<com:Sup>d< / com:Sup> is H, and the other is halogen (e.g., F, Cl, Br, or I) or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In one aspect, the present application relates to a compound of formula <com:Math><semantics>(A)<annotation encoding="application / x-tex">(A)< / annotation>< / semantics>< / com:Math>, wherein <com:Math><semantics>Xc<annotation encoding="application / x-tex">X_c< / annotation>< / semantics>< / com:Math> is CR<com:Sup>c< / com:Sup>; X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup>; R<com:Sup>c< / com:Sup> is H; and R<com:Sup>d< / com:Sup> is H. In one aspect, the present application relates to a compound of formula (A), wherein <com:Math><semantics>Xc<annotation encoding="application / x-tex">X_c< / annotation>< / semantics>< / com:Math> is N; X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup>; and R<com:Sup>d< / com:Sup> is H. In another aspect, X<com:Sub>d< / com:Sub> is N; X<com:Sub>c< / com:Sub> is CR<com:Sup>c< / com:Sup>; and R<com:Sup>c< / com:Sup> is H. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is (a) H, (b) halogen, (c) OH, (d) COOH, (e) CONH<com:Sub>2< / com:Sub>, (f) NHCOR<com:Sup>101< / com:Sup>, (g) NR<com:Sup>101< / com:Sup>COR<com:Sup>102< / com:Sup>, (h) S(O)<com:Sub>t< / com:Sub>R<com:Sup>101< / com:Sup>, (i) C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, (l) O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (o) COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (r) CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (u) CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (x) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>u< / com:Sub>-NH<com:Sub>2< / com:Sub>, (aa1) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (dd1) (C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (gg) 3-8 membered saturated, unsaturated, or partially saturated carbocycle, or (hh) 3-8 membered saturated, unsaturated, or partially saturated heterocycle, each of which is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is H. In another aspect, R<com:Sup>3< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>3< / com:Sup> is F. In another aspect, R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>3< / com:Sup> is methyl. In another aspect, R<com:Sup>3< / com:Sup> is OH. In another aspect, R<com:Sup>3< / com:Sup> is O- C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, <com:Math><semantics>ℝ3<annotation encoding="application / x-tex">\mathbb{R}^3< / annotation>< / semantics>< / com:Math> is O-methyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is COOH, CONH<com:Sub>2< / com:Sub>, COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, and wherein C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, and hexyl, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is NHCOR<com:Sup>101< / com:Sup>, NR<com:Sup>101< / com:Sup>COR<com:Sup>102< / com:Sup>, or S(O)<com:Sub>t< / com:Sub>R<com:Sup>101< / com:Sup>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>u< / com:Sub>-NH<com:Sub>2< / com:Sub>, (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), or (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is <com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is <com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is O-(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl), and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is O-(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl), and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), or CON(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is COO-(C2-C6 alkynyl), CONH-(C2-C6 alkynyl), or CON(C2-C6 alkynyl)2, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is <com:Math><semantics>(C2−C6 alkenyl)u−NH2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkenyl})_u-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C1−C6 alkyl)v−NH(C2−C6 alkenyl)<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_v-NH(C_2-C_6 \text{ alkenyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C2−C6 alkenyl)v−NH(C1−C6 alkyl)<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkenyl})_v-NH(C_1-C_6 \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C2−C6 alkenyl)v−NH(C1−C6 alkyl)<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkenyl})_v-NH(C_1-C_6 \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <Formule mathématique disponible dans le document PDF, Math available in the PDF document>(C_2-C_6 \text{ alkenyl})_v-NH(C_1-C_6 \text{ alk C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, or (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>w< / com:Sub>-N(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>2< / com:Sub>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>3< / com:Sup> is <com:Math><semantics>(C2−C6 alkynyl)u−NH2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkynyl})_u-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C1−C6 alkyl)v−NH(C2−C6 alkynyl)<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_v-NH(C_2-C_6 \text{ alkynyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C2−C6 alkynyl)v−NH(C1−C6 alkyl)<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkynyl})_v-NH(C_1-C_6 \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C2−C6 alkynyl)v−NH(C2−C6 alkenyl),(cc3)(C2−C6 alkynyl)v−NH(C2−C6 alkynyl),(C1−C6 alkyl)w−<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkynyl})_v-NH(C_2-C_6 \text{ alkenyl}), (cc3) (C_2-C_6 \text{ alkynyl})_v-NH(C_2-C_6 \text{ alkynyl}), (C_1-C_6 \text{ alkyl})_w-< / annotation>< / semantics>< / com:Math> N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>2< / com:Sub>, (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, or (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>2< / com:Sub>, and is optionally substituted with one or more R<com:Sup>7< / com:Sup>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is (a) H, (b) halogen, (c) OH, (d) COOH, (e) CONH<com:Sub>2< / com:Sub>, (f) NHCOR<com:Sup>101< / com:Sup>, (g) NR<com:Sup>101< / com:Sup>COR<com:Sup>102< / com:Sup>, (h) S(O)<com:Sub>t< / com:Sub>R<com:Sup>101< / com:Sup>, (i) C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, (l) O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (o) COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (r) CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (u) CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (x) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>u< / com:Sub>-NH<com:Sub>2< / com:Sub>, (aa1) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (dd1) (C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (gg) 3-8 membered saturated, unsaturated, or partially saturated carbocycle, or (hh) 3-8 membered saturated, unsaturated, or partially saturated heterocycle, each of which is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is H. In another aspect, R<com:Sup>4< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>4< / com:Sup> is F. In another aspect, R<com:Sup>4< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>4< / com:Sup> is methyl. In another aspect, R<com:Sup>4< / com:Sup> is OH. In another aspect, R<com:Sup>4< / com:Sup> is O- C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>4< / com:Sup> is O-methyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is COOH, CONH<com:Sub>2< / com:Sub>, COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, and wherein C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, and hexyl, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is NHCOR<com:Sup>101< / com:Sup>, NR<com:Sup>101< / com:Sup>COR<com:Sup>102< / com:Sup>, or S(O)<com:Sub>t< / com:Sub>R<com:Sup>101< / com:Sup>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>u< / com:Sub>-NH<com:Sub>2< / com:Sub>, (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is <com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is <com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is O-(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl), and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is O-(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl), and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), or CON(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), or CON(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>2< / com:Sub>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is (C2-C6 alkenyl)<com:Sub>u< / com:Sub>-NH<com:Sub>2< / com:Sub>, (C1-C6 alkyl)<com:Sub>v< / com:Sub>-NH(C2-C6 alkenyl), (C2-C6 alkenyl)<com:Sub>v< / com:Sub>-NH(C1-C6 alkyl), (C2- C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, or (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>2< / com:Sub>, and is optionally substituted with one or more R<com:Sup>7< / com:Sup>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is (C2-C6 alkynyl)u-NH2, (C1-C6 alkyl)v-NH(C2-C6 alkynyl), (C2-C6 alkynyl)v-NH(C1-C6 alkyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (cc3) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>- <com:Math><semantics>N(C2−C6 alkynyl)2<annotation encoding="application / x-tex">N(C_2-C_6 \text{ alkynyl})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C2−C6 alkynyl)w−N(C1−C6 alkyl)2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkynyl})_w-N(C_1-C_6 \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C2−C6 alkynyl)w−N(C2−C6 alkenyl)2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkynyl})_w-N(C_2-C_6 \text{ alkenyl})_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>(C2−C6 alkynyl)w−N(C2−C6 alkynyl)2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkynyl})_w-N(C_2-C_6 \text{ alkynyl})_2< / annotation>< / semantics>< / com:Math>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>4< / com:Sup> is H; and R<com:Sup>3< / com:Sup> is H. In another aspect, R<com:Sup>4< / com:Sup> is H; and R<com:Sup>3< / com:Sup> is halogen, OH, COOH, CONH<com:Sub>2< / com:Sub>, NHCOR<com:Sup>101< / com:Sup>, <com:Math><semantics>NR101COR102<annotation encoding="application / x-tex">NR^{101}COR^{102}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>S(O)1R101<annotation encoding="application / x-tex">S(O)_{1}R^{101}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_{1}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_{6}< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>O<annotation encoding="application / x-tex">O< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(C1<annotation encoding="application / x-tex">(C_{1}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_{6}< / annotation>< / semantics>< / com:Math> alkyl), <com:Math><semantics>COO<annotation encoding="application / x-tex">COO< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(C1<annotation encoding="application / x-tex">(C_{1}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_{6}< / annotation>< / semantics>< / com:Math> alkyl), <com:Math><semantics>CONH<annotation encoding="application / x-tex">CONH< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(C1<annotation encoding="application / x-tex">(C_{1}< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_{6}< / annotation>< / semantics>< / com:Math> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>u< / com:Sub>-NH<com:Sub>2< / com:Sub>, (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)2, or 5-6 membered saturated, unsaturated, or partially saturated carbocycle. In a further aspect, R<com:Sup>4< / com:Sup> is H; and R<com:Sup>3< / com:Sup> is halogen (e.g., F, Cl, Br, or I), C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i- propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl), OH, or O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>4< / com:Sup> is H; and R<com:Sup>3< / com:Sup> is F, methyl, or O-methyl. In one aspect, the present application relates to a compound of formula (A), wherein <com:Math><semantics>Xc<annotation encoding="application / x-tex">X_c< / annotation>< / semantics>< / com:Math> is CR<com:Sup>c< / com:Sup>; X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup>; R<com:Sup>c< / com:Sup> is H; R<com:Sup>d< / com:Sup> is H; R<com:Sup>3< / com:Sup> is H, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl), or O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i- butyl, t-butyl, pentyl, or hexyl); and R<com:Sup>4< / com:Sup> is H. In a further aspect, wherein X<com:Sub>c< / com:Sub> is CR<com:Sup>c< / com:Sup>; X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup>; R<com:Sup>c< / com:Sup> is H; R<com:Sup>d< / com:Sup> is H; R<com:Sup>3< / com:Sup> is H, methyl, or O-methyl; and R<com:Sup>4< / com:Sup> is H. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>101< / com:Sup> is H. In another aspect, <com:Math><semantics>ℝ101<annotation encoding="application / x-tex">\mathbb{R}^{101}< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>ℂ1<annotation encoding="application / x-tex">\mathbb{C}_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ6<annotation encoding="application / x-tex">\mathbb{C}_6< / annotation>< / semantics>< / com:Math> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t- butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>101< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>102< / com:Sup> is H. In another aspect, <com:Math><semantics>R102<annotation encoding="application / x-tex">R^{102}< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t- butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>102< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>7< / com:Sup> is halogen (e.g., F, Cl, Br, or I), OH, or O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl) (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>7< / com:Sup> is F, OH, or O-methyl. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>7< / com:Sup> is COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, or COOH. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>7< / com:Sup> is CN or N<com:Sub>3< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>7< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>1< / com:Sup> is H, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, or O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl). In one aspect, R<com:Sup>1< / com:Sup> is H. In another aspect, R<com:Sup>1< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, <com:Math><semantics>ℝ1<annotation encoding="application / x-tex">\mathbb{R}^1< / annotation>< / semantics>< / com:Math> is methyl. In another aspect, <com:Math><semantics>ℝ1<annotation encoding="application / x-tex">\mathbb{R}^1< / annotation>< / semantics>< / com:Math> is O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>1< / com:Sup> is O-methyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>2< / com:Sup> is H, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, or O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl). In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>2< / com:Sup> is H. In another aspect, R<com:Sup>2< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>2< / com:Sup> is methyl. In another aspect, R<com:Sup>2< / com:Sup> is O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>2< / com:Sup> is O-methyl. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>1< / com:Sup> is H; and R<com:Sup>2< / com:Sup> is H. In another aspect, one of R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup> is H, and the other is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl or O-(C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl). In one aspect, the present application relates to a compound of formula (A), wherein one of <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math>, together with the carbon atom to which <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is attached and <com:Math><semantics>(B)<annotation encoding="application / x-tex">\binom{B}{}< / annotation>< / semantics>< / com:Math>, form a 7-12 membered saturated, unsaturated, or partially saturated carbocycle. In a further aspect, one of R<com:Sup>1< / com:Sup> and <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math>, together with the carbon atom to which <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math> is attached and <com:Math><semantics>(B)<annotation encoding="application / x-tex">\binom{B}{}< / annotation>< / semantics>< / com:Math>, form a dihydroindene. In one aspect, the present application relates to a compound of formula (A), [Image disponible dans le document PDF, Image available in the PDF document] wherein one of R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup>, together with the carbon atom to which R<com:Sup>1< / com:Sup> or R<com:Sup>2< / com:Sup> is attached and form a 7-12 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>1< / com:Sup> and <com:Math><semantics>ℝ2<annotation encoding="application / x-tex">\mathbb{R}^2< / annotation>< / semantics>< / com:Math>, together with the carbon atom to which they are attached, form a 3-8 membered saturated, unsaturated, or partially saturated carbocycle. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup>, together with the carbon atom to which they are attached, form a saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-7 membered rings and one or more heteroatoms selected from N, O, and S In one aspect, the present application relates to a compound of formula (A), wherein [Image disponible dans le document PDF, Image available in the PDF document] represents a saturated, unsaturated, or partially saturated carbocycle comprising one or two 3-8 membered rings, wherein the two 3-8 membered rings can form a fused or bridged ring structure. In one aspect, the present application relates to a compound of formula (A), wherein [Image disponible dans le document PDF, Image available in the PDF document] represents a saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-8 membered rings and one or more heteroatoms selected from N, O and S, wherein the two 5-8 membered rings can form a fused or bridged ring structure. In one aspect, the present application relates to a compound of formula (A), wherein represents a 5-6 membered saturated, unsaturated, or partially saturated carbocycle. In another aspect, (A) represents a saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S. In a further aspect, (A) represents a saturated heterocycle comprising one or more heteroatoms selected from N, O and S, and is optionally substituted. In a further aspect, the heterocycle comprises a two-ring bridged ring system. In a further aspect, (A) represents an optionally substituted heterocycle selected from: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] 5 [Image disponible dans le document PDF, Image available in the PDF document] In a further aspect, Þ In one aspect, the present application relates to a compound of formula (A), wherein m is 1. In another aspect, m is 2. In another aspect, m is 3. In another aspect, m is 4. In another aspect, m is 5. In another aspect, m is 6. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>5< / com:Sup> is (a) halogen, (b) OH, (c) CONH<com:Sub>2< / com:Sub>, (d) COOH, (e) CN, (f) N<com:Sub>3< / com:Sub>, (g) C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, (h) C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, (j) O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (m) COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (p) CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), or (s) CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, each of which is optionally substituted with one or more R<com:Sup>8< / com:Sup>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, at least one R<com:Sup>5< / com:Sup> is F. In another aspect, at least one R<com:Sup>5< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>5< / com:Sup> is methyl. In another aspect, at least one R<com:Sup>5< / com:Sup> is OH, CN, or N<com:Sub>3< / com:Sub>. In another aspect, at least one R<com:Sup>5< / com:Sup> is O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>5< / com:Sup> is O-methyl. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, CONH<com:Sub>2< / com:Sub>, or COOH In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is CN. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is N<com:Sub>3< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is O-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl). In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is O-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl). In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), or CON(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), or CON(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>2< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), or (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>(C2−C6 alkenyl)w−N(C1−C6 alkyl)2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkenyl})_w-N(C_1-C_6 \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C2−C6 alkenyl)w−N(C2−C6 alkenyl)2<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkenyl})_w-N(C_2-C_6 \text{ alkenyl})_2< / annotation>< / semantics>< / com:Math>, or <com:Math><semantics>(C2−C6 alkenyl)w<annotation encoding="application / x-tex">(C_2-C_6 \text{ alkenyl})_w< / annotation>< / semantics>< / com:Math> <com:Math><semantics>alkenyl)w−N(C2−C6alkynyl)2<annotation encoding="application / x-tex">alkenyl)_{w}-N(C_2-C_6 alkynyl)_2< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (cc<com:Sub>3< / com:Sub>) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>(C2−C6<annotation encoding="application / x-tex">(C_2-C_6< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>w< / com:Sub>-N<com:Math><semantics>(C1−C6<annotation encoding="application / x-tex">(C_1-C_6< / annotation>< / semantics>< / com:Math> alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>(C2−C6<annotation encoding="application / x-tex">(C_2-C_6< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>w< / com:Sub>-N<com:Math><semantics>(C2−C6<annotation encoding="application / x-tex">(C_2-C_6< / annotation>< / semantics>< / com:Math> alkenyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>(C2−C6<annotation encoding="application / x-tex">(C_2-C_6< / annotation>< / semantics>< / com:Math> <com:Math><semantics>alkynyl)w−N(C2−C6alkynyl)2<annotation encoding="application / x-tex">alkynyl)_{w}-N(C_2-C_6 alkynyl)_2< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is S(O)-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), S(O)<com:Sub>2< / com:Sub>-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), S-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), S(O)-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), or <com:Math><semantics>S(O)2<annotation encoding="application / x-tex">S(O)_2< / annotation>< / semantics>< / com:Math>-(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl). In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>5< / com:Sup> is an aromatic, saturated, unsaturated, or partially saturated carbocycle comprising one or two 3-8 membered rings, or an aromatic, saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-7 membered rings and one or more heteroatoms selected from N, O and S. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>5< / com:Sup> is in the S-configuration. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>8< / com:Sup> is halogen (e.g., F, Cl, Br, or I), OH, O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl) (e.g., methyl, ethyl, propyl, i- propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl), or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> haloalkyl (e.g., CHF<com:Sub>2< / com:Sub>, CH<com:Sub>2< / com:Sub>F, CF<com:Sub>3< / com:Sub>, CH<com:Sub>2< / com:Sub>CHF<com:Sub>2< / com:Sub>, CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>F, or CH<com:Sub>2< / com:Sub>CF<com:Sub>3< / com:Sub>). In a further aspect, at least one R<com:Sup>8< / com:Sup> is F, OH, O-methyl, or <com:Math><semantics>𝑪𝑭3<annotation encoding="application / x-tex">\mathbf{CF}_3< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>8< / com:Sup> is COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, or COOH. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>8< / com:Sup> is CN or N<com:Sub>3< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>8< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S. In one aspect, the present application relates to a compound of formula (A), wherein [Image disponible dans le document PDF, Image available in the PDF document] represents a saturated, unsaturated, or partially saturated carbocycle comprising one or two 3-8 membered rings, wherein the two 3-8 membered rings can form a fused or bridged ring structure. In one aspect, the present application relates to a compound of formula (A), wherein represents a saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-8 membered rings and one or more heteroatoms selected from N, O and S, wherein the two 5-8 membered rings can form a fused or bridged ring structure. In one aspect, the present application relates to a compound of formula (A), wherein В represents a 5-6 membered aromatic, saturated, unsaturated, or partially saturated carbocycle. In a further aspect, represents a 6 membered aromatic carbocycle (e.g., phenyl). In a further aspect, (B) represents phenyl. In one aspect, the present application relates to a compound of formula (A), wherein represents an aromatic, saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S. In a further aspect, (B) represents an aromatic heterocycle comprising one or more heteroatoms selected from N, O and S (e.g., pyridine, pyrazine, or pyrimidine). In a further aspect, (B) represents pyridine. In one aspect, the present application relates to a compound of formula (A), wherein n is 0. In another aspect, n is 1, 2, 3, 4, 5, or 6. In a further aspect, n is 1. In one aspect, the present application relates to a compound of formula (A), wherein R<com:Sup>6< / com:Sup> is (a) halogen, (b) OH, (c) CONH<com:Sub>2< / com:Sub>, (d) COOH, (e) CN, (f) N<com:Sub>3< / com:Sub>, (g) C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, (h) C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, (j) O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (m) COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (p) CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), or (s) CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, each of which is optionally substituted with one or more R<com:Sup>9< / com:Sup>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>6< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, at least one R<com:Sup>6< / com:Sup> is F. In a further aspect, R<com:Sup>6< / com:Sup> is 2-fluoro or 4-fluoro. In a further aspect, R<com:Sup>6< / com:Sup> is 2-fluoro. In a further aspect, R<com:Sup>6< / com:Sup> is 4- fluoro. In another aspect, at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>6< / com:Sup> is methyl. In another aspect, at least one R<com:Sup>6< / com:Sup> is OH. In another aspect, at least one R<com:Sup>6< / com:Sup> is O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>6< / com:Sup> is O-methyl. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>6< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl. In one aspect, the present application relates to a compound of formula (A), wherein at least one <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>ℂ2<annotation encoding="application / x-tex">\mathbb{C}_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ6<annotation encoding="application / x-tex">\mathbb{C}_6< / annotation>< / semantics>< / com:Math> alkynyl. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>6< / com:Sup> is COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, CONH<com:Sub>2< / com:Sub>, or COOH. In one aspect, the present application relates to a compound of formula (A), wherein at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is CN. In one aspect, the present application relates to a compound of formula (A), wherein at least one <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>ℕ3<annotation encoding="application / x-tex">\mathbb{N}_3< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (A), wherein at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is O-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl). In one aspect, the present application relates to a compound of formula (A), wherein at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is O-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl). In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>6< / com:Sup> is COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), or CON(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>6< / com:Sup> is COO-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), CONH-(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), or CON(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>2< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>6< / com:Sup> is (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), or (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>6< / com:Sup> is (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)<com:Sub>2< / com:Sub>, or (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl)w-N(C2-C6 alkynyl)2. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>6< / com:Sup> is (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl), (cc3) (C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl), (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>(C2−C6<annotation encoding="application / x-tex">(C_2-C_6< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>w< / com:Sub>-<com:Math><semantics>N(C1−C6<annotation encoding="application / x-tex">N(C_1-C_6< / annotation>< / semantics>< / com:Math> alkyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>(C2−C6<annotation encoding="application / x-tex">(C_2-C_6< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>w< / com:Sub>-<com:Math><semantics>N(C2−C6<annotation encoding="application / x-tex">N(C_2-C_6< / annotation>< / semantics>< / com:Math> alkenyl)<com:Sub>2< / com:Sub>, <com:Math><semantics>(C2−C6<annotation encoding="application / x-tex">(C_2-C_6< / annotation>< / semantics>< / com:Math> alkynyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl)<com:Sub>2< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>S(O)<annotation encoding="application / x-tex">S(O)< / annotation>< / semantics>< / com:Math>-(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl), <com:Math><semantics>S(O)2<annotation encoding="application / x-tex">S(O)_2< / annotation>< / semantics>< / com:Math>-(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkenyl), <com:Math><semantics>S<annotation encoding="application / x-tex">S< / annotation>< / semantics>< / com:Math>-(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl), <com:Math><semantics>S(O)<annotation encoding="application / x-tex">S(O)< / annotation>< / semantics>< / com:Math>-(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl), or <com:Math><semantics>S(O)2<annotation encoding="application / x-tex">S(O)_2< / annotation>< / semantics>< / com:Math>-(<com:Math><semantics>C2<annotation encoding="application / x-tex">C_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkynyl). In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>6< / com:Sup> is an aromatic, saturated, unsaturated, or partially saturated carbocycle comprising one or two 3-8 membered rings, or an aromatic, saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-7 membered rings and one or more heteroatoms selected from N, O and S. In one aspect, the present application relates to a compound of formula (A), wherein at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is bonded to the 2- or 4-position of <com:Math><semantics>(B)<annotation encoding="application / x-tex">\binom{B}{}< / annotation>< / semantics>< / com:Math>. In a further aspect, at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is 2-F, 2-methyl, 2-OH, 2-O-methyl, 2-CN, or 2-N<com:Sub>3< / com:Sub>. In another aspect, at least one R<com:Sup>6< / com:Sup> is 4-F, 4-methyl, 4-OH, 4-O-methyl, 4-CN, or 4-N<com:Sub>3< / com:Sub>. In a further aspect, (B) is phenyl or pyridine; and at least [Image disponible dans le document PDF, Image available in the PDF document] one R<com:Sup>6< / com:Sup> is 2-F, 2-methyl, 2-OH, 2-O-methyl, 2-CN, or 2-N<com:Sub>3< / com:Sub>. In another aspect, is phenyl or pyridine; and at least one R<com:Sup>6< / com:Sup> is 4-F, 4-methyl, 4-OH, 4-O-methyl, 4-CN, or 4-N<com:Sub>3< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>9< / com:Sup> is halogen (e.g., F, Cl, Br, or I), OH, or O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl) (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>9< / com:Sup> is F, OH, or O-methyl. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>9< / com:Sup> is COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, or COOH. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>9< / com:Sup> is CN or N<com:Sub>3< / com:Sub>. In one aspect, the present application relates to a compound of formula (A), wherein at least one R<com:Sup>9< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S. The present application relates to a compound of formula (I): [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein: Xa is CR<com:Sup>a< / com:Sup> or N; X<com:Sub>b< / com:Sub> is CR<com:Sup>b< / com:Sup> or N; X<com:Sub>c< / com:Sub> is CR<com:Sup>c< / com:Sup> or N; X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup> or N; R<com:Sup>a< / com:Sup> is H, halogen, or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl; R<com:Sup>b< / com:Sup> is H, halogen, or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl; R<com:Sup>c< / com:Sup> is H, halogen, or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl; R<com:Sup>d< / com:Sup> is H, halogen, or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl; R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup> are each independently H, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, or O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl); alternatively, one of R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup>, together with the carbon atom to which R<com:Sup>1< / com:Sup> or R<com:Sup>2< / com:Sup> is attached and (B), form a 7-12 membered saturated, unsaturated, or partially saturated carbocycle, or a 7-12 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S; R<com:Sup>3< / com:Sup> and R<com:Sup>4< / com:Sup> are each independently (a) H, (b) halogen, (c) OH, (d) COOH, (e) CONH<com:Sub>2< / com:Sub>, (f) NHCOR<com:Sup>101< / com:Sup>, (g) NR<com:Sup>101< / com:Sup>COR<com:Sup>102< / com:Sup>, (h) S(O)<com:Sub>6< / com:Sub>R<com:Sup>101< / com:Sup>, (i) C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, (j) O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (k) COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (1) CONH-(C1-C6 alkyl), (m) CON(C1-C6 alkyl)2, (n) (C1-C6 alkyl)u-NH2, (o) (C1-C6 alkyl)<com:Sub>v< / com:Sub>-NH(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), (p) (C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>w< / com:Sub>-N(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, or (q) 5-6 membered saturated, unsaturated, or partially saturated carbocycle, wherein each of (i)-(q) is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>; [Image disponible dans le document PDF, Image available in the PDF document] represents a 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or a 5-6 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S; [Image disponible dans le document PDF, Image available in the PDF document] represents a 5-6 membered aromatic, saturated, unsaturated, or partially saturated carbocycle, or a 5-6 membered aromatic, saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S; each R<com:Sup>5< / com:Sup> is independently (a) halogen, (b) OH, (c) C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, (d) C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, (e) O- <com:Math><semantics>(C1−C6 alkyl),(f) COO-(C1−C6 alkyl),(g) CONH-(C1−C6 alkyl),(h) CON(C1−C6 alkyl)2,(i)<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl}), (f) \text{ COO-}(C_1-C_6 \text{ alkyl}), (g) \text{ CONH-}(C_1-C_6 \text{ alkyl}), (h) \text{ CON}(C_1-C_6 \text{ alkyl})_2, (i)< / annotation>< / semantics>< / com:Math> COOH, (j) CN, or (k) N<com:Sub>3< / com:Sub>, wherein each of (c)-(h) is optionally substituted with one or more R<com:Sup>8< / com:Sup>; each R<com:Sup>6< / com:Sup> is independently (a) halogen, (b) OH, (c) C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, (d) C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, (e) O- <com:Math><semantics>(C1−C6 alkyl),(f) COO-(C1−C6 alkyl),(g) CONH-(C1−C6 alkyl),(h) CON(C1−C6 alkyl)2,(i)<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl}), (f) \text{ COO-}(C_1-C_6 \text{ alkyl}), (g) \text{ CONH-}(C_1-C_6 \text{ alkyl}), (h) \text{ CON}(C_1-C_6 \text{ alkyl})_2, (i)< / annotation>< / semantics>< / com:Math> COOH, (j) CN, or (k) N<com:Sub>3< / com:Sub>, wherein each of (c)-(h) is optionally substituted with one or more R<com:Sup>9< / com:Sup>; each R<com:Sup>7< / com:Sup> is independently halogen, OH, O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, COOH, CN, N<com:Sub>3< / com:Sub>, 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S; each R<com:Sup>8< / com:Sup> is independently halogen, OH, O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> haloalkyl, COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, COOH, CN, N<com:Sub>3< / com:Sub>, 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S; each R<com:Sup>9< / com:Sup> is independently halogen, OH, O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, COOH, CN, N<com:Sub>3< / com:Sub>, 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S; <com:Math><semantics>R101<annotation encoding="application / x-tex">R^{101}< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>R102<annotation encoding="application / x-tex">R^{102}< / annotation>< / semantics>< / com:Math> are each independently H or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl; <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math> is H, halogen, or <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl; <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> is H, halogen, or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl; m is 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; t is 0, 1, or 2; u is 0 or 1; v is 0 or 1; and w is 0 or 1, [Image disponible dans le document PDF, Image available in the PDF document] provided that when m is 1, In one aspect, the present application relates to a compound of formula (I), wherein <com:Math><semantics>Xa<annotation encoding="application / x-tex">X_a< / annotation>< / semantics>< / com:Math> is CR<com:Sup>a< / com:Sup>; and X<com:Sub>b< / com:Sub> is CR<com:Sup>b< / com:Sup>. In another aspect, X<com:Sub>a< / com:Sub> is CR<com:Sup>a< / com:Sup>; and X<com:Sub>b< / com:Sub> is N. In another aspect, X<com:Sub>a< / com:Sub> is N; and X<com:Sub>b< / com:Sub> is CR<com:Sup>b< / com:Sup>. In another aspect, X<com:Sub>a< / com:Sub> is N; and X<com:Sub>b< / com:Sub> is N. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>a< / com:Sup> is H. In another aspect, Ra is halogen (e.g., F, Cl, Br, or I). In a further aspect, Ra is F. In another aspect, Ra is C1-C6 alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>a< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>b< / com:Sup> is H. In another aspect, R<com:Sup>b< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>b< / com:Sup> is F. In another aspect, R<com:Sup>b< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>b< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>a< / com:Sup> is H; and R<com:Sup>b< / com:Sup> is H. In another aspect, one of R<com:Sup>a< / com:Sup> and R<com:Sup>b< / com:Sup> is H, and the other is halogen (e.g., F, Cl, Br, or I) or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In one aspect, the present application relates to a compound of formula (I), wherein Xa is N; X<com:Sub>b< / com:Sub> is CR<com:Sup>b< / com:Sup>; and R<com:Sup>b< / com:Sup> is H. In another aspect, X<com:Sub>b< / com:Sub> is N; X<com:Sub>a< / com:Sub> is CR<com:Sup>a< / com:Sup>; and R<com:Sup>a< / com:Sup> is H. In one aspect, the present application relates to a compound of formula (I), wherein <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math> is H. In another aspect, R<com:Sup>11< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>11< / com:Sup> is F. In another aspect, R<com:Sup>11< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>11< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (I), wherein <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> is H. In another aspect, R<com:Sup>12< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>12< / com:Sup> is F. In another aspect, R<com:Sup>12< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> is methyl. In one aspect, the present application relates to a compound of formula (I), wherein X<com:Sub>a< / com:Sub> is N; <com:Math><semantics>Xb<annotation encoding="application / x-tex">X_b< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRb<annotation encoding="application / x-tex">CR^b< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>Rb<annotation encoding="application / x-tex">R^b< / annotation>< / semantics>< / com:Math> is H; <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math> is methyl; and <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> is H. In another aspect, <com:Math><semantics>Xa<annotation encoding="application / x-tex">X_a< / annotation>< / semantics>< / com:Math> is N; <com:Math><semantics>Xb<annotation encoding="application / x-tex">X_b< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>CRb<annotation encoding="application / x-tex">CR^b< / annotation>< / semantics>< / com:Math>; <com:Math><semantics>Rb<annotation encoding="application / x-tex">R^b< / annotation>< / semantics>< / com:Math> is H; R<com:Sup>12< / com:Sup> is methyl; and R<com:Sup>11< / com:Sup> is H. In another aspect, X<com:Sub>a< / com:Sub> is N; X<com:Sub>b< / com:Sub> is CR<com:Sup>b< / com:Sup>; R<com:Sup>b< / com:Sup> is H; R<com:Sup>11< / com:Sup> is H; and R<com:Sup>12< / com:Sup> is H. In one aspect, the present application relates to a compound of formula (I), wherein X<com:Sub>b< / com:Sub> is N; Xa is CR<com:Sup>a< / com:Sup>; R<com:Sup>a< / com:Sup> is H; R<com:Sup>11< / com:Sup> is methyl; and R<com:Sup>12< / com:Sup> is H. In another aspect, X<com:Sub>b< / com:Sub> is N; X<com:Sub>a< / com:Sub> is CR<com:Sup>a< / com:Sup>; R<com:Sup>a< / com:Sup> is H; R<com:Sup>12< / com:Sup> is methyl; and R<com:Sup>11< / com:Sup> is H. In another aspect, X<com:Sub>b< / com:Sub> is N; X<com:Sub>a< / com:Sub> is CR<com:Sup>a< / com:Sup>; R<com:Sup>a< / com:Sup> is H; R<com:Sup>11< / com:Sup> is H; and R<com:Sup>12< / com:Sup> is H. In one aspect, the present application relates to a compound of formula (I), wherein <com:Math><semantics>Xc<annotation encoding="application / x-tex">X_c< / annotation>< / semantics>< / com:Math> is CR<com:Sup>c< / com:Sup>; and X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup>. In another aspect, X<com:Sub>c< / com:Sub> is CR<com:Sup>c< / com:Sup>; and X<com:Sub>d< / com:Sub> is N. In another aspect, X<com:Sub>c< / com:Sub> is N; and X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup>. In another aspect, X<com:Sub>c< / com:Sub> is N; and X<com:Sub>d< / com:Sub> is N. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>c< / com:Sup> is H. In another aspect, R<com:Sup>c< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>c< / com:Sup> is F. In another aspect, R<com:Sup>c< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>c< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>d< / com:Sup> is H. In another aspect, R<com:Sup>d< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>d< / com:Sup> is F. In another aspect, R<com:Sup>d< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>d< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>c< / com:Sup> is H; and R<com:Sup>d< / com:Sup> is H. In another aspect, one of R<com:Sup>c< / com:Sup> and R<com:Sup>d< / com:Sup> is H, and the other is halogen (e.g., F, Cl, Br, or I) or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In one aspect, the present application relates to a compound of formula (I), wherein <com:Math><semantics>Xc<annotation encoding="application / x-tex">X_c< / annotation>< / semantics>< / com:Math> is CR°; X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup>; R° is H; and R<com:Sup>d< / com:Sup> is H. In one aspect, the present application relates to a compound of formula (I), wherein <com:Math><semantics>Xc<annotation encoding="application / x-tex">X_c< / annotation>< / semantics>< / com:Math> is N; X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup>; and R<com:Sup>d< / com:Sup> is H. In another aspect, X<com:Sub>d< / com:Sub> is N; X<com:Sub>c< / com:Sub> is CR<com:Sup>c< / com:Sup>; and R<com:Sup>c< / com:Sup> is H. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>3< / com:Sup> is H. In another aspect, R<com:Sup>3< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>3< / com:Sup> is F. In another aspect, R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>3< / com:Sup> is methyl. In another aspect, R<com:Sup>3< / com:Sup> is OH. In another aspect, R<com:Sup>3< / com:Sup> is O- C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>3< / com:Sup> is O-methyl. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>3< / com:Sup> is COOH, CONH<com:Sub>2< / com:Sub>, COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, and wherein C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, and hexyl, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>3< / com:Sup> is NHCOR<com:Sup>101< / com:Sup>, NR<com:Sup>101< / com:Sup>COR<com:Sup>102< / com:Sup>, or S(O)<com:Sub>t< / com:Sub>R<com:Sup>101< / com:Sup>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>3< / com:Sup> is <com:Math><semantics>(C1−C6 alkyl)u−NH2<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_u-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C1−C6 alkyl)v−NH(C1−C6 alkyl)<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_v-NH(C_1-C_6 \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C1−C6 alkyl)w−N(C1−C6 alkyl)2<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_w-N(C_1-C_6 \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>3< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>4< / com:Sup> is H. In another aspect, R<com:Sup>4< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, R<com:Sup>4< / com:Sup> is F. In another aspect, R<com:Sup>4< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>4< / com:Sup> is methyl. In another aspect, R<com:Sup>4< / com:Sup> is OH. In another aspect, R<com:Sup>4< / com:Sup> is O- C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>4< / com:Sup> is O-methyl. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>4< / com:Sup> is COOH, CONH<com:Sub>2< / com:Sub>, COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, and wherein C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl is selected from methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, and hexyl, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>4< / com:Sup> is NHCOR<com:Sup>101< / com:Sup>, NR<com:Sup>101< / com:Sup>COR<com:Sup>102< / com:Sup>, or S(O)<com:Sub>t< / com:Sub>R<com:Sup>101< / com:Sup>, and is optionally substituted with one or more R<com:Sup>7< / com:Sup>. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>4< / com:Sup> is <com:Math><semantics>(C1−C6 alkyl)u−NH2<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_u-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C1−C6 alkyl)v−NH(C1−C6 alkyl)<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_v-NH(C_1-C_6 \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C1−C6 alkyl)w−N(C1−C6 alkyl)2<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_w-N(C_1-C_6 \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>4< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, and is optionally substituted with one or more <com:Math><semantics>ℝ7<annotation encoding="application / x-tex">\mathbb{R}^7< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>4< / com:Sup> is H; and R<com:Sup>3< / com:Sup> is H. In another aspect, R<com:Sup>4< / com:Sup> is H; and R<com:Sup>3< / com:Sup> is halogen, OH, COOH, CONH<com:Sub>2< / com:Sub>, NHCOR<com:Sup>101< / com:Sup>, <com:Math><semantics>NR101COR102<annotation encoding="application / x-tex">NR^{101}COR^{102}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>S(O)0R101<annotation encoding="application / x-tex">S(O)_0R^{101}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>O<annotation encoding="application / x-tex">O< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(C1<annotation encoding="application / x-tex">(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl), <com:Math><semantics>COO<annotation encoding="application / x-tex">COO< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(C1<annotation encoding="application / x-tex">(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl), <com:Math><semantics>CONH<annotation encoding="application / x-tex">CONH< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>(C1<annotation encoding="application / x-tex">(C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl), <com:Math><semantics>CON(C1−C6 alkyl)2<annotation encoding="application / x-tex">CON(C_1-C_6 \text{ alkyl})_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C1−C6 alkyl)u−NH2<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_u-NH_2< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C1−C6 alkyl)v−NH(C1−C6 alkyl)<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_v-NH(C_1-C_6 \text{ alkyl})< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>(C1−C6 alkyl)w−N(C1−C6 alkyl)<annotation encoding="application / x-tex">(C_1-C_6 \text{ alkyl})_w-N(C_1-C_6 \text{ alkyl})< / annotation>< / semantics>< / com:Math> alkyl)<com:Sub>2< / com:Sub>, or 5-6 membered saturated, unsaturated, or partially saturated carbocycle. In a further aspect, R<com:Sup>4< / com:Sup> is H; and R<com:Sup>3< / com:Sup> is halogen (e.g., F, Cl, Br, or I), C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i- propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl), OH, or O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>4< / com:Sup> is H; and R<com:Sup>3< / com:Sup> is F, methyl, or O-methyl. In one aspect, the present application relates to a compound of formula (I), wherein <com:Math><semantics>Xc<annotation encoding="application / x-tex">X_c< / annotation>< / semantics>< / com:Math> is CR<com:Sup>c< / com:Sup>; X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup>; R<com:Sup>c< / com:Sup> is H; R<com:Sup>d< / com:Sup> is H; R<com:Sup>3< / com:Sup> is H, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl), or O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i- butyl, t-butyl, pentyl, or hexyl); and R<com:Sup>4< / com:Sup> is H. In a further aspect, wherein X<com:Sub>c< / com:Sub> is CR<com:Sup>c< / com:Sup>; X<com:Sub>d< / com:Sub> is CR<com:Sup>d< / com:Sup>; R<com:Sup>c< / com:Sup> is H; R<com:Sup>d< / com:Sup> is H; R<com:Sup>3< / com:Sup> is H, methyl, or O-methyl; and R<com:Sup>4< / com:Sup> is H. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>101< / com:Sup> is H. In another aspect, <com:Math><semantics>ℝ101<annotation encoding="application / x-tex">\mathbb{R}^{101}< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>ℂ1<annotation encoding="application / x-tex">\mathbb{C}_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ6<annotation encoding="application / x-tex">\mathbb{C}_6< / annotation>< / semantics>< / com:Math> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t- butyl, pentyl, or hexyl). In a further aspect, <com:Math><semantics>R101<annotation encoding="application / x-tex">R^{101}< / annotation>< / semantics>< / com:Math> is methyl. In one aspect, the present application relates to a compound of formula (I), wherein <com:Math><semantics>R102<annotation encoding="application / x-tex">R^{102}< / annotation>< / semantics>< / com:Math> is H. In another aspect, <com:Math><semantics>R102<annotation encoding="application / x-tex">R^{102}< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t- butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>102< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>7< / com:Sup> is halogen (e.g., F, Cl, Br, or I), OH, or O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl) (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>7< / com:Sup> is F, OH, or O-methyl. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>7< / com:Sup> is COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, or COOH. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>7< / com:Sup> is CN or N<com:Sub>3< / com:Sub>. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>7< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>1< / com:Sup> is H. In another aspect, R<com:Sup>1< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t- butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>1< / com:Sup> is methyl. In another aspect, R<com:Sup>1< / com:Sup> is O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, <com:Math><semantics>ℝ1<annotation encoding="application / x-tex">\mathbb{R}^1< / annotation>< / semantics>< / com:Math> is O-methyl. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>2< / com:Sup> is H. In another aspect, <com:Math><semantics>ℝ2<annotation encoding="application / x-tex">\mathbb{R}^2< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>ℂ1<annotation encoding="application / x-tex">\mathbb{C}_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ6<annotation encoding="application / x-tex">\mathbb{C}_6< / annotation>< / semantics>< / com:Math> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t- butyl, pentyl, or hexyl). In a further aspect, R<com:Sup>2< / com:Sup> is methyl. In another aspect, R<com:Sup>2< / com:Sup> is O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, <com:Math><semantics>ℝ2<annotation encoding="application / x-tex">\mathbb{R}^2< / annotation>< / semantics>< / com:Math> is O-methyl. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>1< / com:Sup> is H; and R<com:Sup>2< / com:Sup> is H. In another aspect, one of R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup> is H, and the other is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl or O-(C<com:Sub>1< / com:Sub>- C<com:Sub>6< / com:Sub> alkyl). In one aspect, the present application relates to a compound of formula (I), wherein one [Image disponible dans le document PDF, Image available in the PDF document] of <com:Math><semantics>ℝ1<annotation encoding="application / x-tex">\mathbb{R}^1< / annotation>< / semantics>< / com:Math> and <com:Math><semantics>ℝ2<annotation encoding="application / x-tex">\mathbb{R}^2< / annotation>< / semantics>< / com:Math>, together with the carbon atom to which <com:Math><semantics>ℝ1<annotation encoding="application / x-tex">\mathbb{R}^1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>ℝ2<annotation encoding="application / x-tex">\mathbb{R}^2< / annotation>< / semantics>< / com:Math> is attached and , form a 7-12 membered saturated, unsaturated, or partially saturated carbocycle. In a further aspect, one of R<com:Sup>1< / com:Sup> [Image disponible dans le document PDF, Image available in the PDF document] and R<com:Sup>2< / com:Sup>, together with the carbon atom to which R<com:Sup>1< / com:Sup> or R<com:Sup>2< / com:Sup> is attached and , form a dihydroindene, i.e., indane or benzocyclopentane. In one aspect, the present application relates to a compound of formula (I), wherein one of R<com:Sup>1< / com:Sup> and R<com:Sup>2< / com:Sup>, together with the carbon atom to which [Image disponible dans le document PDF, Image available in the PDF document] <com:Math><semantics>ℝ1<annotation encoding="application / x-tex">\mathbb{R}^1< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>ℝ2<annotation encoding="application / x-tex">\mathbb{R}^2< / annotation>< / semantics>< / com:Math> is attached and , form a 7-12 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S. [Image disponible dans le document PDF, Image available in the PDF document] In one aspect, the present application relates to a compound of formula (I), wherein represents a 5-6 membered saturated, unsaturated, or partially saturated carbocycle. In another [Image disponible dans le document PDF, Image available in the PDF document] aspect, represents a saturated, unsaturated, or partially saturated heterocycle containing one [Image disponible dans le document PDF, Image available in the PDF document] or more heteroatoms selected from N, O and S. In a further aspect, represents a saturated heterocycle containing one or more heteroatoms selected from N, O and S, and is optionally substituted. In a further aspect, the heterocycle comprises a two-ring bridged ring system. In a [Image disponible dans le document PDF, Image available in the PDF document] further aspect, represents an optionally substituted heterocycle selected from: [Image disponible dans le document PDF, Image available in the PDF document] , [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] In a further aspect, ٠ In one aspect, the present application relates to a compound of formula (I), wherein m is 1. In another aspect, m is 2. In another aspect, m is 3. In another aspect, m is 4. In another aspect, m is 5. In another aspect, m is 6. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>5< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, at least one R<com:Sup>5< / com:Sup> is F. In another aspect, at least one R<com:Sup>5< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>5< / com:Sup> is methyl. In another aspect, at least one R<com:Sup>5< / com:Sup> is OH, CN, or N<com:Sub>3< / com:Sub>. In another aspect, at least one R<com:Sup>5< / com:Sup> is O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>5< / com:Sup> is O-methyl. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>5< / com:Sup> is C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl. In one aspect, the present application relates to a compound of formula (I), wherein R<com:Sup>5< / com:Sup> is in the S-configuration. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>5< / com:Sup> is COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, or COOH. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>8< / com:Sup> is halogen (e.g., F, Cl, Br, or I), OH, O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl) (e.g., methyl, ethyl, propyl, i- propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl), or C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> haloalkyl (e.g., CHF<com:Sub>2< / com:Sub>, CH<com:Sub>2< / com:Sub>F, CF<com:Sub>3< / com:Sub>, CH<com:Sub>2< / com:Sub>CHF<com:Sub>2< / com:Sub>, CH<com:Sub>2< / com:Sub>CH<com:Sub>2< / com:Sub>F, or CH<com:Sub>2< / com:Sub>CF<com:Sub>3< / com:Sub>). In a further aspect, at least one R<com:Sup>8< / com:Sup> is F, OH, O-methyl, or CF<com:Sub>3< / com:Sub>. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>8< / com:Sup> is COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, or COOH. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>8< / com:Sup> is CN or N<com:Sub>3< / com:Sub>. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>8< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S. [Image disponible dans le document PDF, Image available in the PDF document] In one aspect, the present application relates to a compound of formula (I), wherein represents a 5-6 membered aromatic, saturated, unsaturated, or partially saturated carbocycle. In [Image disponible dans le document PDF, Image available in the PDF document] a further aspect, represents a 6 membered aromatic carbocycle (e.g., phenyl). In a further [Image disponible dans le document PDF, Image available in the PDF document] aspect, represents phenyl. [Image disponible dans le document PDF, Image available in the PDF document] In one aspect, the present application relates to a compound of formula (I), wherein represents an aromatic, saturated, unsaturated, or partially saturated heterocycle containing one [Image disponible dans le document PDF, Image available in the PDF document] or more heteroatoms selected from N, O and S. In a further aspect, represents an aromatic heterocycle containing one or more heteroatoms selected from N, O and S (e.g., pyridine, [Image disponible dans le document PDF, Image available in the PDF document] pyrazine, or pyrimidine). In a further aspect, represents pyridine. In one aspect, the present application relates to a compound of formula (I), wherein n is 0. In another aspect, n is 1, 2, 3, 4, 5, or 6. In a further aspect, n is 1. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>6< / com:Sup> is halogen (e.g., F, Cl, Br, or I). In a further aspect, at least one R<com:Sup>6< / com:Sup> is F. In a further aspect, R<com:Sup>6< / com:Sup> is 2-fluoro or 4-fluoro. In a further aspect, R<com:Sup>6< / com:Sup> is 2-fluoro. In a further aspect, R<com:Sup>6< / com:Sup> is 4- fluoro. In another aspect, at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>6< / com:Sup> is methyl. In another aspect, at least one R<com:Sup>6< / com:Sup> is OH. In another aspect, at least one R<com:Sup>6< / com:Sup> is O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>6< / com:Sup> is O-methyl. In one aspect, the present application relates to a compound of formula (I), wherein at least one <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>ℂ2<annotation encoding="application / x-tex">\mathbb{C}_2< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ6<annotation encoding="application / x-tex">\mathbb{C}_6< / annotation>< / semantics>< / com:Math> alkenyl. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>6< / com:Sup> is COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, or COOH. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>6< / com:Sup> is CN. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>6< / com:Sup> is N<com:Sub>3< / com:Sub>. In one aspect, the present application relates to a compound of formula (I), wherein at [Image disponible dans le document PDF, Image available in the PDF document] least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is bonded to the 2- or 4-position of . In a further aspect, at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is 2-F, 2-methyl, 2-OH, 2-O-methyl, 2-CN, or 2-N<com:Sub>3< / com:Sub>. In another aspect, at least one R<com:Sup>6< / com:Sup> is 4-F, 4-methyl, 4-OH, 4-O-methyl, 4-CN, or 4-N<com:Sub>3< / com:Sub>. In a further aspect, (B) is phenyl or pyridine; and at least one R<com:Sup>6< / com:Sup> is 2-F, 2-methyl, 2-OH, 2-O-methyl, 2-CN, or 2-N<com:Sub>3< / com:Sub>. In another aspect, (B) is phenyl or pyridine; and at least one R<com:Sup>6< / com:Sup> is 4-F, 4-methyl, 4-OH, 4-O-methyl, 4-CN, or 4-N<com:Sub>3< / com:Sub>. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>9< / com:Sup> is halogen (e.g., F, Cl, Br, or I), OH, or O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl) (e.g., methyl, ethyl, propyl, i-propyl, butyl, i-butyl, t-butyl, pentyl, or hexyl). In a further aspect, at least one R<com:Sup>9< / com:Sup> is F, OH, or O-methyl. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>9< / com:Sup> is COO-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CONH-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), CON(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl)<com:Sub>2< / com:Sub>, or COOH. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>9< / com:Sup> is CN or N<com:Sub>3< / com:Sub>. In one aspect, the present application relates to a compound of formula (I), wherein at least one R<com:Sup>9< / com:Sup> is 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S. In one aspect, the present application relates to a compound of formula (I), wherein at least one of R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>11< / com:Sup>, or R<com:Sup>12< / com:Sup> is methyl. In a further aspect, one of R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>11< / com:Sup>, or R<com:Sup>12< / com:Sup> is methyl. In one aspect, the present application relates to a compound of formula (I), wherein at R<com:Sup>3< / com:Sup> is methyl and <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> are H. In one aspect, the present application relates to a compound of formula (I), wherein at R<com:Sup>4< / com:Sup> is methyl and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> are H. In one aspect, the present application relates to a compound of formula (I), wherein at R<com:Sup>11< / com:Sup> is methyl and <com:Math><semantics>ℝ3<annotation encoding="application / x-tex">\mathbb{R}^3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>ℝ4<annotation encoding="application / x-tex">\mathbb{R}^4< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>ℝ12<annotation encoding="application / x-tex">\mathbb{R}^{12}< / annotation>< / semantics>< / com:Math> are H. In one aspect, the present application relates to a compound of formula (I), wherein at <com:Math><semantics>ℝ12<annotation encoding="application / x-tex">\mathbb{R}^{12}< / annotation>< / semantics>< / com:Math> is methyl and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math> are H. In one aspect, the present application relates to a compound of formula (I), wherein at least one of R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>11< / com:Sup>, or R<com:Sup>12< / com:Sup> is O-methyl. In a further aspect, one of R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>11< / com:Sup>, or R<com:Sup>12< / com:Sup> is O- methyl. In one aspect, the present application relates to a compound of formula (I), wherein at R<com:Sup>3< / com:Sup> is O-methyl and <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> are H. In one aspect, the present application relates to a compound of formula (I), wherein at R<com:Sup>4< / com:Sup> is O-methyl and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> are H. In one aspect, the present application relates to a compound of formula (I), wherein at R<com:Sup>11< / com:Sup> is O-methyl and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>R12<annotation encoding="application / x-tex">R^{12}< / annotation>< / semantics>< / com:Math> are H. In one aspect, the present application relates to a compound of formula (I), wherein at R<com:Sup>12< / com:Sup> is O-methyl and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R4<annotation encoding="application / x-tex">R^4< / annotation>< / semantics>< / com:Math>, and <com:Math><semantics>R11<annotation encoding="application / x-tex">R^{11}< / annotation>< / semantics>< / com:Math> are H. In one aspect, the present application relates to a compound of formula (II): [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein each of the variables is as defined in formula (I). In a further aspect, (A), (B), R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup>, R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>5< / com:Sup>, R<com:Sup>6< / com:Sup>, R<com:Sup>11< / com:Sup>, R<com:Sup>12< / com:Sup>, m, and n are selected from the moieties described herein. In one aspect, the present application relates to a compound of formula (III): [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein each of <com:Math><semantics>⌣(A)<annotation encoding="application / x-tex">\stackrel{(A)}{\smile}< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R1<annotation encoding="application / x-tex">R^1< / annotation>< / semantics>< / com:Math>, <com:Math><semantics>R2<annotation encoding="application / x-tex">R^2< / annotation>< / semantics>< / com:Math>, R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>5< / com:Sup>, R<com:Sup>6< / com:Sup>, R<com:Sup>11< / com:Sup>, R<com:Sup>12< / com:Sup>, and m is as defined in formula (I), and n1 is 0, 1, 2, 3, 4, or 5. In a further aspect, (A), R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup>, R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>5< / com:Sup>, R<com:Sup>6< / com:Sup>, R<com:Sup>11< / com:Sup>, R<com:Sup>12< / com:Sup>, and m are selected from the moieties described herein. In a further aspect, n1 is 0. In another aspect, n1 is 1. In one aspect, the present application relates to a compound of a formula selected from: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (IVa), (IVb), [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (IVc), (IVd), or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein each of R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup>, R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>5< / com:Sup>, R<com:Sup>6< / com:Sup>, R<com:Sup>11< / com:Sup>, R<com:Sup>12< / com:Sup>, and m is as defined in formula (I); R<com:Sup>51< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, O-(C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl), COO-(C1-C6 alkyl), CONH-(C1-C6 alkyl), CON(C1-C6 alkyl)2, or CN, each of which is optionally substituted with one or more R<com:Sup>8< / com:Sup>; and m1 is 0, 1, 2, 3, or 4. In a further aspect, R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup>, R<com:Sup>3< / com:Sup>, R<com:Sup>4< / com:Sup>, R<com:Sup>5< / com:Sup>, R<com:Sup>6< / com:Sup>, R<com:Sup>11< / com:Sup>, R<com:Sup>12< / com:Sup>, and m are selected from the moieties described herein. In a further aspect, m1 is 0. In another aspect, m1 is 1. In a further aspect, each of the substituents defined for R<com:Sup>51< / com:Sup> can be selected from the moieties described herein for the corresponding substituent defined for R<com:Sup>5< / com:Sup>. In one aspect, the present application relates to a compound of a formula selected from: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (Va), (Vb), [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (Vc), (Vd), or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein each of the variables is as defined in formula (I). In a further aspect, R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup>, R<com:Sup>5< / com:Sup>, and R<com:Sup>6< / com:Sup> are selected from the moieties described herein. In one aspect, the present application relates to a compound of a formula selected from: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (VIa), (VIb), [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] (VIc), (VId), or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein each of the variables is as defined in formula (I). In a further aspect, R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup>, R<com:Sup>5< / com:Sup>, and R<com:Sup>6< / com:Sup> are selected from the moieties described herein. In one aspect, the present application relates to a compound of formula (VIIa), (VIIb), (VIIc), (VIId), or (VIIe): [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] ١, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, wherein each of R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup>, R<com:Sup>3< / com:Sup>, R<com:Sup>5< / com:Sup>, and R<com:Sup>6< / com:Sup> is as defined in formula (I); n2 is 0, 1, 2, or 3; n3 is 0, 1, or 2; A<com:Sup>1< / com:Sup>, A<com:Sup>2< / com:Sup>, and A<com:Sup>3< / com:Sup> are each independently CR<com:Sup>61< / com:Sup> or N, wherein only one of A<com:Sup>1< / com:Sup>, A<com:Sup>2< / com:Sup>, and A<com:Sup>3< / com:Sup> is N; and each R<com:Sup>61< / com:Sup> is independently H or R<com:Sup>6< / com:Sup>. In a further aspect, R<com:Sup>1< / com:Sup>, R<com:Sup>2< / com:Sup>, R<com:Sup>3< / com:Sup>, R<com:Sup>5< / com:Sup>, and R<com:Sup>6< / com:Sup> are selected from the moieties described herein. In one aspect, R<com:Sup>3< / com:Sup> is H, methyl, or O-methyl. In a further aspect, R<com:Sup>3< / com:Sup> is methyl or O- methyl. In a further aspect, <com:Math><semantics>ℝ3<annotation encoding="application / x-tex">\mathbb{R}^3< / annotation>< / semantics>< / com:Math> is methyl. In one aspect, R<com:Sup>5< / com:Sup> is methyl. In one aspect, <com:Math><semantics>ℝ5<annotation encoding="application / x-tex">\mathbb{R}^5< / annotation>< / semantics>< / com:Math> is in the S-configuration. In one aspect, n2 is 0. In another aspect, n2 is 1. In one aspect, n3 is 0. In another aspect, n3 is 1. In one aspect, R<com:Sup>6< / com:Sup> is halogen, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, O-C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, or CN. In one aspect, R<com:Sup>6< / com:Sup> is F, methyl, O-methyl, or CN. In a further aspect, R<com:Sup>6< / com:Sup> is F, O-methyl, or CN. In a further aspect, R<com:Sup>6< / com:Sup> is at the 2- or 4-position. In a further aspect, at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is F. In a further aspect, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is 2- fluoro or 4-fluoro. In a further aspect, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is 2-fluoro. In a further aspect, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is 4-fluoro. In one aspect, <com:Math><semantics>A1<annotation encoding="application / x-tex">A^1< / annotation>< / semantics>< / com:Math> is N. In another aspect, <com:Math><semantics>A2<annotation encoding="application / x-tex">A^2< / annotation>< / semantics>< / com:Math> is N. In another aspect, <com:Math><semantics>A3<annotation encoding="application / x-tex">A^3< / annotation>< / semantics>< / com:Math> is N. In one aspect, <com:Math><semantics>R61<annotation encoding="application / x-tex">R^{61}< / annotation>< / semantics>< / com:Math> is H. In another aspect, <com:Math><semantics>R61<annotation encoding="application / x-tex">R^{61}< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>R6<annotation encoding="application / x-tex">R^{6}< / annotation>< / semantics>< / com:Math>. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl and R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl and R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, methyl and R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, methyl and R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl and <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is methyl. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl and R<com:Sup>3< / com:Sup> is methyl. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, methyl and R<com:Sup>3< / com:Sup> is methyl. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math> alkyl and at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is, methyl and at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is, methyl and at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein <com:Math><semantics>ℝ3<annotation encoding="application / x-tex">\mathbb{R}^3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>ℂ1<annotation encoding="application / x-tex">\mathbb{C}_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ6<annotation encoding="application / x-tex">\mathbb{C}_6< / annotation>< / semantics>< / com:Math> alkyl and at least one <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein <com:Math><semantics>ℝ3<annotation encoding="application / x-tex">\mathbb{R}^3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>ℂ1<annotation encoding="application / x-tex">\mathbb{C}_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>ℂ3<annotation encoding="application / x-tex">\mathbb{C}_3< / annotation>< / semantics>< / com:Math> alkyl and at least one <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein R<com:Sup>3< / com:Sup> is methyl and at least one <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein <com:Math><semantics>ℝ3<annotation encoding="application / x-tex">\mathbb{R}^3< / annotation>< / semantics>< / com:Math> is methyl and at least one <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, methyl, R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is, methyl, <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math> alkyl, and at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, R<com:Sup>6< / com:Sup> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, R<com:Sup>3< / com:Sup> is methyl, and at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is, <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math> alkyl, <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is methyl, and at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, R<com:Sup>6< / com:Sup> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, methyl, R<com:Sup>3< / com:Sup> is methyl, and at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, halogen. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, methyl, R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, methyl, R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, R<com:Sup>3< / com:Sup> is methyl, and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, R<com:Sup>5< / com:Sup> is, C<com:Sub>1< / com:Sub>-C<com:Sub>3< / com:Sub> alkyl, R<com:Sup>3< / com:Sup> is methyl, and at least one R<com:Sup>6< / com:Sup> is, or as where applicable, R<com:Sup>6< / com:Sup> is, F. In one aspect, the present application relates to a compound of any of the formulae herein, wherein at least one R<com:Sup>5< / com:Sup> is, or as where applicable, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is, methyl, <com:Math><semantics>R3<annotation encoding="application / x-tex">R^3< / annotation>< / semantics>< / com:Math> is methyl, and at least one <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, or as where applicable, <com:Math><semantics>R6<annotation encoding="application / x-tex">R^6< / annotation>< / semantics>< / com:Math> is, F. Representative compounds of the application are listed in Table 1. Table 1 [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] 130 In one aspect, a compound of the application displays high brain permeability. Brain permeability can be measured by various methods known in the art. For example, brain permeability can be measured by calculating the ratio between the concentration of a compound of the application in the brain and the concentration of the compound in the plasma (i.e., B:P ratio). In one aspect, a compound of the application has a B:P ratio of at least 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, or 2.0 at 1 hour after administration of the compound to a subject. In one aspect, a compound of the application has a B:P ratio of at least 1.5, 1.6, 1.7, 1.8, 1.9, or 2.0 at 1 hour after administration of the compound to a subject. In one aspect, a compound of the application has a B:P ratio of at least 1.4, 1.5, 1.6, 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, or 2.3 at 2 hours after administration of the compound to a subject. In one aspect, a compound of the application has a B:P ratio of at least 1.9, 2.0, 2.1, 2.2, or 2.3 at 2 hours after administration of the compound to a subject. In one aspect, a compound of the application has a B:P ratio of at least 1.7, 1.8, 1.9, 2.0, 2.1, 2.2, 2.3, 2.4, or 2.5 at 4 hours after administration of the compound to a subject. In one aspect, a compound of the application has a B:P ratio of at least 2.2, 2.3, 2.4, or 2.5 at 4 hours after administration of the compound to a subject. In one aspect, the compound that displays high brain permeability is a compound of formula (VIIa), (VIIb), (VIIc), (VIId), or (VIIe) wherein R<com:Sup>6< / com:Sup> is F. In a further aspect, the compound that displays high brain permeability is a compound of formula (VIIa), (VIIb), (VIIc), (VIId), or (VIIe), wherein R<com:Sup>6< / com:Sup> is 2-fluoro or 4-fluoro. In a further aspect, the compound that displays high brain permeability is a compound of formula (VIIa), (VIIb), (VIIc), (VIId), or (VIIe), wherein R<com:Sup>6< / com:Sup> is 2-fluoro. In a further aspect, the compound that displays high brain permeability is a compound of formula (VIIa), (VIIb), (VIIc), (VIId), or (VIIe), wherein <com:Math><semantics>ℝ6<annotation encoding="application / x-tex">\mathbb{R}^6< / annotation>< / semantics>< / com:Math> is 4-fluoro. In one aspect, a compound of the application displays a low melting point (M.P.). In one aspect, a low M.P. is below 150 °C, 145 °C, 140 °C, 135 °C, 130 °C, 125 °C, 120 °C, 115 °C, 110 °C, 105 °C, 100 °C, 95 °C, 90 °C, or 85 °C. In a further aspect, a low M.P. is below 115 °C, 110 °C, 105 °C, 100 °C, 95 °C, 90 °C, or 85 °C. In one aspect, the compound that has a low M.P. is any compound of the application, wherein R<com:Sup>3< / com:Sup> is not H. In a further aspect, R<com:Sup>3< / com:Sup> is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In a further aspect, R<com:Sup>3< / com:Sup> is methyl. In one aspect, a compound of the application displays improved aqueous solubility [Image disponible dans le document PDF, Image available in the PDF document] compared to , i.e., Compound Y, a compound known to be useful in treating diseases and disorders that are modulated by tyrosine kinase inhibition, at a pH of 4.4. In one aspect, a compound of the application is about 10 to about 100 times more soluble in water at a pH of 4.4 compared to Compound Y. In a further aspect, the compound is about 15 to about 75 times more soluble in water at a pH of 4.4 compared to Compound Y. In a further aspect, the compound is about 20 to about 50 times more soluble in water at a pH of 4.4 compared to Compound Y. In a further aspect, the compound is about 20 times more soluble in water at a pH of 4.4 compared to Compound Y. In a further aspect, the compound is about 30 times more soluble in water at a pH of 4.4 compared to Compound Y. In a further aspect, the compound is about 40 times more soluble in water at a pH of 4.4 compared to Compound Y. In a further aspect, the compound is about 50 times more soluble in water at a pH of 4.4 compared to Compound Y. In one aspect, a compound of the application has a solubility of about 30 µM to about 100 μM in water at a pH of 4.4. In a further aspect, the compound has a solubility of about 40 μM to about 90 μM in water at a pH of 4.4. In a further aspect, the compound has a solubility of about 40 µM to about 80 µM in water at a pH of 4.4. In a further aspect, the compound has a solubility of about 40 <com:Math><semantics>μ<annotation encoding="application / x-tex">\mu< / annotation>< / semantics>< / com:Math>M to about 70 <com:Math><semantics>μ<annotation encoding="application / x-tex">\mu< / annotation>< / semantics>< / com:Math>M in water at a pH of 4.4. In a further aspect, the compound has a solubility of about 40 µM in water at a pH of 4.4. In a further aspect, the compound has a solubility of about 50 µM in water at a pH of 4.4. In a further aspect, the compound has a solubility of about 60 µM in water at a pH of 4.4. In a further aspect, the compound has a solubility of about 70 µM in water at a pH of 4.4. In a further aspect, the compound has a solubility of about 80 µM in water at a pH of 4.4. In a further aspect, the compound has a solubility of about 90 µM in water at a pH of 4.4. In one aspect, a compound of the application displays improved aqueous solubility compared to Compound Y at a pH of 7.4. In one aspect, a compound of the application is about 5 to about 60 times more soluble in water at a pH of 7.4 compared to Compound Y. In a further aspect, the compound is about 10 to about 50 times more soluble in water at a pH of 7.4 compared to Compound Y. In a further aspect, the compound is about 15 to about 40 times more soluble in water at a pH of 7.4 compared to Compound Y. In a further aspect, the compound is about 10 to about 20 times more soluble in water at a pH of 7.4 compared to Compound Y. In a further aspect, the compound is about 20 to about 30 times more soluble in water at a pH of 7.4 compared to Compound Y. In a further aspect, the compound is about 30 to about 40 times more soluble in water at a pH of 7.4 compared to Compound Y. In a further aspect, the compound is about 40 to about 50 times more soluble in water at a pH of 7.4 compared to Compound Y. In one aspect, a compound of the application has a solubility of about 10 µM to about 40 μM in water at a pH of 7.4. In a further aspect, the compound has a solubility of about 15 μM to about 30 µM in water at a pH of 7.4. In a further aspect, the compound has a solubility of about 15 <com:Math><semantics>μ<annotation encoding="application / x-tex">\mu< / annotation>< / semantics>< / com:Math>M in water at a pH of 7.4. In a further aspect, the compound has a solubility of about 20 <com:Math><semantics>μ<annotation encoding="application / x-tex">\mu< / annotation>< / semantics>< / com:Math>M in water at a pH of 7.4. In a further aspect, the compound has a solubility of about 25 <com:Math><semantics>μ<annotation encoding="application / x-tex">\mu< / annotation>< / semantics>< / com:Math>M. In a further aspect, the compound has a solubility of about 30 µM in water at a pH of 7.4. In one aspect, the application relates to a pharmaceutical composition comprising a compound of the application, or a pharmaceutically acceptable salt, solvate, or prodrug thereof, and a pharmaceutically acceptable carrier. In one aspect, the application relates to a method of preventing or treating a disease or disorder comprising administering to a subject in need thereof an effective amount of a compound of the application, e.g., a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, VIa, VIb, VIc, VId, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application. In one aspect, the application relates to a method of preventing or treating a disease or disorder comprising administering to a subject in need thereof an effective amount of a compound of the application, e.g., a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, VIa, VIb, VIc, VId, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application, wherein R<com:Sup>5< / com:Sup> is in the S-configuration. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, CONH<com:Sub>2< / com:Sub>, COOH, CN, N<com:Sub>3< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, and C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is halogen. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is OH. In one aspect, R<com:Sup>5< / com:Sup> is in the S- configuration and is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is methyl. In one aspect, the application relates to the use of a compound of the application, <com:Math><semantics>e.g.<annotation encoding="application / x-tex">e.g.< / annotation>< / semantics>< / com:Math>, a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, VIa, VIb, VIc, VId, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application, for preventing or treating a disease or disorder in a subject in need thereof. In one aspect, the application relates to the use of a compound of the application, <com:Math><semantics>e.g.<annotation encoding="application / x-tex">e.g.< / annotation>< / semantics>< / com:Math>, a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, VIa, VIb, VIc, VId, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application, for preventing or treating a disease or disorder in a subject in need thereof, wherein R<com:Sup>5< / com:Sup> is in the S-configuration. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, CONH2, COOH, CN, N<com:Sub>3< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, and C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S- configuration and is selected from the group consisting of halogen, OH, and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is halogen. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is OH. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is methyl. In one aspect, the application relates to the use of a compound of the application, e.g., a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, VIa, VIb, VIc, VId, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application, in the manufacture of a medicament for preventing or treating a disease or disorder in a subject in need thereof. In one aspect, the application relates to the use of a compound of the application, <com:Math><semantics>e.g.<annotation encoding="application / x-tex">e.g.< / annotation>< / semantics>< / com:Math>, a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, VIa, VIb, VIc, VId, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application, in the manufacture of a medicament for preventing or treating a disease or disorder in a subject in need thereof, wherein R<com:Sup>5< / com:Sup> is in the S-configuration. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, CONH<com:Sub>2< / com:Sub>, COOH, CN, N<com:Sub>3< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, and C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is halogen. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is OH. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is methyl. In one aspect, the application relates to a compound of the application, <com:Math><semantics>e.g.<annotation encoding="application / x-tex">e.g.< / annotation>< / semantics>< / com:Math>, a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, Vla, Vlb, Vlc, Vld, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application for use in preventing or treating a disease or disorder in a subject in need thereof. In one aspect, the application relates to a compound of the application, e.g., a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, Vla, Vlb, Vlc, Vld, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application, for use in preventing or treating a disease or disorder in a subject in need thereof, wherein R<com:Sup>5< / com:Sup> is in the S-configuration. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, CONH<com:Sub>2< / com:Sub>, COOH, CN, N<com:Sub>3< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, and C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S- configuration and is selected from the group consisting of halogen, OH, and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is halogen. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is OH. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is methyl. One aspect of this application provides compounds that are useful for the treatment of diseases, disorders, and conditions characterized by excessive or abnormal cell proliferation. Such diseases include, but are not limited to, a proliferative or hyperproliferative disease. Examples of proliferative and hyperproliferative diseases include, without limitation, cancer. In one aspect, the disorder is proliferative disorder. In another aspect, the proliferative disorder is selected from a group consisting of a proliferative disorder of the skin, such as psoriasis and actinic keratosis. In another aspect, the proliferative disorder is selected from a group consisting of brain cancer, liver cancer, pancreatic cancer, gastric cancer, breast cancer, ovarian cancer, nerve cancer, bone cancer, cervical cancer, colorectal cancer, esophageal cancer, kidney cancer, lung cancer, muscle cancer, pharyngeal cancer, placental cancer, prostate cancer, skin cancer, soft tissue cancer, stomach cancer, thyroid cancer, tongue cancer, uterine cancer, bladder cancer, blood cancer, hematologic tumor, childhood leukemia, lymphoma, multiple myeloma, Hodgkin's disease, lymphoma of lymphocytic origin, lymphoma of cutaneous origin, acute leukemia, chronic leukemia, acute lymphoblastic leukemia, plasma cell neoplasm, lymphoid neoplasm, cancer associated with AIDS, acute myelocytic leukemia, chronic myelocytic leukemia, malignant melanoma, non-melanoma skin cancer, epidermic cyst, dermoid cyst, lipoma, adenoma, capillary or cutaneous hemangioma, lymphangioma, nevi lesion, teratoma, nephroma, myofibromatosis, osteoplastic tumor, dysplastic mass, and dysplasia. In one aspect, the disorder is cancer. In another aspect, the cancer is selected from a group consisting of bladder cancer, blood cancer, bone cancer, brain cancer, nerve cancer, breast cancer, cervical cancer, colorectal cancer, esophageal cancer, kidney cancer, lung cancer, muscle cancer, ovarian cancer, pancreatic cancer, pharyngeal cancer, placental cancer, prostate cancer, skin cancer, soft tissue cancer, stomach cancer, gastric cancer, thyroid cancer, tongue cancer, and uterine cancer. In another aspect, the cancer is brain cancer. In a further aspect, the brain cancer is glioblastoma. In one aspect, the application relates to a method of preventing or treating a brain cancer comprising administering to a subject in need thereof an effective amount of a compound of the application, e.g., a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, VIa, VIb, VIc, VId, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application. In one aspect, <com:Math><semantics>ℝ5<annotation encoding="application / x-tex">\mathbb{R}^5< / annotation>< / semantics>< / com:Math> is in the S-configuration. In one aspect, <com:Math><semantics>ℝ5<annotation encoding="application / x-tex">\mathbb{R}^5< / annotation>< / semantics>< / com:Math> is in the S-configuration and is selected from the group consisting of halogen, OH, CONH2, COOH, CN, N3, C1-C6 alkyl, C2-C6 alkenyl, and C2- C<com:Sub>6< / com:Sub> alkynyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is halogen. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is OH. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl. In one aspect, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is in the S-configuration and is methyl. In one aspect, the application relates to the use of a compound of the application, e.g., a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, VIa, VIb, VIc, VId, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application, for preventing or treating a brain cancer. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, CONH<com:Sub>2< / com:Sub>, COOH, CN, N<com:Sub>3< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, and C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S- configuration and is halogen. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is OH. In one aspect, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is in the S-configuration and is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl. In one aspect, <com:Math><semantics>R5<annotation encoding="application / x-tex">R^5< / annotation>< / semantics>< / com:Math> is in the S-configuration and is methyl. In one aspect, the application relates to the use of a compound of the application, <com:Math><semantics>e.g.<annotation encoding="application / x-tex">e.g.< / annotation>< / semantics>< / com:Math>, a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, VIa, VIb, VIc, VId, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application, in the manufacture of a medicament for preventing or treating a brain cancer. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, CONH<com:Sub>2< / com:Sub>, COOH, CN, N<com:Sub>3< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, and C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is halogen. In one aspect, R<com:Sup>5< / com:Sup> is in the S- configuration and is OH. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is methyl. In one aspect, the application relates to a compound of the application, e.g., a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, VIa, VIb, VIc, VId, VIIa, VIIb, VIIc, VIId, or VIIe or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or a pharmaceutical composition of the application, for use in preventing or treating a brain cancer. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, CONH<com:Sub>2< / com:Sub>, COOH, CN, N<com:Sub>3< / com:Sub>, C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl, C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkenyl, and C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> alkynyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is selected from the group consisting of halogen, OH, and C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> alkyl. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is halogen. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is OH. In one aspect, R<com:Sup>5< / com:Sup> is in the S-configuration and is <com:Math><semantics>C1<annotation encoding="application / x-tex">C_1< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math> alkyl. In one aspect, <com:Math><semantics>ℝ5<annotation encoding="application / x-tex">\mathbb{R}^5< / annotation>< / semantics>< / com:Math> is in the S-configuration and is methyl. In one aspect, the proliferative disorder is brain cancer. In another aspect, the brain cancer is a primary tumor. In another aspect, the primary brain tumor is selected from glioblastoma, astrocytoma, meningioma, pituitary adenoma, vestibular schwannoma, ependymoma, oligodendroglioma, choroid plexus papillomas, and medullablastoma. In one aspect, the disorder is angiogenic disorder. In another aspect, the angiogenic disorder is selected from cancer, wet macular degeneration, and dry macular degeneration. In one aspect, the disorder is abnormal vascularization. In one aspect, the disorder is ocular myopathy. In one aspect, the compound of the application or composition is administered orally, parenterally, subcutaneously, intravenously, intramuscularly, intraperitoneally, by intranasal instillation, by intracavitary or intravesical instillation, topically, intraarterially, intralesionally, by metering pump, or by application to mucous membranes. In another aspect, the compound of the application or composition is administered orally, parenterally, or intravenously. In one aspect, the compound of the application or composition is administered orally. Definitions For convenience, certain terms used in the specification, examples and appended claims are collected here. Protein kinases are a large class of enzymes which catalyze the transfer of the <com:Math><semantics>γ<annotation encoding="application / x-tex">\gamma< / annotation>< / semantics>< / com:Math>- phosphate from ATP to the hydroxyl group on the side chain of Ser / Thr or Tyr in proteins and peptides and are intimately involved in the control of various important cell functions, perhaps most notably: signal transduction, differentiation, and proliferation. There are estimated to be about 2,000 distinct protein kinases in the human body, and although each of these phosphorylates particular protein / peptide substrates, they all bind the same second substrate ATP in a highly conserved pocket. About 50% of the known oncogene products are protein tyrosine kinases (PTKs), and their kinase activity has been shown to lead to cell transformation. The PTKs can be classified into two categories, the membrane receptor PTKs (e.g., growth factor receptor PTKs) and the non-receptor PTKs (e.g., the Src family of proto-oncogene products and focal adhesion kinase (FAK)). The hyperactivation of Src has been reported in a number of human cancers, including those of the colon, breast, lung, bladder, and skin, as well as in gastric cancer, hairy cell leukemia, and neuroblastoma. The phrase "inhibits one or more components of a protein kinase signaling cascade" means that one or more components of the kinase signaling cascade are effected such that the function of the cell changes. Components of a protein kinase signaling cascade include any proteins involved directly or indirectly in the kinase signaling pathway including second messengers and upstream and downstream targets. "Treating", includes any effect, e.g., lessening, reducing, modulating, or eliminating, that results in the improvement of the condition, disease, disorder, etc. "Treating" or "treatment" of a disease state includes: (1) inhibiting the disease state, i.e., arresting the development of the disease state or its clinical symptoms; or (2) relieving the disease state, i.e., causing temporary or permanent regression of the disease state or its clinical symptoms. "Preventing", refers to causing the clinical symptoms of the disease state not to develop in a subject that may be exposed to or predisposed to the disease state, but does not yet experience or display symptoms of the disease state. As used herein, the term "proliferative disorder" refers to conditions in which the unregulated and / or abnormal growth of cells can lead to the development of an unwanted condition or disease, which can be cancerous or non-cancerous, for example a psoriatic condition. As used herein, the terms "psoriatic condition" or "psoriasis" refers to disorders involving keratinocyte hyperproliferation, inflammatory cell infiltration, and cytokine alteration. Exemplary cell proliferative disorder include, but are not limited to, neoplasms, benign tumors, malignant tumors, pre-cancerous conditions, in situ tumors, encapsulated tumors, metastatic tumors, liquid tumors, solid tumors, immunological tumors, hematological tumors, cancers, carcinomas, leukemias, lymphomas, sarcomas, and rapidly dividing cells. The term "rapidly dividing cell" as used herein is defined as any cell that divides at a rate that exceeds or is greater than what is expected or observed among neighboring or juxtaposed cells within the same tissue. A cell proliferative disorder includes a precancer or a precancerous condition. A cell proliferative disorder includes cancer. As used herein, the term "cancer" includes solid tumors, such as lung, breast, colon, ovarian, brain, liver, pancreas, prostate, malignant melanoma, non-melanoma skin cancers, as well as hematologic tumors and / or malignancies, such as childhood leukemia and lymphomas, multiple myeloma, Hodgkin's disease, lymphomas of lymphocytic and cutaneous origin, acute and chronic leukemia such as acute lymphoblastic, acute myelocytic or chronic myelocytic leukemia, plasma cell neoplasm, lymphoid neoplasm and cancers associated with AIDS. Cancer is a group of diseases that may cause almost any sign or symptom. The signs and symptoms will depend on where the cancer is, the size of the cancer, and how much it affects the nearby organs or structures. If a cancer spreads (metastasizes), then symptoms may appear in different parts of the body. Cancers include metastatic cancer, for example, cancer that has spread from the place where it first started to another place in the body. Exemplary cancers include, but are not limited to, adrenocortical carcinoma, AIDS- related cancers, AIDS-related lymphoma, anal cancer, anorectal cancer, cancer of the anal canal, appendix cancer, childhood cerebellar astrocytoma, childhood cerebral astrocytoma, basal cell carcinoma, skin cancer (non-melanoma), biliary cancer, extrahepatic bile duct cancer, intrahepatic bile duct cancer, bladder cancer, urinary bladder cancer, bone and joint cancer, osteosarcoma and malignant fibrous histiocytoma, brain cancer, brain tumor, brain stem glioma, cerebellar astrocytoma, cerebral astrocytoma / malignant glioma, ependymoma, medulloblastoma, supratentorial primitive neuroectodermal tumors, visual pathway and hypothalamic glioma, breast cancer, bronchial adenomas / carcinoids, carcinoid tumor, gastrointestinal, nervous system cancer, nervous system lymphoma, central nervous system cancer, central nervous system lymphoma, cervical cancer, childhood cancers, chronic lymphocytic leukemia, chronic myelogenous leukemia, chronic myeloproliferative disorders, colon cancer, colorectal cancer, cutaneous T-cell lymphoma, lymphoid neoplasm, mycosis fungoides, Seziary Syndrome, endometrial cancer, esophageal cancer, extracranial germ cell tumor, extragonadal germ cell tumor, extrahepatic bile duct cancer, eye cancer, intraocular melanoma, retinoblastoma, gallbladder cancer, gastric (stomach) cancer, gastrointestinal carcinoid tumor, gastrointestinal stromal tumor (GIST), germ cell tumor, ovarian germ cell tumor, gestational trophoblastic tumor glioma, head and neck cancer, hepatocellular (liver) cancer, Hodgkin lymphoma, hypopharyngeal cancer, intraocular melanoma, ocular cancer, islet cell tumors (endocrine pancreas), Kaposi Sarcoma, kidney cancer, renal cancer, kidney cancer, laryngeal cancer, acute lymphoblastic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, hairy cell leukemia, lip and oral cavity cancer, liver cancer, lung cancer, non-small cell lung cancer, small cell lung cancer, AIDS-related lymphoma, non-Hodgkin lymphoma, primary central nervous system lymphoma, Waldenstram macroglobulinemia, medulloblastoma, melanoma, intraocular (eye) melanoma, merkel cell carcinoma, mesothelioma malignant, mesothelioma, metastatic squamous neck cancer, mouth cancer, cancer of the tongue, multiple endocrine neoplasia syndrome, mycosis fungoides, myelodysplastic syndromes, myelodysplastic / myeloproliferative diseases, chronic myelogenous leukemia, acute myeloid leukemia, multiple myeloma, chronic myeloproliferative disorders, nasopharyngeal cancer, neuroblastoma, oral cancer, oral cavity cancer, oropharyngeal cancer, ovarian cancer, ovarian epithelial cancer, ovarian low malignant potential tumor, pancreatic cancer, islet cell pancreatic cancer, paranasal sinus and nasal cavity cancer, parathyroid cancer, penile cancer, pharyngeal cancer, pheochromocytoma, pineoblastoma and supratentorial primitive neuroectodermal tumors, pituitary tumor, plasma cell neoplasm / multiple myeloma, pleuropulmonary blastoma, prostate cancer, rectal cancer, renal pelvis and ureter, transitional cell cancer, retinoblastoma, rhabdomyosarcoma, salivary gland cancer, ewing family of sarcoma tumors, Kaposi Sarcoma, soft tissue sarcoma, uterine cancer, uterine sarcoma, skin cancer (non- melanoma), skin cancer (melanoma), merkel cell skin carcinoma, small intestine cancer, soft tissue sarcoma, squamous cell carcinoma, stomach (gastric) cancer, supratentorial primitive neuroectodermal tumors, testicular cancer, throat cancer, thymoma, thymoma and thymic carcinoma, thyroid cancer, transitional cell cancer of the renal pelvis and ureter and other urinary organs, gestational trophoblastic tumor, urethral cancer, endometrial uterine cancer, uterine sarcoma, uterine corpus cancer, vaginal cancer, vulvar cancer, and Wilm's Tumor. The term "brain cancer" encompasses a variety of cancers. There can be actual brain tumors which arise from the brain itself, known as primary brain cancers of which there are several. The term "brain cancer" refers to malignant tumors i.e., tumors that grow and spread aggressively, overpowering healthy cells by taking up their space, blood, and nutrients. Tumors that do not spread aggressively are called benign tumors. Benign tumors are generally less serious than a malignant tumor, but a benign tumor can still cause problems in the brain. There can also be brain metastases, which represent the spread of other cancers, such as lung or breast to the brain. Brain tumors are classified by both the cell of the brain that makes them up and how the tumor looks under the microscope. Primary brain tumors arise from any of the cells in the brain, or from specific structures in the brain. Glia cells support the neurons of the brain and tumors which arise from these cells are known as glial tumors. The membrane that surrounds the brain can also develop tumors and these are known as meningiomas. There are other types of tumors, which involve other structures of the brain including ependymoma. The most common primary brain tumors are gliomas, meningiomas, pituitary adenomas, vestibular schwannomas, and primitive neuroectodermal tumors (medullablastomas). Glioblastoma is a malignant rapidly growing astrocytoma of the central nervous system and usually of a cerebral hemisphere. Synonyms for glioblastoma include glioblastoma multiforme (GBM), giant cell glioblastoma, and multiforme spongioblastoma multiforme. Glioblastoma is the most common malignant primary brain tumor and has proven very difficult to treat. These tumors are often aggressive and infiltrate surrounding brain tissue. Glioblastomas arise from glial cells, which are cells that form the tissue that surrounds and protects other nerve cells found within the brain and spinal cord. Glioblastomas are mainly composed of star-shaped glial cells known as astrocytes. The term "glioma" includes any type of brain tumor such as astrocytomas, oligodendrogliomas, ependymomas, and choroid plexus papillomas. Astrocytomas come in four grades based on how fast the cells are reproducing and the likelihood that they will infiltrate nearby tissue. Grades I or II astrocytomas are nonmalignant and may be referred to as low-grade. Grades III and IV astrocytomas are malignant and may be referred to as high-grade astrocytomas. Grade II astrocytomas are known as anaplastic astrocytomas. Grade IV astrocytomas are known as glioblastoma multiforme. Medulloblastoma is a highly malignant primary brain tumor that originates in the cerebellum or posterior fossa. Originally considered to be a glioma, medulloblastoma is now known to be of the family of cranial primitive neuroectodermal tumors (PNET). Tumors that originate in the cerebellum are referred to as infratentorial because they occur below the tentorium, a thick membrane that separates the cerebral hemispheres of the brain from the cerebellum. Another term for medulloblastoma is infratentorial PNET. Medulloblastoma is the most common PNET originating in the brain. All PNET tumors of the brain are invasive and rapidly growing tumors that, unlike most brain tumors, spread through the cerebrospinal fluid (CSF) and frequently metastasize to different locations in the brain and spine. The peak of occurrence of medullablastoma is seven years of age. Seventy percent of medulloblastomas occur in individuals younger than 16. Desmoplastic medulloblastoma is encountered especially in adulthood. This type of tumor rarely occurs beyond the fifth decade of life. Neuroblastoma is a cancer that forms in nerve tissue. The cells of neuroblastoma usually resemble very primitive developing nerve cells found in an embryo or fetus. The term neuro indicates "nerves," while blastoma refers to a cancer that affects immature or developing cells. Neurons (nerve cells) are the main component of the brain and spinal cord and of the nerves that connect them to the rest of the body. Neuroblastoma usually begins in the adrenal glands, but it may also begin in the spinal cord. Neuroblastoma is the most common extracranial solid cancer in childhood. In 2007, neuroblastoma was the most common cancer in infancy, with an annual incidence of about 650 new cases per year in the US. Close to 50 percent of neuroblastoma cases occur in children younger than two years old. It is a neuroendocrine tumor, arising from any neural crest element of the sympathetic nervous system or SNS. A branch of the autonomic nervous system, the SNS is a nerve network that carries messages from the brain throughout the body and is responsible for the fight-or-flight response and production of adrenaline or epinephrine. Neuroepithelioma is malignant tumors of the neuroepithelium. Neuroepithelioma is found most commonly in children and young adults. It arises most often in the chest wall, pelvis, or extremity, either in bone or soft tissue. Procedures used in the diagnosis may include blood and urine tests, X rays of the affected bone and the whole body and lungs, bone marrow aspirations, CT scans, and fluoroscopy. Treatments include surgery, radiation therapy and chemotherapy. Ewing's tumors are an example of a type of peripheral neuroepithelioma. In addition to psoriatic conditions, the types of proliferative diseases which may be treated using the compositions of the present application are epidermic and dermoid cysts, lipomas, adenomas, capillary and cutaneous hemangiomas, lymphangiomas, nevi lesions, teratomas, nephromas, myofibromatosis, osteoplastic tumors, and other dysplastic masses and the like. The proliferative diseases can include dysplasias and disorders of the like. The term "angiogenic disorder" refers to conditions in which the unregulated and / or abnormal growth of blood vessels can lead to development of unwanted condition or disease, which can be cancerous or non-cancerous, for example, wet and dry macular degeneration. An "effective amount" of a compound of the disclosed application is the quantity which, when administered to a subject having a disease or disorder, results in regression of the disease or disorder in the subject. Thus, an effective amount of a compound of the disclosed application is the quantity which, when administered to a subject having a cell proliferation disorder, results in regression of cell growth in the subject. The amount of the disclosed compound to be administered to a subject will depend on the particular disorder, the mode of administration, co-administered compounds, if any, and the characteristics of the subject, such as general health, other diseases, age, sex, genotype, body weight and tolerance to drugs. The skilled artisan will be able to determine appropriate dosages depending on these and other factors. As used herein, the term "effective amount" refers to an amount of a compound, or a combination of compounds, of the present application effective when administered alone or in combination as an anti-proliferative agent. For example, an effective amount refers to an amount of the compound present in a formulation or on a medical device given to a recipient patient or subject sufficient to elicit biological activity, for example, anti-proliferative activity, such as e.g., anti-cancer activity or anti-neoplastic activity. The combination of compounds optionally is a synergistic combination. Synergy, as described, for example, by Chou and Talalay, Adv. Enzyme Regul. vol. 22, pp. 27-55 (1984), occurs when the effect of the compounds when administered in combination is greater than the additive effect of the compounds when administered alone as a single agent. In general, a synergistic effect is most clearly demonstrated at sub-optimal concentrations of the compounds. Synergy can be in terms of lower cytotoxicity, or increased anti-proliferative effect, or some other beneficial effect of the combination compared with the individual components. The term "compounds of the application" or "a compound of the application" refers to a compound according to formula A, I, II, III, IVa, IVb, IVc, IVd, Va, Vb, Vc, Vd, VIa, VIb, VIc, VId, VIIa, VIIb, VIIc, VIId, or VIIe or any specific compound described herein (e.g., a compound in Table 1). Compound X is of the following structure: () Compound Y is of the following structure: [Image disponible dans le document PDF, Image available in the PDF document] With respect to the chemical compounds useful in the present application, the following terms can be applicable: The term "substituted," as used herein, means that any one or more hydrogens on the designated atom is replaced with a selection from the indicated group, provided that the designated atom's normal valency is not exceeded, and that the substitution results in a stable compound. When a substituent is keto <com:Math><semantics>(i.e.,=0)<annotation encoding="application / x-tex">(i.e., =0)< / annotation>< / semantics>< / com:Math>, then 2 hydrogens on the atom are replaced. Keto substituents are not present on aromatic moieties. Ring double bonds, as used herein, are double bonds that are formed between two adjacent ring atoms (e.g., C=C, C=N, or N=N). The present application is intended to include all isotopes of atoms occurring in the present compounds. Isotopes include those atoms having the same atomic number but different mass numbers. By way of general example and without limitation, isotopes of hydrogen include tritium and deuterium, and isotopes of carbon include C-13 and C-14. The compounds described herein may have asymmetric centers. Compounds of the present application containing an asymmetrically substituted atom may be isolated in optically active or racemic forms. It is well known in the art how to prepare optically active forms, such as by resolution of racemic forms or by synthesis from optically active starting materials. Many geometric isomers of olefins, C=N double bonds, and the like can also be present in the compounds described herein, and all such stable isomers are contemplated in the present application. Cis and trans geometric isomers of the compounds of the present application are described and may be isolated as a mixture of isomers or as separated isomeric forms. All chiral, diastereomeric, racemic, and geometric isomeric forms of a structure are intended, unless the specific stereochemistry or isomeric form is specifically indicated. All tautomers of shown or described compounds are also considered to be part of the present application. When any variable (e.g., R<com:Sub>5< / com:Sub>) occurs more than one time in any constituent or formula for a compound, its definition at each occurrence is independent of its definition at every other occurrence. Thus, for example, if a group is shown to be substituted with 0-2 R<com:Sub>5< / com:Sub> moieties, then the group may optionally be substituted with up to two R<com:Sub>5< / com:Sub> moieties and R<com:Sub>5< / com:Sub> at each occurrence is selected independently from the definition of R<com:Sub>5< / com:Sub>. Also, combinations of substituents and / or variables are permissible, but only if such combinations result in stable compounds. When a bond to a substituent is shown to cross a bond connecting two atoms in a ring, then such substituent may be bonded to any atom in the ring. When a substituent is listed without indicating the atom via which such substituent is bonded to the rest of the compound of a given formula, then such substituent may be bonded via any atom in such substituent. Combinations of substituents and / or variables are permissible, but only if such combinations result in stable compounds. Compounds of the present application that contain nitrogens can be converted to N- oxides by treatment with an oxidizing agent (e.g., 3-chloroperoxybenzoic acid (m-CPBA) and / or hydrogen peroxides) to afford other compounds of the present application. Thus, all shown and claimed nitrogen-containing compounds are considered, when allowed by valency and structure, to include both the compound as shown and its N-oxide derivative (which can be designated as <com:Math><semantics>N→O<annotation encoding="application / x-tex">N\rightarrow O< / annotation>< / semantics>< / com:Math> or <com:Math><semantics>N+−O−<annotation encoding="application / x-tex">N^+-O^-< / annotation>< / semantics>< / com:Math>). Furthermore, in other instances, the nitrogens in the compounds of the present application can be converted to N-hydroxy or N-alkoxy compounds. For example, N-hydroxy compounds can be prepared by oxidation of the parent amine by an oxidizing agent such as m-CPBA. All shown and claimed nitrogen-containing compounds are also considered, when allowed by valency and structure, to cover both the compound as shown and its N-hydroxy (i.e., N-OH) and N-alkoxy (i.e., N-OR, wherein R is substituted or unsubstituted <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl, C<com:Sub>1-6< / com:Sub> alkenyl, C<com:Sub>1-6< / com:Sub> alkynyl, C<com:Sub>3-14< / com:Sub> carbocycle, or 3-14-membered heterocycle) derivatives. When an atom or chemical moiety is followed by a subscripted numeric range (e.g., <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math>), the application is meant to encompass each number within the range as well as all intermediate ranges. For example, "C<com:Sub>1-6< / com:Sub> alkyl" is meant to include alkyl groups with 1, 2, 3, 4, 5, 6, 1-6, 1-5, 1-4, 1-3, 1-2, 2-6, 2-5, 2-4, 2-3, 3-6, 3-5, 3-4, 4-6, 4-5, and 5-6 carbons. As used herein, "alkyl" is intended to include both branched and straight-chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms. For example, <com:Math><semantics>C1−6<annotation encoding="application / x-tex">C_{1-6}< / annotation>< / semantics>< / com:Math> alkyl is intended to include C1, C2, C3, C4, C5, and C6 alkyl groups. Examples of alkyl include, but are not limited to, methyl, ethyl, n-propyl, i-propyl, n-butyl, s-butyl, t-butyl, n-pentyl, s-pentyl, and n-hexyl. "Alkyl" further includes alkyl groups that have oxygen, nitrogen, sulfur or phosphorous atoms replacing one or more hydrocarbon backbone carbon atoms. In certain embodiments, a straight chain or branched chain alkyl has six or fewer carbon atoms in its backbone (e.g., C<com:Sub>1< / com:Sub>-C<com:Sub>6< / com:Sub> for straight chain, C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub> for branched chain), and in another embodiment, a straight chain or branched chain alkyl has four or fewer carbon atoms. "Substituted alkyl" refers to alkyl moieties having substituents replacing one or more hydrogen on one or more carbons of the hydrocarbon backbone. Such substituents can include, for example, alkyl, alkenyl, alkynyl, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkylamino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety. "Cycloalkyl" refers to cyclic moieties having 3 to 14 carbon atoms in their ring structure. In another embodiment, cycloalkyls have 3 to 8 carbon atoms in their ring structure. In another embodiment, cycloalkyls have 5 or 6 carbons in the ring structure. Cycloalkyls can be further substituted, e.g., with the substituents described above. "Alkenyl" includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double bond. For example, the term "alkenyl" includes straight-chain alkenyl groups (e.g., ethenyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, nonenyl, decenyl), branched-chain alkenyl groups, alkyl or alkenyl substituted cycloalkenyl groups, and cycloalkyl or cycloalkenyl substituted alkenyl groups. The term "alkenyl" further includes alkenyl groups, which include oxygen, nitrogen, sulfur or phosphorous atoms replacing one or more hydrocarbon backbone carbons. In certain embodiments, a straight chain or branched chain alkenyl group has six or fewer carbon atoms in its backbone (e.g., C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub> for straight chain, C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub> for branched chain). The term "C<com:Sub>2< / com:Sub>- <com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>" includes alkenyl groups containing two to six carbon atoms. The term "<com:Math><semantics>C3<annotation encoding="application / x-tex">C_3< / annotation>< / semantics>< / com:Math>-<com:Math><semantics>C6<annotation encoding="application / x-tex">C_6< / annotation>< / semantics>< / com:Math>" includes alkenyl groups containing three to six carbon atoms. "Substituted alkenyl" refers to alkenyl moieties having substituents replacing one or more hydrogen on one or more hydrocarbon backbone carbon atoms. Such substituents can include, for example, alkyl groups, alkynyl groups, halogens, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkylamino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety. "Cycloalkenyl," e.g., cyclopropenyl, cyclopentenyl, cyclohexenyl, cycloheptenyl, cyclooctenyl, refers to cyclic moieties having 3 to 14 carbon atoms in their ring structure and at least one double bond. In another emodiment cycloalkenyls may have from 3 to 8 carbon atoms in their ring structure. In another emodiment cycloalkenyl groups may have 5 or 6 carbons in the ring structure. Cycloalkenyls can be further substituted, e.g., with the substituents described above. "Alkynyl" includes unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but which contain at least one triple bond. For example, "alkynyl" includes straight-chain alkynyl groups (e.g., ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, decynyl), branched-chain alkynyl groups, and cycloalkyl or cycloalkenyl substituted alkynyl groups. The term "alkynyl" further includes alkynyl groups having oxygen, nitrogen, sulfur or phosphorous atoms replacing one or more hydrocarbon backbone carbons. In certain embodiments, a straight chain or branched chain alkynyl group has six or fewer carbon atoms in its backbone (e.g., C2-C6 for straight chain, C4-C6 for branched chain). The term "C<com:Sub>2< / com:Sub>-C<com:Sub>6< / com:Sub>" includes alkynyl groups containing two to six carbon atoms. The term "C<com:Sub>3< / com:Sub>-C<com:Sub>6< / com:Sub>" includes alkynyl groups containing three to six carbon atoms. "Substituted alkynyl" refers to alkynyl moieties having substituents replacing a hydrogen on one or more hydrocarbon backbone carbon atoms. Such substituents can include, for example, alkyl groups, alkynyl groups, halogens, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylaminocarbonyl, dialkylaminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkylamino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety. "Cycloalkynyl," e.g., cyclooctynyl, refers to cyclic moieties having 8 to 14 carbon atoms in their ring structure and at least one triple bond. In one emodiment the cycloalkynyl moiety may have 8 or 9 carbons in the ring structure. Cycloalkynyls can be further substituted, e.g., with the substituents described above. Unless the number of carbons is otherwise specified, "lower alkyl" includes an alkyl group, as defined above, but having from one to ten, or in another embodiment from one to six, carbon atoms in its backbone structure. "Lower alkenyl" and "lower alkynyl" have chain lengths of, for example, 2-6 carbon atoms. An "alkylaryl" or an "aralkyl" moiety is an alkyl substituted with an aryl (e.g., phenylmethyl (benzyl)). "Aryl" includes groups with aromaticity, including 5- and 6-membered "unconjugated", or single-ring, aromatic groups that may include from zero to four heteroatoms, as well as "conjugated", or multicyclic, systems with at least one aromatic ring. Examples of aryl groups include benzene, phenyl, pyrrole, furan, thiophene, thiazole, isothiazole, imidazole, triazole, tetrazole, pyrazole, oxazole, isooxazole, pyridine, pyrazine, pyridazine, and pyrimidine, and the like. Furthermore, the term "aryl" includes multicyclic aryl groups, e.g., tricyclic, bicyclic, e.g., naphthalene, benzoxazole, benzodioxazole, benzothiazole, benzoimidazole, benzothiophene, methylenedioxyphenyl, quinoline, isoquinoline, napthridine, indole, benzofuran, purine, benzofuran, deazapurine, or indolizine. Those aryl groups having heteroatoms in the ring structure may also be referred to as "aryl heterocycles", "heterocycles," "heteroaryls" or "heteroaromatics". The aromatic ring can be substituted at one or more ring positions with such substituents as described above, as for example, halogen, hydroxyl, alkoxy, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkylaminocarbonyl, aralkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, alkenylcarbonyl, alkoxycarbonyl, aminocarbonyl, alkylthiocarbonyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkylamino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkylaryl, or an aromatic or heteroaromatic moiety. Aryl groups can also be fused or bridged with alicyclic or heterocyclic rings, which are not aromatic so as to form a multicyclic system (e.g., tetralin, methylenedioxyphenyl). As used herein, "halo" or "halogen" refers to fluoro, chloro, bromo, and iodo. The term "perhalogenated" generally refers to a moiety wherein all hydrogens are replaced by halogen atoms. The term "haloalkyl" refers to both branched and straight—chain saturated aliphatic hydrocarbon groups having the specified number of carbon atoms, substituted with 1 or more halogen (for example <com:Math><semantics>−CVFW<annotation encoding="application / x-tex">-C_VF_W< / annotation>< / semantics>< / com:Math> wherein <com:Math><semantics>v=1<annotation encoding="application / x-tex">v = 1< / annotation>< / semantics>< / com:Math> to 3 and <com:Math><semantics>w=1<annotation encoding="application / x-tex">w = 1< / annotation>< / semantics>< / com:Math> to <com:Math><semantics>(2v+1)<annotation encoding="application / x-tex">(2v+1)< / annotation>< / semantics>< / com:Math>). Examples of haloalkyl include, but are not limited to, trifluoromethyl, trichloromethyl, pentafluoroethyl, and pentachloroethyl. The term "non-hydrogen substituent" refers to substituents other than hydrogen. Non- limiting examples include alkyl groups, alkoxy groups, halogen groups, hydroxyl groups, aryl groups, etc. As used herein, "carbocycle" or "carbocyclic ring" is intended to mean any stable monocyclic, bicyclic, or tricyclic ring having the specified number of carbons, any of which may be saturated, unsaturated, or aromatic. For example a <com:Math><semantics>C3−14<annotation encoding="application / x-tex">C_{3-14}< / annotation>< / semantics>< / com:Math> carbocycle is intended to mean a mono-, bi-, or tricyclic ring having 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, or 14 carbon atoms. Examples of carbocycles include, but are not limited to, cyclopropyl, cyclobutyl, cyclobutenyl, cyclopentyl, cyclopentenyl, cyclohexyl, cycloheptenyl, cycloheptyl, cycloheptenyl, adamantyl, cyclooctyl, cyclooctenyl, cyclooctynyl, cyclooctadienyl, fluorenyl, phenyl, naphthyl, indanyl, adamantyl, and tetrahydronaphthyl. Bridged rings are also included in the definition of carbocycle, including, for example, [3.3.0]bicyclooctane, [4.3.0]bicyclononane, [4.4.0]bicyclodecane, and [2.2.2]bicyclooctane. A bridged ring occurs when one or more carbon atoms link two non-adjacent carbon atoms. In one embodiment, bridge rings are one or two carbon atoms. It is noted that a bridge always converts a monocyclic ring into a tricyclic ring. When a ring is bridged, the substituents recited for the ring may also be present on the bridge. Fused (e.g., naphthyl and tetrahydronaphthyl) and spiro rings are also included. As used herein, the term "heterocycle" or "heterocyclic" is intended to mean any stable monocyclic, bicyclic, or tricyclic ring which is saturated, unsaturated, or aromatic and comprises carbon atoms and one or more ring heteroatoms, e.g., 1 or 1-2 or 1-3 or 1-4 or 1-5 or 1-6 heteroatoms, independently selected from the group consisting of nitrogen, oxygen, and sulfur. A bicyclic or tricyclic heterocycle may have one or more heteroatoms located in one ring, or the heteroatoms may be located in more than one ring. The nitrogen and sulfur heteroatoms may optionally be oxidized (i.e., N<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math>O and S(O)<com:Sub>p< / com:Sub>, where p = 1 or 2). When a nitrogen atom is included in the ring it is either N or NH, depending on whether or not the nitrogen atom is attached to a double bond in the ring (i.e., a hydrogen is present if needed to maintain the tri- valency of the nitrogen atom). The nitrogen atom may be substituted or unsubstituted (i.e., N or NR wherein R is H or another substituent, as defined). The heterocyclic ring may be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure. The heterocyclic rings described herein may be substituted on carbon or on a nitrogen atom if the resulting compound is stable. A nitrogen in the heterocycle may optionally be quaternized. In one embodiment, when the total number of S and O atoms in the heterocycle exceeds 1, then these heteroatoms are not adjacent to one another. Bridged rings are also included in the definition of heterocycle. A bridged ring occurs when one or more atoms (i.e., C, O, N, or S) link two non-adjacent carbon or nitrogen atoms. Bridges include, but are not limited to, one carbon atom, two carbon atoms, one nitrogen atom, two nitrogen atoms, and a carbon-nitrogen group. It is noted that a bridge always converts a monocyclic ring into a tricyclic ring. When a ring is bridged, the substituents recited for the ring may also be present on the bridge. Spiro and fused rings are also included. As used herein, the term "aromatic heterocycle" or "heteroaryl" is intended to mean a stable 5, 6, or 7-membered monocyclic or bicyclic aromatic heterocyclic ring or 7, 8, 9, 10, 11, or 12-membered bicyclic aromatic heterocyclic ring which consists of carbon atoms and one or more heteroatoms, e.g., 1 or 1-2 or 1-3 or 1-4 or 1-5 or 1-6 heteroatoms, independently selected from the group consisting of nitrogen, oxygen, and sulfur. In the case of bicyclic heterocyclic aromatic rings, only one of the two rings needs to be aromatic (e.g., 2,3-dihydroindole), though both may be (e.g., quinoline). The second ring can also be fused or bridged as defined above for heterocycles. The nitrogen atom may be substituted or unsubstituted (i.e., N or NR wherein R is H or another substituent, as defined). The nitrogen and sulfur heteroatoms may optionally be oxidized (i.e., N<com:Math><semantics>→<annotation encoding="application / x-tex">\rightarrow< / annotation>< / semantics>< / com:Math>O and S(O)<com:Sub>p< / com:Sub>, where p = 1 or 2). It is to be noted that total number of S and O atoms in the aromatic heterocycle is not more than 1. Examples of heterocycles include, but are not limited to, acridinyl, azocinyl, benzimidazolyl, benzofuranyl, benzothiofuranyl, benzothiophenyl, benzoxazolyl, benzoxazolinyl, benzthiazolyl, benztriazolyl, benztetrazolyl, benzisoxazolyl, benzisothiazolyl, benzimidazolinyl, carbazolyl, 4aH-carbazolyl, carbolinyl, chromanyl, chromenyl, cinnolinyl, decahydroquinolinyl, <com:Math><semantics>2H,6H−1,5,2<annotation encoding="application / x-tex">2H,6H-1,5,2< / annotation>< / semantics>< / com:Math>-dithiazinyl, dihydrofuro[2,3-b]tetrahydrofuran, furanyl, furazanyl, imidazolidinyl, imidazolinyl, imidazolyl, 1H-indazolyl, indolenyl, indolinyl, indolizinyl, indolyl, 3H-indolyl, isatinoyl, isobenzofuranyl, isochromanyl, isoindazolyl, isoindolinyl, isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, methylenedioxyphenyl, morpholinyl, naphthyridinyl, octahydroisoquinolinyl, oxadiazolyl, 1,2,3-oxadiazolyl, 1,2,4- oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl, 1,2,4-oxadiazol5(4H)-one, oxazolidinyl, oxazolyl, oxindolyl, pyrimidinyl, phenanthridinyl, phenanthrolinyl, phenazinyl, phenothiazinyl, phenoxathinyl, phenoxazinyl, phthalazinyl, piperazinyl, piperidinyl, piperidonyl, 4-piperidonyl, piperonyl, pteridinyl, purinyl, pyranyl, pyrazinyl, pyrazolidinyl, pyrazolinyl, pyrazolyl, pyridazinyl, pyridooxazole, pyridoimidazole, pyridothiazole, pyridinyl, pyridyl, pyrimidinyl, pyrrolidinyl, pyrrolinyl, 2H-pyrrolyl, pyrrolyl, quinazolinyl, quinolinyl, 4H-quinolizinyl, quinoxalinyl, quinuclidinyl, tetrahydrofuranyl, tetrahydroisoquinolinyl, tetrahydroquinolinyl, tetrazolyl, 6H-1,2,5-thiadiazinyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,2,5-thiadiazolyl, 1,3,4- thiadiazolyl, thianthrenyl, thiazolyl, thienyl, thienothiazolyl, thienooxazolyl, thienoimidazolyl, thiophenyl, triazinyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,2,5-triazolyl, 1,3,4-triazolyl, and xanthenyl. The term "hydroxy" or "hydroxyl" includes groups with an -OH or -O<com:Sup>-< / com:Sup>. "Polycyclyl" or "polycyclic radical" refers to two or more cyclic rings (e.g., cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and / or heterocyclyls) in which two or more carbons are common to two adjoining rings. Rings that are joined through non-adjacent atoms are termed "bridged" rings. Each of the rings of the polycycle can be substituted with such substituents as described above, as for example, halogen, hydroxyl, alkylcarbonyloxy, arylcarbonyloxy, alkoxycarbonyloxy, aryloxycarbonyloxy, carboxylate, alkylcarbonyl, alkoxycarbonyl, alkylaminocarbonyl, aralkylaminocarbonyl, alkenylaminocarbonyl, alkylcarbonyl, arylcarbonyl, aralkylcarbonyl, alkenylcarbonyl, aminocarbonyl, alkylthiocarbonyl, alkoxyl, phosphate, phosphonato, phosphinato, cyano, amino (including alkylamino, dialkylamino, arylamino, diarylamino, and alkylarylamino), acylamino (including alkylcarbonylamino, arylcarbonylamino, carbamoyl and ureido), amidino, imino, sulfhydryl, alkylthio, arylthio, thiocarboxylate, sulfates, alkylsulfinyl, sulfonato, sulfamoyl, sulfonamido, nitro, trifluoromethyl, cyano, azido, heterocyclyl, alkyl, alkylaryl, or an aromatic or heteroaromatic moiety. In the present specification, the structural formula of the compound represents a certain isomer for convenience in some cases, but the present application includes all isomers such as geometrical isomer, optical isomer based on an asymmetrical carbon, stereoisomer, tautomer and the like which occur structurally and an isomer mixture and is not limited to the description of the formula for convenience, and may be any one of isomer or a mixture. Therefore, an asymmetrical carbon atom may be present in the molecule and an optically active compound and a racemic compound may be present in the present compound, but the present application is not limited to them and includes any one. In addition, a crystal polymorphism may be present but is not limiting, but any crystal form may be single or a crystal form mixture, or an anhydride or hydrate. Further, so-called metabolite which is produced by degradation of the present compound in vivo is included in the scope of the present application. "Isomerism" means compounds that have identical molecular formulae but that differ in the nature or the sequence of bonding of their atoms or in the arrangement of their atoms in space. Isomers that differ in the arrangement of their atoms in space are termed "stereoisomers". Stereoisomers that are not mirror images of one another are termed "diastereoisomers", and stereoisomers that are non-superimposable mirror images are termed "enantiomers", or sometimes optical isomers. A carbon atom bonded to four nonidentical substituents is termed a "chiral center". "Chiral isomer" means a compound with at least one chiral center. It has two enantiomeric forms of opposite chirality and may exist either as an individual enantiomer or as a mixture of enantiomers. A mixture containing equal amounts of individual enantiomeric forms of opposite chirality is termed a "racemic mixture". A compound that has more than one chiral center has 2<com:Sup>n-1< / com:Sup>enantiomeric pairs, where n is the number of chiral centers. Compounds with more than one chiral center may exist as either an individual diastereomer or as a mixture of diastereomers, termed a "diastereomeric mixture". When one chiral center is present, a stereoisomer may be characterized by the absolute configuration (R or S) of that chiral center. Absolute configuration refers to the arrangement in space of the substituents attached to the chiral center. The substituents attached to the chiral center under consideration are ranked in accordance with the Sequence Rule of Cahn, Ingold and Prelog. (Cahn et al, Angew. Chem. Inter. Edit. 1966, 5, 385; errata 511; Cahn et al., Angew. Chem. 1966, 78, 413; Cahn and Ingold, J. Chem. Soc. 1951 (London), 612; Cahn et al., Experientia 1956, 12, 81; Cahn, J., Chem. Educ. 1964, 41, 116). "Enantiomerically pure" or "enantiopure" refers to a sample of a chiral substance all of whose molecules (within the limits of detection) have the same chirality sense. In one aspect, a compound of the application is in an enantiopure form, such as in about 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 97%, 97%, 98%, 99%, or greater than 99% enantiomeric excess. In another aspect, the enantiomeric excess is about 90%, 95%, 97%, 99%, or greater than 99%. In another aspect, the enantiomeric excess is about 95%, 97%, 99%, or greater than 99%. In another aspect, the enantiomeric excess is about 99% or greater than 99%. In another aspect, In another aspect, the enantiomeric excess is about greater than 99%. "Enantiomeric excess" or "ee" refers to a measure for how much of one enantiomer is present compared to the other. For a mixture of R and S enantiomers, the percent enantiomeric excess is defined as |R-S|*100, where R and S are the respective mole or weight fractions of enantiomers in a mixture such that <com:Math><semantics>R+S=1<annotation encoding="application / x-tex">R+S=1< / annotation>< / semantics>< / com:Math>. With knowledge of the optical rotation of a chiral substance, the percent enantiomeric excess is defined as <com:Math><semantics>([α]obs / [α]max)*100<annotation encoding="application / x-tex">([\alpha]_{obs} / [\alpha]_{max})*100< / annotation>< / semantics>< / com:Math>, where <com:Math><semantics>[α]obs<annotation encoding="application / x-tex">[\alpha]_{obs}< / annotation>< / semantics>< / com:Math> is the optical rotation of the mixture of enantiomers and <com:Math><semantics>[α]max<annotation encoding="application / x-tex">[\alpha]_{max}< / annotation>< / semantics>< / com:Math> is the optical rotation of the pure enantiomer. Determination of enantiomeric excess is possible using a variety of analytical techniques, including NMR spectroscopy, chiral column chromatography or optical polarimetry. "Geometric Isomers" means the diastereomers that owe their existence to hindered rotation about double bonds. These configurations are differentiated in their names by the prefixes cis and trans, or Z and E, which indicate that the groups are on the same or opposite side of the double bond in the molecule according to the Cahn-Ingold-Prelog rules. Further, the structures and other compounds discussed in this application include all atropic isomers thereof. "Atropic isomers" are a type of stereoisomer in which the atoms of two isomers are arranged differently in space. Atropic isomers owe their existence to a restricted rotation caused by hindrance of rotation ...

Claims

1. A compound of formula (A): [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt, or solvate thereof, wherein: X a is CR a or N; X b is CR b or N; X c is CR c or N; X d is CR d or N; R a is H, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl; R b is H, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl; R c is H, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl; R d is H, halogen, C 1 -C 6 alkyl, C 2 -C 6 alkenyl, or C 2 -C 6 alkynyl; R 1 R^1 and R 2 R^2 are each independently H, C 1 C_1 - C 6 C_6 alkyl, C 2 C_2 - C 6 C_6 alkenyl, C 2 C_2 - C 6 C_6 alkynyl, or O-( C 1 C_1 - C 6 alkyl); alternatively, R 1 and R 2 , together with the carbon atom to which they are attached, form a 3-8 membered saturated, unsaturated, or partially saturated carbocycle, or a saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-7 membered rings and one or more heteroatoms selected from N, O, and S; alternatively, one of R 1 and R 2 , together with the carbon atom to which R 1 or R 2 is attached and (B), form a 7-12 membered saturated, unsaturated, or partially saturated carbocycle, or a 7-12 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S; R 3 and R 4 are each independently (a) H, (b) halogen, (c) OH, (d) COOH, (e) CONH 2 , (f) N H C O R 101 , ( g ) N R 101 C O R 102 , ( h ) S ( O ) t R 101 , ( i ) C 1 − C 6 a l k y l , ( j ) C 2 − C 6 a l k e n y l , ( k ) C 2 − C 6 a l k y n y l , ( k ) C 3 − C 6 a l k y n y l , ( k ) C 4 − C 6 a l k y n y l , ( k ) C 5 − C 6 a l k y n y l , NHCOR^{101}, (g) \ NR^{101}COR^{102}, (h) \ S(O)_t R^{101}, (i) \ C_1 - C_6 \ alkyl, (j) \ C_2 - C_6 \ alkenyl, (k) \ C_2 - C_6 \ alkynyl, (k) \ C_3 - C_6 \ alkynyl, (k) \ C_4 - C_6 \ alkynyl, (k) \ C_5 - C_6 \ alkynyl, (l) O-( C 1 C_1 - C 6 C_6 alkyl), (m) O-( C 2 C_2 - C 6 C_6 alkenyl), (n) O-( C 2 C_2 - C 6 C_6 alkynyl), (o) COO-( C 1 C_1 - C 6 C_6 alkyl), (p) COO-(C 2 -C 6 alkenyl), (q) COO-(C 2 -C 6 alkynyl), (r) CONH-(C 1 -C 6 alkyl), (s) CONH-(C 2 -C 6 alkenyl), (t) CONH-( C 2 C_2 - C 6 C_6 alkynyl), (u) CON( C 1 C_1 - C 6 C_6 alkyl) 2 , (v) CON( C 2 C_2 - C 6 C_6 alkenyl) 2 , (w) C O N ( C 2 − C 6 alkynyl ) 2 CON(C_2-C_6 \text{ alkynyl})_2 , (x) ( C 1 − C 6 alkyl ) u − N H 2 (C_1-C_6 \text{ alkyl})_u-NH_2 , (y) ( C 2 − C 6 alkenyl ) u − N H 2 (C_2-C_6 \text{ alkenyl})_u-NH_2 , (z) ( C 2 − C 6 alkynyl ) u − N H 2 (C_2-C_6 \text{ alkynyl})_u-NH_2 N H 2 NH_2 , (aa1) (C 1 -C 6 alkyl) v - N H NH (C 1 -C 6 alkyl), (aa2) (C 1 -C 6 alkyl) v - N H NH (C 2 -C 6 alkenyl), (aa3) (C 1 - C 6 C_6 alkyl) v -NH( C 2 C_2 - C 6 C_6 alkynyl), (bb1) ( C 2 C_2 - C 6 C_6 alkenyl) v -NH( C 1 C_1 - C 6 C_6 alkyl), (bb2) ( C 2 C_2 - C 6 C_6 alkenyl) v - <Formule mathématique disponible dans le document PDF, Math available in the PDF document>NH(C_2-C_6 \text{ alkenyl}), (bb3) (C_2-C_6 \text{ alkenyl})_v-NH(C_2-C_6 \text{ alkynyl}), (cc1) (C_2-C_6 \text{ alkynyl})_v-NH(C_1-C_6 \text{ alkenyl}), (cc1) (cc1) (cc2-cc6 \text{ alkynyl})_v-NH(cc2-cc6 \text{ alkynyl}), (cc1) (cc2-cc6 \text{ alkyny alkyl), (cc2) ( C 2 C_2 - C 6 C_6 alkynyl) v -NH( C 2 C_2 - C 6 C_6 alkenyl), (cc3) ( C 2 C_2 - C 6 C_6 alkynyl) v -NH( C 2 C_2 - C 6 C_6 alkynyl), ( d d 1 ) ( C 1 − C 6 a l k y l ) w − N ( C 1 − C 6 a l k y l ) 2 , ( d d 2 ) ( C 1 − C 6 a l k y l ) w − N ( C 2 − C 6 a l k e n y l ) 2 , ( d d 3 ) ( C 1 − C 6 a l k y l ) w − N ( C 2 − C 6 a l k e n y l ) 2 (dd1) (C_1-C_6 alkyl)_w-N(C_1-C_6 alkyl)_2, (dd2) (C_1-C_6 alkyl)_w-N(C_2-C_6 alkenyl)_2, (dd3) (C_1-C_6 alkyl)_w-N(C_2-C_6 alkenyl)_2 a l k y l ) w − N ( C 2 − C 6 a l k y n y l ) 2 alkyl)_{w}-N(C_2-C_6 alkynyl)_2 , (ee1) ( C 2 − C 6 a l k e n y l ) w − N ( C 1 − C 6 a l k y l ) 2 (C_2-C_6 alkenyl)_{w}-N(C_1-C_6 alkyl)_2 , (ee2) ( C 2 − C 6 a l k e n y l ) w − N ( C 2 − C 6 a l k e n y l ) 2 (C_2-C_6 alkenyl)_{w}-N(C_2-C_6 alkenyl)_2 C 6 C_6 alkenyl) 2 , (ee3) ( C 2 C_2 - C 6 C_6 alkenyl) w - N ( C 2 N(C_2 - C 6 C_6 alkynyl) 2 , (ff1) ( C 2 C_2 - C 6 C_6 alkynyl) w - N ( C 1 N(C_1 - C 6 C_6 alkyl) 2 , (ff2) (C 2 -C 6 alkynyl) w -N(C 2 -C 6 alkenyl) 2 , (ff3) (C 2 -C 6 alkynyl) w -N(C 2 -C 6 alkynyl) 2 , (gg) 3-8 membered saturated, unsaturated, or partially saturated carbocycle, or (hh) 3-8 membered saturated, unsaturated, or partially saturated heterocycle, wherein each of (i)-(hh) is optionally substituted with one or more R 7 R^7 ; [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] represents an aromatic, saturated, unsaturated, or partially saturated carbocycle comprising one or two 3-8 membered rings, or an aromatic, saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-8 membered rings and one or more heteroatoms selected from N, O and S, wherein the two 3-8 membered rings or the two 5-8 membered rings can form a fused or bridged ring structure; [Image disponible dans le document PDF, Image available in the PDF document] each R 5 is at the 2 or 3 position of , and is independently (a) halogen, (b) OH, (c) CONH 2 , (d) COOH, (e) CN, (f) N 3 , (g) C 1 -C 6 alkyl, (h) C 2 -C 6 alkenyl, (i) C 2 -C 6 alkynyl, (j) O- ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl}) , ( k ) (k) O- ( C 2 − C 6 alkenyl ) (C_2-C_6 \text{ alkenyl}) , ( l ) (l) O- ( C 2 − C 6 alkynyl ) (C_2-C_6 \text{ alkynyl}) , ( m ) (m) COO- ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl}) , ( n ) (n) COO- ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl}) , ( n ) (n) COO- ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl}) , ( n ) (n) COO- ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl}) , C 2 C_2 - C 6 C_6 alkenyl), (o) COO-( C 2 C_2 - C 6 C_6 alkynyl), (p) CONH-( C 1 C_1 - C 6 C_6 alkyl), (q) CONH-( C 2 C_2 - C 6 C_6 alkenyl), (r) CONH-( C 2 C_2 - C 6 C_6 alkynyl), (s) CON( C 1 C_1 - C 6 C_6 alkyl) 2 , (t) CON( C 2 C_2 - C 6 C_6 alkenyl) 2 , (u) CON( C 2 C_2 - C 6 C_6 alkynyl) 2 , (v1) ( C 1 − C 6 alkyl ) v (C_1-C_6 \text{ alkyl})_v -NH ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl}) , (v2) ( C 1 − C 6 alkyl ) v (C_1-C_6 \text{ alkyl})_v -NH ( C 2 − C 6 alkenyl ) (C_2-C_6 \text{ alkenyl}) , (v3) ( C 1 − C 6 alkyl ) v (C_1-C_6 \text{ alkyl})_v -NH ( C 2 − C 6 alkenyl ) (C_2-C_6 \text{ alkenyl}) , (v3) C 6 C_6 alkyl) v -NH( C 2 C_2 - C 6 C_6 alkynyl), (w1) ( C 2 C_2 - C 6 C_6 alkenyl) v -NH( C 1 C_1 - C 6 C_6 alkyl), (w2) ( C 2 C_2 - C 6 C_6 alkenyl) v - N H ( C 2 − C 6 alkenyl ) , ( w 3 ) ( C 2 − C 6 alkenyl ) v − N H ( C 2 − C 6 alkynyl ) , ( x 1 ) ( C 2 − C 6 alkynyl ) v − N H ( C 1 − C 6 alkenyl ) NH(C_2-C_6 \text{ alkenyl}), (w3) (C_2-C_6 \text{ alkenyl})_v-NH(C_2-C_6 \text{ alkynyl}), (x1) (C_2-C_6 \text{ alkynyl})_v-NH(C_1-C_6 \text{ alkenyl}) alkyl), ( x 2 ) ( C 2 − C 6 alkynyl ) v − N H ( C 2 − C 6 alkenyl ) , ( x 3 ) ( C 2 − C 6 alkynyl ) v − N H ( C 2 − C 6 alkynyl ) , ( y 1 ) (x2) (C_2-C_6 \text{ alkynyl})_v-NH(C_2-C_6 \text{ alkenyl}), (x3) (C_2-C_6 \text{ alkynyl})_v-NH(C_2-C_6 \text{ alkynyl}), (y1) ( C 1 − C 6 alkyl ) w − N ( C 1 − C 6 alkyl ) 2 (C_1-C_6 \text{ alkyl})_w-N(C_1-C_6 \text{ alkyl})_2 , ( y 2 ) ( C 1 − C 6 alkyl ) w − N ( C 2 − C 6 alkenyl ) 2 (y2)(C_1-C_6 \text{ alkyl})_w-N(C_2-C_6 \text{ alkenyl})_2 , ( y 3 ) ( C 1 − C 6 alkyl ) w − N ( C 2 − C 6 alkyl ) w (y3)(C_1-C_6 \text{ alkyl})_w-N(C_2-C_6 \text{ alkyl})_w C 6 C_6 alkynyl) 2 , (z1) ( C 2 C_2 - C 6 C_6 alkenyl) w - N ( C 1 N(C_1 - C 6 C_6 alkyl) 2 , (z2) ( C 2 C_2 - C 6 C_6 alkenyl) w - N ( C 2 N(C_2 - C 6 C_6 alkenyl) 2 , ( z 3 ) ( C 2 − C 6 alkenyl ) w − N ( C 2 − C 6 alkynyl ) 2 (z3) (C_2-C_6 \text{ alkenyl})_w-N(C_2-C_6 \text{ alkynyl})_2 , ( a a 1 ) ( C 2 − C 6 alkynyl ) w − N ( C 1 − C 6 alkyl ) 2 (aa1) (C_2-C_6 \text{ alkynyl})_w-N(C_1-C_6 \text{ alkyl})_2 , ( a a 2 ) ( C 2 − C 6 alkynyl ) w (aa2) (C_2-C_6 \text{ alkynyl})_w alkynyl) w -N( C 2 C_2 - C 6 C_6 alkenyl) 2 , (aa3) ( C 2 C_2 - C 6 C_6 alkynyl) w -N( C 2 C_2 - C 6 C_6 alkynyl) 2 , (bb) S-( C 1 C_1 - C 6 C_6 alkyl), (cc) S ( O ) S(O) -( C 1 C_1 - C 6 C_6 alkyl), (dd) S ( O ) 2 S(O)_2 -( C 1 C_1 - C 6 C_6 alkyl), (ee) S S -( C 2 C_2 - C 6 C_6 alkenyl), (ff) S ( O ) S(O) -( C 2 C_2 - C 6 C_6 alkenyl), (gg) S ( O ) 2 S(O)_2 -( C 2 C_2 - C 6 C_6 alkenyl), (hh) S S -( C 2 C_2 - C 6 C_6 alkynyl), (ii) S ( O ) S(O) -( C 2 C_2 - C 6 C_6 alkynyl), (jj) S(O) 2 -(C 2 -C 6 alkynyl), (kk) an aromatic, saturated, unsaturated, or partially saturated carbocycle comprising one or two 3-8 membered rings, or (11) an aromatic, saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-7 membered rings and one or more heteroatoms selected from N, O and S, wherein each of (g)-(ll) is optionally substituted with one or more R 8 ; each R 6 is independently (a) halogen, (b) OH, (c) CONH 2 , (d) COOH, (e) CN, (f) N 3 , (g) C 1 C_1 - C 6 C_6 alkyl, (h) C 2 C_2 - C 6 C_6 alkenyl, (i) C 2 C_2 - C 6 C_6 alkynyl, (j) O O -( C 1 C_1 - C 6 C_6 alkyl), (k) O O -( C 2 C_2 - C 6 C_6 alkenyl), (l) O − ( C 2 − C 6 alkynyl ) O-(C_2-C_6 \text{ alkynyl}) , (m) C O O − ( C 1 − C 6 alkyl ) COO-(C_1-C_6 \text{ alkyl}) , (n) C O O − ( C 2 − C 6 alkenyl ) COO-(C_2-C_6 \text{ alkenyl}) , (o) C O O − ( C 2 − C 6 alkenyl ) COO-(C_2-C_6 \text{ alkenyl}) alkynyl), (p) CONH-(C 1 -C 6 alkyl), (q) CONH-(C 2 -C 6 alkenyl), (r) CONH-(C 2 -C 6 alkynyl), (s) C O N ( C 1 − C 6 alkyl ) 2 CON(C_1-C_6 \text{ alkyl})_2 , (t) C O N ( C 2 − C 6 alkenyl ) 2 CON(C_2-C_6 \text{ alkenyl})_2 , (u) C O N ( C 2 − C 6 alkynyl ) 2 CON(C_2-C_6 \text{ alkynyl})_2 , (v1) ( C 1 − C 6 alkyl ) v (C_1-C_6 \text{ alkyl})_v - N H ( C 1 − C 6 alkyl ) , ( v 2 ) ( C 1 − C 6 alkyl ) v − N H ( C 2 − C 6 alkenyl ) , ( v 3 ) ( C 1 − C 6 alkyl ) v − N H ( C 2 − C 6 alkynyl ) , NH(C_1-C_6 \text{ alkyl}), (v2) (C_1-C_6 \text{ alkyl})_v-NH(C_2-C_6 \text{ alkenyl}), (v3) (C_1-C_6 \text{ alkyl})_v-NH(C_2-C_6 \text{ alkynyl}), ( w 1 ) ( C 2 − C 6 alkenyl ) v − N H ( C 1 − C 6 alkyl ) , ( w 2 ) ( C 2 − C 6 alkenyl ) v − N H ( C 2 − C 6 alkenyl ) , ( w 3 ) ( C 2 − C 6 alkenyl ) v (w1) (C_2-C_6 \text{ alkenyl})_v-NH(C_1-C_6 \text{ alkyl}), (w2) (C_2-C_6 \text{ alkenyl})_v-NH(C_2-C_6 \text{ alkenyl}), (w3) (C_2-C_6 \text{ alkenyl})_v alkenyl) v _{v} -NH(C 2 -C 6 alkynyl), (x1) (C 2 -C 6 alkynyl) v _{v} -NH(C 1 -C 6 alkyl), (x2) (C 2 -C 6 alkynyl) v _{v} - N H ( C 2 − C 6 alkenyl ) , ( x 3 ) ( C 2 − C 6 alkynyl ) v − N H ( C 2 − C 6 alkynyl ) , ( y 1 ) ( C 1 − C 6 alkyl ) w − N ( C 1 − C 6 alkynyl ) NH(C_2-C_6 \text{ alkenyl}), (x3) (C_2-C_6 \text{ alkynyl})_v-NH(C_2-C_6 \text{ alkynyl}), (y1) (C_1-C_6 \text{ alkyl})_w-N(C_1-C_6 \text{ alkynyl}) alkyl) 2 , (y2) (C 1 -C 6 alkyl) w -N(C 2 -C 6 alkenyl) 2 , (y3) (C 1 -C 6 alkyl) w -N(C 2 -C 6 alkynyl) 2 , (z1) (C 2 - C 6 C_6 alkenyl) w -N( C 1 C_1 - C 6 C_6 alkyl) 2 , (z2) ( C 2 C_2 - C 6 C_6 alkenyl) w -N( C 2 C_2 - C 6 C_6 alkenyl) 2 , (z3) ( C 2 C_2 - C 6 C_6 alkenyl) w - N ( C 2 − C 6 alkynyl ) 2 N(C_2-C_6 \text{ alkynyl})_2 , (aa1) ( C 2 − C 6 alkynyl ) w − N ( C 1 − C 6 alkyl ) 2 (C_2-C_6 \text{ alkynyl})_w-N(C_1-C_6 \text{ alkyl})_2 , (aa2) ( C 2 − C 6 alkynyl ) w − N ( C 2 − C 6 alkynyl ) w (C_2-C_6 \text{ alkynyl})_w-N(C_2-C_6 \text{ alkynyl})_w alkenyl) 2 , (aa3) ( C 2 − C 6 alkynyl ) w (C_2-C_6 \text{ alkynyl})_w -N ( C 2 − C 6 alkynyl ) 2 (C_2-C_6 \text{ alkynyl})_2 , (bb) S- ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl}) , (cc) S(O)- ( C 1 − C 6 alkynyl ) w (C_1-C_6 \text{ alkynyl})_w -N(C 2 -C 6 alkynyl) 2 , (bb) S- ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl}) , (cc) S(O)-<Formule mathématique disponible dans le document PDF, Math available in the PDF document>(C_1-C_6 \text{ alky alkyl), (dd) S(O) 2 -(C 1 -C 6 alkyl), (ee) S-(C 2 -C 6 alkenyl), (ff) S(O)-(C 2 -C 6 alkenyl), (gg) S(O) 2 - ( C 2 − C 6 alkenyl ) (C_2-C_6 \text{ alkenyl}) , (hh) S- ( C 2 − C 6 alkynyl ) (C_2-C_6 \text{ alkynyl}) , (ii) S(O)- ( C 2 − C 6 alkynyl ) (C_2-C_6 \text{ alkynyl}) , (jj) S(O) 2 - ( C 2 − C 6 alkynyl ) (C_2-C_6 \text{ alkynyl}) , (kk) an aromatic, saturated, unsaturated, or partially saturated carbocycle comprising one or two 3-8 membered rings, or (ll) an aromatic, saturated, unsaturated, or partially saturated heterocycle comprising one or two 5-7 membered rings and one or more heteroatoms selected from N, O and S, wherein each of (g)-(ll) is optionally substituted with one or more R 9 R^9 ; each R 7 is independently halogen, OH, O-(C 1 -C 6 alkyl), COO-(C 1 -C 6 alkyl), CONH-(C 1 - C 6 alkyl), CON(C 1 -C 6 alkyl) 2 , COOH, CN, N 3 , 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S; each R 8 is independently halogen, OH, O-(C 1 -C 6 alkyl), C 1 -C 6 haloalkyl, COO-(C 1 -C 6 alkyl), CONH-(C 1 -C 6 alkyl), CON(C 1 -C 6 alkyl) 2 , COOH, CN, N 3 , 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S; each R 9 is independently halogen, OH, O-(C 1 -C 6 alkyl), COO-(C 1 -C 6 alkyl), CONH-(C 1 - C 6 alkyl), CON(C 1 -C 6 alkyl) 2 , COOH, CN, N 3 , 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle comprising one or more heteroatoms selected from N, O and S; R 101 R^{101} and R 102 R^{102} are each independently H, C 1 C_1 - C 6 C_6 alkyl, C 2 C_2 - C 6 C_6 alkenyl, or C 2 C_2 - C 6 C_6 alkynyl; R 11 R^{11} is H, halogen, C 1 C_1 - C 6 C_6 alkyl, C 2 C_2 - C 6 C_6 alkenyl, or C 2 C_2 - C 6 C_6 alkynyl; R 12 R^{12} is H, halogen, C 1 C_1 - C 6 C_6 alkyl, C 2 C_2 - C 6 C_6 alkenyl, or C 2 C_2 - C 6 C_6 alkynyl; m is 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; t is 0, 1, or 2; u is 0 or 1; v is 0 or 1; and w is 0 or 1.

2. The compound of claim 1, wherein X a X_a is N; and X b X_b is C R b CR^b .

3. The compound of claim 1 or 2, wherein R 11 R^{11} is H; and R 12 R^{12} is H.

4. The compound of any one of claim 1 or 2, wherein R 11 R^{11} is C 1 C_1 - C 6 C_6 alkyl; and R 12 R^{12} is H.

5. The compound of any one of claims 1 to 4, wherein X c X_c is C R c CR^c ; and X d X_d is C R d CR^d .

6. The compound of any one of claims 1 to 5, wherein R 3 is H; and R 4 is H.

7. The compound of any one of claims 1 to 6, wherein R a R^a is H, halogen, or C 1 C_1 - C 6 C_6 alkyl.

8. The compound of any one of claims 1 to 7, wherein R b R^b is H, halogen, or C 1 C_1 - C 6 C_6 alkyl.

9. The compound of any one of claims 1 to 8, wherein R c R^c is H, halogen, or C 1 C_1 - C 6 C_6 alkyl.

10. The compound of any one of claims 1 to 9, wherein R d R^d is H, halogen, or C 1 C_1 - C 6 C_6 alkyl.

11. The compound of claim 1, wherein R 3 is H, halogen, OH, COOH, CONH 2 , NHCOR 101 , NR 101 COR 102 , S(O) t R 101 , C 1 -C 6 alkyl, O-(C 1 -C 6 alkyl), COO-(C 1 -C 6 alkyl), CONH-(C 1 -C 6 alkyl), C O N ( C 1 − C 6 alkyl ) 2 CON(C_1-C_6 \text{ alkyl})_2 , ( C 1 − C 6 alkyl ) u − N H 2 (C_1-C_6 \text{ alkyl})_u-NH_2 , ( C 1 − C 6 alkyl ) v − N H ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl})_v-NH(C_1-C_6 \text{ alkyl}) , ( C 1 − C 6 alkyl ) w − N ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl})_w-N(C_1-C_6 \text{ alkyl}) alkyl)2, or 5-6 membered saturated, unsaturated, or partially saturated carbocycle, each of which is optionally substituted with one or more ℝ 7 \mathbb{R}^7 .

12. The compound of claim 1, wherein R 4 is H, halogen, OH, COOH, CONH 2 , NHCOR 101 , NR 101 COR 102 , S(O) t R 101 , C 1 -C 6 alkyl, O-(C 1 -C 6 alkyl), COO-(C 1 -C 6 alkyl), CONH-(C 1 -C 6 alkyl), C O N ( C 1 − C 6 alkyl ) 2 CON(C_1-C_6 \text{ alkyl})_2 , ( C 1 − C 6 alkyl ) u − N H 2 (C_1-C_6 \text{ alkyl})_u-NH_2 , ( C 1 − C 6 alkyl ) v − N H ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl})_v-NH(C_1-C_6 \text{ alkyl}) , ( C 1 − C 6 alkyl ) w − N ( C 1 − C 6 alkyl ) (C_1-C_6 \text{ alkyl})_w-N(C_1-C_6 \text{ alkyl}) alkyl)2, or 5-6 membered saturated, unsaturated, or partially saturated carbocycle, each of which is optionally substituted with one or more ℝ 7 \mathbb{R}^7 .

13. The compound of claim 1, wherein R 4 is H; and R 3 is halogen, OH, COOH, CONH 2 , NHCOR 101 , NR 101 COR 102 , S(O) t R 101 , C 1 -C 6 alkyl, O-(C 1 -C 6 alkyl), COO-(C 1 -C 6 alkyl), CONH- ( C 1 − C 6 alkyl ) , C O N ( C 1 − C 6 alkyl ) 2 , ( C 1 − C 6 alkyl ) u − N H 2 , ( C 1 − C 6 alkyl ) v − N H ( C 1 − C 6 alkyl ) , ( C 1 − C 6 alkyl ) v − N H ( C 1 − C 6 alkyl ) v − N H ( C 1 − C 6 alkyl ) v − N H ( C 1 − C 6 alkyl ) v − N H ( C 1 (C_1-C_6 \text{ alkyl}), CON(C_1-C_6 \text{ alkyl})_2, (C_1-C_6 \text{ alkyl})_u-NH_2, (C_1-C_6 \text{ alkyl})_v-NH(C_1-C_6 \text{ alkyl}), (C_1-C_6 \text{ alkyl})_v-NH(C_1-C_6 \text{ alkyl})_v-NH(C_1-C_6 \text{ alkyl})_v-NH(C_1-C_6 \text{ alkyl})_v-NH(C_1 alkyl) w -N(C 1 -C 6 alkyl) 2 , or 5-6 membered saturated, unsaturated, or partially saturated carbocycle.

14. The compound of claim 1, wherein R 3 R^3 is halogen, C 1 C_1 - C 6 C_6 alkyl, or O-( C 1 C_1 - C 6 C_6 alkyl).

15. The compound of claim 1, wherein R 1 R^1 is H; and R 2 R^2 is H.

16. The compound of claim 1, wherein one of R 1 R^1 and R 2 R^2 , together with the carbon atom to which R 1 R^1 or R 2 R^2 is attached and ( B ) \binom{B}{} , form a 7-12 membered saturated, unsaturated, or partially saturated carbocycle, or a 7-12 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S.

17. The compound of claim 1, wherein m is 1.

18. The compound of claim 1, wherein R 5 is (a) halogen, (b) OH, (c) CONH 2 , (d) COOH, (e) CN, (f) N 3 , (g) C 1 -C 6 alkyl, (h) C 2 -C 6 alkenyl, (j) O-(C 1 -C 6 alkyl), (m) COO-(C 1 -C 6 alkyl), (p) CONH-(C 1 -C 6 alkyl), or (s) CON(C 1 -C 6 alkyl) 2 , each of which is optionally substituted with one or more R 8 .

19. The compound of claim 1, wherein R 5 is halogen, C 1 -C 6 alkyl, or O-C 1 -C 6 alkyl.

20. The compound of any one of claims 1 to 19, wherein R 5 R^5 is C 1 C_1 - C 6 C_6 alkyl.

21. The compound of claim 1, wherein R 5 is in the S-configuration. [Image disponible dans le document PDF, Image available in the PDF document]22. The compound of claim 1, wherein represents a 6 membered aromatic carbocycle. [Image disponible dans le document PDF, Image available in the PDF document]23. The compound of claim 1, wherein represents an aromatic heterocycle comprising one or more heteroatoms selected from N, O and S. [Image disponible dans le document PDF, Image available in the PDF document]24. The compound of claim 1, wherein represents pyridine.

25. The compound of claim 1, wherein n is 0.

26. The compound of claim 1, wherein n is 1.

27. The compound of claim 1, wherein R 6 is (a) halogen, (b) OH, (c) CONH 2 , (d) COOH, (e) CN, (f) N 3 , (g) C 1 -C 6 alkyl, (h) C 2 -C 6 alkenyl, (j) O-(C 1 -C 6 alkyl), (m) COO-(C 1 -C 6 alkyl), (p) CONH-(C 1 -C 6 alkyl), or (s) CON(C 1 -C 6 alkyl) 2 , each of which is optionally substituted with one or more R 9 R^9 .

28. The compound of claim 1, wherein R 6 R^6 is halogen, C 1 C_1 - C 6 C_6 alkyl, or O- C 1 C_1 - C 6 C_6 alkyl.

29. The compound of claim 1, wherein R 6 R^6 is at the 2- or 4-position.

30. A compound of formula (I): [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt or solvate thereof, wherein: X a is CR a or N; X b is CR b or N; X c is CR c or N; X d is CR d or N; R a R^a is H, halogen, or C 1 C_1 - C 6 C_6 alkyl; R b is H, halogen, or C 1 -C 6 alkyl; R c R^c is H, halogen, or C 1 C_1 - C 6 C_6 alkyl; R d R^d is H, halogen, or C 1 C_1 - C 6 C_6 alkyl; R 1 R^1 and R 2 R^2 are each independently H, C 1 C_1 - C 6 C_6 alkyl, or O-( C 1 C_1 - C 6 C_6 alkyl); alternatively, one of R 1 and R 2 , together with the carbon atom to which R 1 or R 2 is attached and (B), form a 7-12 membered saturated, unsaturated, or partially saturated carbocycle, or a 7-12 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S; R 3 and R 4 are each independently (a) H, (b) halogen, (c) OH, (d) COOH, (e) CONH 2 , (f) NHCOR 101 , (g) NR 101 COR 102 , (h) S(O) t R 101 , (i) C 1 -C 6 alkyl, (j) O-(C 1 -C 6 alkyl), (k) COO-(C 1 -C 6 alkyl), (1) CONH-( C 1 C_1 - C 6 C_6 alkyl), (m) CON( C 1 C_1 - C 6 C_6 alkyl) 2 , (n) ( C 1 C_1 - C 6 C_6 alkyl) u -NH 2 , (o) ( C 1 C_1 - C 6 C_6 alkyl) v -NH( C 1 C_1 - C 6 C_6 alkyl), (p) ( C 1 C_1 - C 6 C_6 alkyl) w -N( C 1 C_1 - C 6 C_6 alkyl) 2 , or (q) 5-6 membered saturated, unsaturated, or partially saturated carbocycle, wherein each of (i)-(q) is optionally substituted with one or more R'; [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] represents a 5-6 membered aromatic, saturated, unsaturated, or partially saturated carbocycle, or a 5-6 membered aromatic, saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S; [Image disponible dans le document PDF, Image available in the PDF document] each R 5 is at the 2 or 3 position of , and is independently (a) halogen, (b) OH, (c) C 1 -C 6 alkyl, (d) C 2 -C 6 alkenyl, (e) O-(C 1 -C 6 alkyl), (f) COO-(C 1 -C 6 alkyl), (g) CONH-(C 1 -C 6 alkyl), (h) CON(C 1 -C 6 alkyl) 2 , (i) COOH, (j) CN, or (k) N 3 , wherein each of (c)-(h) is optionally substituted with one or more R 8 ; each R 6 is independently (a) halogen, (b) OH, (c) C 1 -C 6 alkyl, (d) C 2 -C 6 alkenyl, (e) O- ( C 1 − C 6 alkyl ) , ( f ) COO- ( C 1 − C 6 alkyl ) , ( g ) CONH- ( C 1 − C 6 alkyl ) , ( h ) CON ( C 1 − C 6 alkyl ) 2 , ( i ) (C_1-C_6 \text{ alkyl}), (f) \text{ COO-}(C_1-C_6 \text{ alkyl}), (g) \text{ CONH-}(C_1-C_6 \text{ alkyl}), (h) \text{ CON}(C_1-C_6 \text{ alkyl})_2, (i) COOH, (j) CN, or (k) N 3 , wherein each of (c)-(h) is optionally substituted with one or more R 9 ; each R 7 is independently halogen, OH, O-(C 1 -C 6 alkyl), COO-(C 1 -C 6 alkyl), CONH-(C 1 - C 6 alkyl), CON(C 1 -C 6 alkyl) 2 , COOH, CN, N 3 , 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S; each R 8 is independently halogen, OH, O-(C 1 -C 6 alkyl), C 1 -C 6 haloalkyl, COO-(C 1 -C 6 alkyl), CONH-(C 1 -C 6 alkyl), CON(C 1 -C 6 alkyl) 2 , COOH, CN, N 3 , 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S; each R 9 is independently halogen, OH, O-(C 1 -C 6 alkyl), COO-(C 1 -C 6 alkyl), CONH-(C 1 - C 6 alkyl), CON(C 1 -C 6 alkyl) 2 , COOH, CN, N 3 , 5-6 membered saturated, unsaturated, or partially saturated carbocycle, or 5-6 membered saturated, unsaturated, or partially saturated heterocycle containing one or more heteroatoms selected from N, O and S; R 101 R^{101} and R 102 R^{102} are each independently H or C 1 C_1 - C 6 C_6 alkyl; R 11 R^{11} is H, halogen, or C 1 C_1 - C 6 C_6 alkyl; R 12 R^{12} is H, halogen, or C 1 C_1 - C 6 C_6 alkyl; m is 1, 2, 3, 4, 5, or 6; n is 0, 1, 2, 3, 4, 5, or 6; t is 0, 1, or 2; u is 0 or 1; v is 0 or 1; and w is 0 or 1.

31. The compound of any one of claims 1 to 30, wherein the compound is of formula (II): [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt or solvate thereof.

32. The compound of claim 30, wherein the compound is of formula (III): [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt or solvate thereof, wherein n1 is 0, 1, 2, 3, 4, or 5.

33. The compound of claim 30, wherein the compound is of the following formula: [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt or solvate thereof.

34. The compound of claim 30, wherein the compound is of the following formula: [Image disponible dans le document PDF, Image available in the PDF document] , or a pharmaceutically acceptable salt or solvate thereof.

35. The compound of claim 30, wherein the compound is of the following formula: [Image disponible dans le document PDF, Image available in the PDF document] [Image disponible dans le document PDF, Image available in the PDF document] or a pharmaceutically acceptable salt or solvate thereof.

36. The compound of claim 30, wherein the compound is of the following formula: [Image disponible dans le document PDF, Image available in the PDF document] , or a pharmaceutically acceptable salt or solvate thereof, wherein: / - n2 is 0, 1, 2, or 3; n3 is 0, 1, or 2; and A 1 , A 2 , and A 3 are each independently CR 61 or N, and wherein only one of A 1 , A 2 , and A 3 is N; and R 61 R^{61} is H or R 6 R^6 .

37. The compound of claim 30, wherein R 5 is halogen, C 1 -C 6 alkyl, or O-C 1 -C 6 alkyl.

38. The compound of claim 30, wherein R 5 R^5 is C 1 C_1 - C 6 C_6 alkyl.

39. The compound of claim 30wherein R 5 is methyl.

40. The compound of claim 36, wherein n2 is 1.

41. The compound of claim 30, wherein R 6 R^6 is halogen, C 1 C_1 - C 6 C_6 alkyl, O O - C 1 C_1 - C 6 C_6 alkyl, or C N CN .

42. The compound of claim 30, wherein R 6 R^6 is halogen.

43. The compound of claim 30, wherein R 6 R^6 is fluoro.

44. The compound of claim 30, wherein R 6 R^6 is at the 2- or 4-position.

45. The compound of claim 30, wherein R 3 R^3 is halogen, C 1 C_1 - C 6 C_6 alkyl, or O-( C 1 C_1 - C 6 C_6 alkyl).

46. The compound of claim 30, wherein R 3 R^3 is C 1 C_1 - C 6 C_6 alkyl.

47. The compound of claim 30, wherein ℝ 3 \mathbb{R}^3 is methyl.

48. The compound of claim 30, wherein R 1 R^1 is H; and R 2 R^2 is H.

49. A pharmaceutical composition comprising the compound of any one of claims 1 to 48, or a pharmaceutically acceptable salt or solvate thereof, and a pharmaceutically acceptable carrier.

50. Use of the compound of any one of claims 1 to 48, or a pharmaceutically acceptable salt or solvate thereof, or the pharmaceutical composition of claim 49 for preventing or treating a disease or disorder in a subject in need thereof.

51. Use of the compound of any one of claims 1 to 48, or a pharmaceutically acceptable salt or solvate thereof, or the pharmaceutical composition of claim 49 in the manufacture of a medicament for preventing or treating a disease or disorder in a subject in need thereof.

52. A compound of any one of claims 1 to 48, or a pharmaceutically acceptable salt or solvate thereof, or the pharmaceutical composition of claim 49 for use in preventing or treating a disease or disorder in a subject in need thereof.