GPCR receptor agonists, pharmaceutical compositions containing same, and methods of use thereof

Abstract

Provided herein are GLP-1 receptor modulator compounds, pharmaceutical compositions, methods for their preparation, and methods for their use in treatment and / or diagnosis. Provided herein are GLP-1 receptor modulator compounds of formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and subformulas thereof, compositions comprising the compounds, methods for making the compounds, and methods for the therapeutic and diagnostic use of the compounds and crude products.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is a PCT international application claiming the benefit of U.S. Provisional Application No. 63 / 274,893, filed November 2, 2021, U.S. Provisional Application No. 63 / 183,612, filed May 3, 2021, and U.S. Provisional Application No. 63 / 143,025, filed January 28, 2021, the entire contents of each of which are incorporated herein by reference.

[0002] Provided herein are GLP-1 receptor modulator compounds, pharmaceutical compositions containing the compounds, methods for making the compounds, and methods of using the compounds and compositions for therapy. The compounds and compositions are useful, for example, in methods for treating and preventing metabolic diseases or conditions, detecting metabolic diseases or conditions, and diagnosing metabolic diseases or conditions. [Background technology]

[0003] Diabetes is a serious chronic disease that occurs when the pancreas does not produce enough insulin or when the body is unable to effectively use the insulin it produces. Diabetes complications include damage to the heart, blood vessels, eyes, kidneys, and nerves. Diabetes can increase the risk of heart disease and stroke. The consequences include serious impacts on quality of life, health, and mortality. WHO Global Report on Diabetes, 2016, World Health Organization. As of 2017, approximately 462 million people worldwide, or approximately 6.28% of the population, had type 2 diabetes, and this prevalence is increasing significantly. Khan et al., 2020, J. Epidemiol. Glob. Health 10(1):107-111. The global economic burden of diabetes was estimated at $1.3 trillion in 2015 and is estimated to increase to $2.1 trillion by 2030. Bommer et al., 2018, Diabetes Care 41(5):963-970. Approximately 90-95% of all diabetes cases are type 2 diabetes. Tripathi & Srivastava, 2016, Med. Sci. Monit. 12(7):RA130-147.

[0004] The glucagon-like peptide-1 receptor (GLP-1 receptor, or GLP1R) has emerged as a potential target for treating type 2 diabetes. Its ligand, glucagon-like peptide-1 (GLP-1), promotes glucose-induced insulin secretion and increases insulin synthesis, among many other effects. (Doyle and Egan, 2007, Pharmacol. Ther. 113(3):546-593) GLP-1 is known to delay gastric emptying, suppress food intake, increase satiety, and reduce body weight in humans. (Shah and Vella, 2014 Rev Endocr Metab Disord. 15(3):181-187) Activation of the GLP-1 receptor has been shown to have beneficial effects on insulin secretion and on maintaining beta-cell glucose sensing, transcription, synthesis, proliferation, and survival. (Doyle and Egan, 2007, supra) Although the GLP-1 receptor is a promising therapeutic target, only a handful of GLP-1 receptor drugs have been approved to date, and most or all of these are peptide or polypeptide drugs. Additional therapies are needed to treat metabolic diseases and conditions, such as type 2 diabetes. Small molecules that target the GLP-1 receptor should provide safe, stable, and easily administered therapeutic agents for metabolic diseases and conditions, such as type 2 diabetes. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Khan et al.,2020,J.Epidemiol.Glob.Health 10(1):107-111 [Non-patent document 2] Bommer et al.,2018,Diabetes Care 41(5):963-970 [Non-patent document 3] Tripathi & Srivastava,2016,Med.Sci.Monit.12(7):RA130-147 [Non-patent document 4] Doyle and Egan,2007,Pharmacol.Ther.113(3):546-593 [Non-Patent Document 5] Shah and Vella,2014 Rev Endocr Metab Disord.15(3):181-187 Summary of the Invention [Means for solving the problem]

[0006] Provided herein are GLP-1 receptor modulator compounds of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), and subformulas thereof, compositions comprising the compounds, methods of producing the compounds, and methods of using the compounds and crude products in therapy and diagnosis. Compounds of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), and embodiments thereof, are useful for modulating the activity of the GLP-1 receptor. In certain embodiments, the compounds can be used to agonize the activity of the GLP-1 receptor. In certain embodiments, the compounds can be used to treat diseases or conditions modulated by the GLP-1 receptor.

[0007] In one aspect, there is provided a compound of formula (I), or a pharmaceutically acceptable salt, or stereoisomer thereof: [ka] wherein A is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, -NMe2, or -CF3; Ring B is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, or a substituted or unsubstituted bicyclic; Ring C is a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heterocycloalkenyl, each of which is L as shown.3 containing at least one N bonded to D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and; W, N, CR 14 , or C; W is CR 14 When W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=; L 1 is selected from the group consisting of a bond, —O—, —CH—, —NH—, —N(Me)—, —N(Et)—, —OCH—, —OC(H,Me)—, —CHO—, —NHCH—, —N(Me)CH—, and —SONH—; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; L 4 does not exist or L 4 L 1 and together with rings A and B form a fused tricyclic ring, and L 5 does not exist; L 5 does not exist or L 5 L 2 and together with rings B and C form a fused tricyclic ring, and L 4 does not exist; R 4is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; Each R 6 are independently alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO- and R 11 R 12 N-; R 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; R 13 is hydrogen or alkyl; R 14 is hydrogen, cyano, halo, hydroxyl, alkyl, haloalkyl, methyl, CHF, or CHOH; In the formula, L 1 is -CH2O-, and L 4 does not exist and L 5 If does not exist, then L 2 is -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, or [ka] or L 3 is -C(O)-, or both.

[0008] In one aspect, there is provided a compound of formula (Ia), or a pharmaceutically acceptable salt, or stereoisomer thereof: [ka] wherein A is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, -NMe2, or -CF3; Ring B is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Ring C is further unsubstituted or further substituted and / or bridged; D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and; W is N, CH, or C; when W is CH, the adjacent dashed line represents a single bond; When W is C, one adjacent dashed line indicates a double bond, e.g., L 2 is -C(H)=; L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; L 4 does not exist or L 4 L 1 and together with rings A and B form a fused tricyclic ring, and L 5 does not exist; L5 does not exist or L 5 L 2 and together with rings B and C form a fused tricyclic ring, and L 4 does not exist; R 4 is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; Each R 6 is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO- and R 11 R 12 N-, independently selected from the group consisting of: R 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; and R 13 is hydrogen or alkyl; In the formula, L 1 is -CH2O-, and L 4 does not exist and L 5 If does not exist, then L 2 is -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, or [ka] or L 3is -C(O)-, or both.

[0009] In one aspect, there is provided a compound of formula (XXX), or a pharmaceutically acceptable salt, or stereoisomer thereof: [ka] In the formula, W is N, CH, or C; when W is CH, the adjacent dashed line represents a single bond; when W is C, the adjacent dashed line represents a double bond, e.g., L 2 is -C(H)=; A 1 , A 2 , A 3 , A 4 , and A 5 0, 1, or 2 of these are N, and the rest are CH or CR 1 and; B 1 , B 2 , B 3 , and B 4 0, 1, or 2 of these are N, and the rest are CH or CR 2 and; D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and; L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; Each R1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 independently selected from the group consisting of NCO-; Each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 independently selected from the group consisting of NCO-; Each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 independently selected from the group consisting of NCO-; R 4 is unsubstituted alkyl, substituted alkyl, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; Each R 6 is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO- and R 11 R 12 N-, independently selected from the group consisting of: R 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; R 13 is hydrogen or alkyl; and o is an integer of 0 to 4.

[0010] In one aspect, provided herein is a compound of Formula XXXI, or a pharmaceutically acceptable salt, or stereoisomer thereof: [ka] In the formula, W is N, CH, or C; when W is CH, the adjacent dashed line indicates a single atom; A 1 , A 2 , A 3 , A 4 , and A 5 0, 1, or 2 of these are N, and the rest are CH or CR 1 and; D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and; Each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 independently selected from the group consisting of NCO-; L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; Each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 independently selected from the group consisting of NCO-; R 4is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; Each R 6 is independently selected from the group consisting of F and methyl; R 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; R 13 is hydrogen or alkyl; and o is 1, 2, 3, or 4.

[0011] In certain aspects, the compounds are useful in methods for treating and preventing metabolic diseases and conditions, detecting metabolic diseases and conditions, and diagnosing metabolic diseases and conditions.

[0012] In another aspect, provided are compositions comprising a compound of Formula (I), (Ia), (XXX), or (XXXI). In some embodiments, the composition is a pharmaceutical composition. Any suitable pharmaceutical composition may be used. In a further aspect, provided herein are kits comprising a compound of Formula (I), (Ia), (XXX), or (XXXI), or an embodiment thereof, or a pharmaceutical composition thereof.

[0013] In another aspect, provided herein are methods of using the compounds or compositions described herein. In some embodiments, the methods are for treatment. In some embodiments, the methods are diagnostic methods. In some embodiments, the methods are analytical methods. In some embodiments, the compounds or compositions described herein are used to treat a disease or condition. In some aspects, the disease or condition is selected from metabolic diseases or conditions. In certain embodiments, the disease is type 2 diabetes.

[0014] Also provided herein are uses of the compounds described herein and compositions thereof for the treatment of metabolic diseases or conditions. Also provided herein are uses of the compounds described herein and compositions thereof for the treatment of type 2 diabetes. [Brief explanation of the drawings]

[0015] [Figure 1] 1 shows an intravenous glucose tolerance test (IVGTT) in cynomolgus monkeys. DETAILED DESCRIPTION OF THE INVENTION

[0016] Described herein are GLP-1 receptor compounds that are useful in the treatment of metabolic diseases or conditions, such as type 2 diabetes.

[0017] definition Unless otherwise defined, all technical terms, notations, and other scientific terminology used herein shall have the meanings that are commonly understood by those of ordinary skill in the art to which this disclosure pertains. In some cases, terms with commonly understood meanings are defined herein for the sake of clarity and / or ready reference. The techniques and procedures described or referred to herein are generally well understood and commonly employed by those of ordinary skill in the art using conventional methodology. Where appropriate, procedures involving the use of commercially available kits and reagents are generally performed in accordance with manufacturer-defined protocols and conditions unless otherwise noted.

[0018] As used herein, the singular forms "a", "an" and "the" include plural referents unless the context clearly indicates otherwise.

[0019] The term "about" denotes and encompasses the indicated value, as well as a range above and below that value. In certain embodiments, the term "about" denotes ±10%, ±5%, or ±1% of the specified value. In certain embodiments, the term "about" denotes the specified value ±1 standard deviation of that value. In certain embodiments, for example, on a logarithmic scale (e.g., pH), the term "about" denotes ±0.3, ±0.2, or ±0.1 of the specified value.

[0020] When referring to the compounds provided herein, the following terms have the following meanings unless otherwise specified. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. In the event that there are multiple definitions for terms herein, those in this section prevail unless stated otherwise.

[0021] "Alkoxy" and "alkoxyl" refer to the group -OR" where R" is alkyl or cycloalkyl. Alkoxy groups, in certain embodiments, include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, and the like.

[0022] As used herein, the term "alkoxyamine" refers to an -alkylene-O-NH group, where alkylene is as defined herein. In some embodiments, an alkoxyamine group can react with an aldehyde to form an oxime residue. Examples of alkoxyamine groups include -CHCH-O-NH and -CH-O-NH.

[0023] The term "alkyl," as used herein, unless otherwise specified, refers to a saturated, straight-chain or branched hydrocarbon. In certain embodiments, an alkyl group is a primary, secondary, or tertiary hydrocarbon. In certain embodiments, an alkyl group contains 1 to 10 carbon atoms (i.e., C1 to C6). 10 In certain embodiments, alkyl is a lower alkyl, e.g., C 1-6 and alkyl. In certain embodiments, the alkyl group is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secbutyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, isohexyl, 3-methylpentyl, 2,2-dimethylbutyl, and 2,3-dimethylbutyl. In certain embodiments, "substituted alkyl" refers to an alkyl substituted with one, two, or three groups independently selected from halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, alkoxy, aryl, heteroaryl, cycloalkyl, cyano, oxo, alkyne, and heterocycloalkylalkylene. In some embodiments, the alkyl is unsubstituted.

[0024] The term "alkylene," as used herein, unless otherwise specified, refers to a divalent alkyl group, as defined herein. "Substituted alkylene" refers to an alkylene group substituted as described herein for alkyl. In some embodiments, the alkylene is unsubstituted.

[0025] "Alkenyl" refers, in certain embodiments, to an olefinically unsaturated hydrocarbon group which may be straight-chained or branched, having up to about 11 carbon atoms, or from 2 to 6 carbon atoms (e.g., "lower alkenyl"), and having at least 1, or from 1 to 2 sites of olefinic unsaturation. "Substituted alkenyl" refers to an alkenyl group substituted as described herein for alkyl.

[0026] "Alkenylene" refers to a divalent alkenyl as defined herein. Lower alkenylene is, for example, C2-C6 alkenylene.

[0027] "Alkynyl" refers, in certain embodiments, to an acetylenically unsaturated hydrocarbon group, which may be straight-chained or branched, having up to about 11 carbon atoms, or 2 to 6 carbon atoms (e.g., "lower alkynyl"), and having at least one, or 1 to 2, sites of acetylenic unsaturation. Non-limiting examples of alkynyl groups include acetylene (-C≡CH), propargyl (-CHC≡CH), and the like. "Substituted alkynyl" refers to an alkynyl group substituted as described herein for alkyl.

[0028] "Alkynylene" refers to a divalent alkynyl as defined herein. Lower alkenylene is, for example, C2-C6 alkynylene.

[0029] "Amino" refers to -NH2.

[0030] The term "alkylamino," as used herein, unless otherwise specified, refers to the group -NHR", where R is, for example, C, as defined herein. 1-10 In certain embodiments, alkylamino is C 1-6 It is alkylamino.

[0031] The term "dialkylamino," as used herein, unless otherwise specified, refers to the group -NR"R", where each R" is independently a C, as defined herein. 1-10 In certain embodiments, dialkylamino is di-C 1-6 It is alkylamino.

[0032] The term "aryl," as used herein, refers to phenyl, biphenyl, or naphthyl unless otherwise specified. The term includes both substituted and unsubstituted moieties. Aryl groups can be substituted with any of the listed moieties, including, but not limited to, one or more moieties (e.g., in some embodiments, one, two, or three moieties) selected from the group consisting of halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate, where each moiety is independently unprotected or protected as needed, as understood by one of skill in the art (e.g., Greene et al., Protective Groups in Organic Synthesis, John Wiley and Sons, Second Edition, 1991); and the aryl in the arylamino and aryloxy substituents is not further substituted.

[0033] The term "arylamino", as used herein, unless otherwise specified, refers to the group -NR'R", where R' is hydrogen or C1-C6-alkyl; and R" is aryl as defined herein.

[0034] The term "arylene," as used herein, unless otherwise specified, refers to a divalent aryl group, as defined herein.

[0035] As used herein, unless otherwise specified, the term "aryloxy" means refers to an —OR group, where R is aryl as defined herein.

[0036] "Alkarylene" refers to an arylene group, as defined herein, in which the aryl ring is substituted with one or two alkyl groups. "Substituted alkarylene" refers to an alkarylene, as defined herein, in which the arylene group is further substituted as defined herein for aryl.

[0037] "Aralkylene" refers to an -alkyl-arylene- or arylene-alkyl, e.g., an -C-C alkyl-arylene-, -arylene-C-C alkyl-, or -C-C alkyl-arylene-C-C alkyl- group, where arylene is as defined herein. "Substituted alkarylene" refers to an aralkylene, as defined herein, in which the aralkylene group is substituted as defined herein for aryl. "Substituted C-C alkyl" refers to a C-C alkyl group that is substituted as defined herein for alkyl.

[0038] "Arylalkylene" refers to an -alkyl-arylene- or arylene-alkyl, e.g., an -C1-C2 alkyl-arylene-, -arylene-C1-C2 alkyl-, or -C1-C2 alkyl-arylene-C1-C2 alkyl- group, where arylene is as defined herein. "Substituted arylalkylene" refers to an arylalkylene, as defined herein, in which the arylalkylene group is substituted as defined herein for aryl. "Substituted C1-C2 alkyl" refers to a C1-C2 alkyl group that is substituted as defined herein for alkyl.

[0039] "Carboxyl" or "carboxy" refers to --C(O)OH or --COOH.

[0040] The term "cycloalkyl," as used herein, unless otherwise specified, refers to a saturated cyclic hydrocarbon. In certain embodiments, a cycloalkyl group can be saturated, and / or bridged, and / or unbridged, and / or fused bicyclic groups. In certain embodiments, a cycloalkyl group contains 3 to 10 carbon atoms (i.e., C3 to C6). 10 In some embodiments, cycloalkyl is a cycloalkyl group having 3 to 15 carbons (C 3~15 ), 3 to 10 carbons (C 3~10 ), 3 to 7 carbons (C 3~7 ), or 3 to 6 carbons (C3-C6) (i.e., "lower cycloalkyl"). In certain embodiments, a cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexylmethyl, cycloheptyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, decalinyl, or adamantyl.

[0041] As used herein, the term "cycloalkylene" refers to a divalent cycloalkyl group, as defined herein. In certain embodiments, a cycloalkylene group is [ka] etc. Lower cycloalkylene refers to C3-C6-cycloalkylene.

[0042] The term "cycloalkylalkyl," as used herein, unless otherwise specified, refers to an alkyl group, as defined herein, substituted with one or two cycloalkyl groups, as defined herein.

[0043] As used herein, the term "ester" refers to -C(O)OR, or -COOR, where R is alkyl as defined herein.

[0044] The term "haloalkyl" refers to an alkyl group, as defined herein, substituted with one or more independently selected halogen atoms (e.g., in some embodiments, 1, 2, 3, 4, or 5).

[0045] The term "heteroalkyl" refers to an alkyl, as defined herein, in which one or more carbon atoms are replaced by a heteroatom. As used herein, "heteroalkenyl" refers to an alkenyl, as defined herein, in which one or more carbon atoms are replaced by a heteroatom. As used herein, "heteroalkynyl" refers to an alkynyl, as defined herein, in which one or more carbon atoms are replaced by a heteroatom. Suitable heteroatoms include, but are not limited to, nitrogen (N), oxygen (O), and sulfur (S) atoms. Heteroalkyl, heteroalkenyl, and heteroalkynyl are optionally substituted. Examples of heteroalkyl moieties include, but are not limited to, aminoalkyl, sulfonylalkyl, and sulfinylalkyl. Examples of heteroalkyl moieties also include, but are not limited to, methylamino, methylsulfonyl, and methylsulfinyl. "Substituted heteroalkyl" refers to a heteroalkyl substituted with one, two, or three groups independently selected from halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy. In some embodiments, a heteroalkyl group can contain one, two, three, or four heteroatoms. One of ordinary skill in the art will recognize that a 4-membered heteroalkyl typically contains one or two heteroatoms, a 5- or 6-membered heteroalkyl typically contains one, two, or three heteroatoms, and a 7- to 10-membered heteroalkyl typically can contain one, two, three, or four heteroatoms.

[0046] As used herein, the term "heteroalkylene" refers to a divalent heteroalkyl, as defined herein. "Substituted heteroalkylene" refers to a divalent heteroalkyl, as defined herein, substituted as described for heteroalkyl.

[0047] The term "heterocycloalkyl" refers to a monovalent, monocyclic, or polycyclic non-aromatic ring system where one or more of the ring atoms is a heteroatom independently selected from oxygen (O), sulfur (S), and nitrogen (N) (e.g., the nitrogen or sulfur atom may be optionally oxidized and the nitrogen atom may be optionally quaternized), and the remaining ring atoms of the non-aromatic ring are carbon atoms. In certain embodiments, a heterocycloalkyl is a monovalent, monocyclic, or polycyclic fully saturated ring system. In certain embodiments, a heterocycloalkyl group has 3 to 20, 3 to 15, 3 to 10, 3 to 8, 4 to 7, 4 to 11, or 5 to 6 ring atoms. A heterocycloalkyl can be attached to the core structure at any heteroatom or carbon atom that results in the creation of a stable compound. In certain embodiments, heterocycloalkyl is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, may include fused or bridged ring systems, the nitrogen or sulfur atoms may be optionally oxidized, and / or the nitrogen atoms may be optionally quaternized. In some embodiments, heterocycloalkyl radicals include, but are not limited to, 2,5-diazabicyclo[2.2.2]octanyl, decahydroisoquinolinyl, dihydrobenzisoxazinyl, dihydrofuryl, dihydroisoindolyl, dihydropyranyl, dihydropyrazolyl, dihydropyrazinyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dioxolanyl, 1,4-dithianyl, furanonyl, imidazolidinyl, imidazolinyl, indolinyl, isothiazolyl, In certain embodiments, heterocycloalkyl may also be optionally substituted as described herein.In certain embodiments, heterocycloalkyl is substituted with one, two, or three groups independently selected from halogen (e.g., fluoro (F), chloro (Cl), bromo (Br), or iodo (I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, oxo, cyano, and alkoxy. In some embodiments, heterocycloalkyl groups can contain one, two, three, or four heteroatoms. One of ordinary skill in the art will recognize that 4-membered heterocycloalkyls typically contain one or two heteroatoms, 5- or 6-membered heterocycloalkyls typically contain one, two, or three heteroatoms, and 7- to 10-membered heterocycloalkyls typically can contain one, two, three, or four heteroatoms.

[0048] "Heterocycloalkylene" refers to a divalent heterocycloalkyl, as defined herein.

[0049] The term "heteroaryl" refers to a monovalent monocyclic aromatic and / or polycyclic aromatic group in which at least one aromatic ring contains one or more heteroatoms independently selected from oxygen, sulfur, and nitrogen. Each ring of a heteroaryl group may contain one or two oxygen atoms, one or two sulfur atoms, and / or one to four nitrogen atoms, provided that the total number of heteroatoms in each ring is four or less and each ring contains at least one carbon atom. In certain embodiments, a heteroaryl has 5 to 20, 5 to 15, or 5 to 10 ring atoms. A heteroaryl may be attached to the remainder of the molecule through a nitrogen or carbon atom. In some embodiments, monocyclic heteroaryl groups include, but are not limited to, furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, triazolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, and triazinyl. Examples of bicyclic heteroaryl groups include, but are not limited to, benzofuranyl, benzimidazolyl, benzisoxazolyl, benzopyranyl, benzothiadiazolyl, benzothiazolyl, benzothienyl, benzotriazolyl, benzoxazolyl, furopyridyl, imidazopyridinyl, imidazothiazolyl, indolizinyl, indolyl, indazolyl, isobenzofuranyl, isobenzothienyl, isoindolyl, isoquinolinyl, naphthyridinyl, oxazolopyridinyl, phthalazinyl, pteridinyl, purinyl, pyridopyridyl, pyrrolopyridyl, quinolinyl, quinoxalinyl, quinazolinyl, thiadiazolopyrimidyl, and thienopyridyl. Examples of tricyclic heteroaryl groups include, but are not limited to, acridinyl, benzindolyl, carbazolyl, dibenzofuranyl, perimidinyl, phenanthrolinyl, phenanthridinyl, phenarsazinyl, phenazinyl, phenothiazinyl, phenoxazinyl, and xanthenyl. In certain embodiments, heteroaryl can also be optionally substituted as described herein. "Substituted heteroaryl" refers to heteroaryl substituted as defined for aryl.

[0050] The term "heteroarylene" refers to a divalent heteroaryl group, as defined herein. A "substituted heteroarylene" is a heteroarylene substituted as defined for aryl.

[0051] The term "heteroarylalkylene" refers to an -alkyl-heteroarylene- or -heteroarylene-alkyl, such as a -C-C alkyl-heteroarylene-, -heteroarylene-C-C alkyl-, or -C-C alkyl-heteroarylene-C-C alkyl- group, where heteroarylene is as defined herein. "Substituted heteroarylalkylene" refers to a heteroarylalkylene group, as defined herein, in which the heteroarylalkylene group is substituted, where aryl is as defined herein. "Substituted C-C alkyl" refers to a C-C alkyl group that is substituted as defined herein for alkyl.

[0052] As used herein, "oxo" refers to =O.

[0053] As used herein, unless otherwise specified, the term "protecting group" refers to a group attached to an oxygen, nitrogen, or phosphorus atom to prevent further reaction of the oxygen, nitrogen, or phosphorus atom, or for other purposes. A wide variety of oxygen and nitrogen protecting groups are known to those skilled in the art of organic synthesis. (See, for example, Greene, et al., Protective Groups in Organic Synthesis, John Wiley and Sons, Fourth Edition, 2006, incorporated herein by reference.)

[0054] "Pharmaceutically acceptable salt" refers to any salt of a compound provided herein that retains its biological properties and is not toxic or otherwise undesirable for pharmaceutical use. Such salts can be derived from a variety of organic and inorganic counterions well known in the art.Such salts include, but are not limited to, (1) salts of organic or inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, sulfamic acid, acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, hexanoic acid, cyclopentylpropionic acid, glycolic acid, glutaric acid, pyruvic acid, lactic acid, malonic acid, succinic acid, sorbic acid, ascorbic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, picric acid, cinnamic acid, mandelic acid, phthalic acid, lauric acid, methanesulfonic acid, and the like. Sulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphoric acid, camphorsulfonic acid, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfuric acid, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, cyclohexylsulfamido or (2) salts formed when an acidic proton present in the parent compound is replaced by (a) a metal ion, such as an alkali metal ion, alkaline earth ion, or aluminum ion, or an alkali metal or alkaline earth metal hydroxide, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, aluminum hydroxide, lithium hydroxide, zinc hydroxide, and barium hydroxide, ammonia, or (b) an organic base, such as an aliphatic, alicyclic, or aromatic organic amine, including, but not limited to, ammonia, methylamine, dimethylamine, diethylamine, picoline, ethanolamine, diethanolamine, triethanolamine, ethylenediamine, lysine, arginine, ornithine, choline, N,N'-dibenzylethylene-diamine, chloroprocaine, procaine, N-benzylphenethylamine, N-methylglucamine piperazine, tris(hydroxymethyl)-aminomethane, tetramethylammonium hydroxide, and the like.

[0055] Pharmaceutically acceptable salts further include, by way of example and not limitation, sodium, potassium, calcium, magnesium, ammonium, and tetraalkylammonium salts, and, if the compound contains a basic functional group, salts of non-toxic organic or inorganic acids, such as hydrohalides, e.g., hydrochlorides and hydrobromides, sulfates, phosphates, sulfamates, nitrates, acetates, trifluoroacetates, trichloroacetates, propionates, hexanoates, cyclopentylpropionates, glycolates, glutarates, pyruvates, lactates, malonates, succinates, sorbates, ascorbates, malates, maleates, fumarates, tartrates, citrates, benzoates, 3-(4-hydroxybenzoyl)benzoates, and the like. Acid salts include hydroxysulfonates, picrates, cinnamates, mandelates, phthalates, laurates, methanesulfonates (mesylates), ethanesulfonates, 1,2-ethanedisulfonates, 2-hydroxyethanesulfonates, benzenesulfonates (besylates), 4-chlorobenzenesulfonates, 2-naphthalenesulfonates, 4-toluenesulfonates, camphorates, camphorsulfonates, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylate, glucoheptonates, 3-phenylpropionates, trimethyl acetate, tert-butyl acetate, lauryl sulfate, gluconates, glutamates, hydroxynaphthoates, salicylates, stearates, cyclohexylsulfamates, quinates, and muconates.

[0056] The terms "substantially free" or "substantially free," with respect to a composition, refer to a composition that contains at least 85%, or 90%, and in certain embodiments 95%, 98%, 99%, or 100% by weight; or in certain embodiments, 95%, 98%, 99%, or 100% of a specified enantiomer or diastereomer of a compound. In certain embodiments, in the methods and compounds provided herein, the compound is substantially free of one of the two enantiomers. In certain embodiments, in the methods and compounds provided herein, the compound is substantially free of one of the two diastereomers. In certain embodiments, in the methods and compounds provided herein, the compound is substantially free of an enantiomer (i.e., a racemate, or a 50:50 mixture of compounds).

[0057] Similarly, the term "isolated" with respect to a composition refers to a composition that contains at least 85%, 90%, 95%, 98%, or 99% to 100% by weight of a compound, with the remainder containing other species, enantiomers, or diastereomers.

[0058] "Solvate" refers to a compound provided herein, or a salt thereof, that further includes a stoichiometric or non-stoichiometric amount of solvent bound by non-covalent intermolecular forces. When the solvent is water, the solvate is a hydrate.

[0059] "Isotopic composition" refers to the amount of each isotope present for a given atom, and "natural isotopic composition" refers to the naturally occurring isotopic composition or abundance for a given atom. Atoms with natural isotopic composition may also be referred to herein as "non-enriched" atoms. Unless otherwise specified, atoms of compounds described herein are meant to represent any stable isotope of that atom. For example, unless otherwise specified, if a position is specifically designated as hydrogen (H), it is understood that the position has hydrogen at its natural isotopic composition.

[0060] "Isotopic enrichment" refers to the proportion of a given atom in a molecule that incorporates a certain amount of a particular isotope, instead of the atom's natural isotopic abundance. For example, a deuterium (D) enrichment of 1% at a given position means that 1% of the molecules in a given sample contain deuterium at that position. Since the distribution of naturally occurring deuterium is approximately 0.0156%, the deuterium enrichment at any position of a compound synthesized using non-enriched starting materials is approximately 0.0156%. The isotopic enrichment of the compounds provided herein can be determined using conventional analytical methods known to those skilled in the art, including mass spectrometry and nuclear magnetic resonance spectroscopy.

[0061] "Isotopically enriched" refers to an atom having an isotopic composition other than the natural isotopic composition of that atom. "Isotopically enriched" may also refer to a compound containing at least one atom having an isotopic composition other than the natural isotopic composition of that atom.

[0062] As used herein, "alkyl," "alkylene," "alkylamino," "dialkylamino," "cycloalkyl," "aryl," "arylene," "alkoxy," "amino," "carboxyl," "heterocycloalkyl," "heteroaryl," "heteroarylene," "carboxyl," and "amino acid" groups optionally contain deuterium (D) at one or more positions where a hydrogen (H) atom would be present, and the deuterium composition of that atom(s) is other than the natural isotopic composition.

[0063] Also, as used herein, "alkyl," "alkylene," "alkylamino," "dialkylamino," "cycloalkyl," "aryl," "arylene," "alkoxy," "amino," "carboxyl," "heterocycloalkyl," "heteroaryl," "heteroarylene," "carboxyl," and "amino acid" groups optionally contain amounts of carbon-13( 13 C).

[0064] As used herein, "EC 50The term "elicits a dose, concentration, or amount of a particular test compound that elicits a dose-dependent response at 50% of the maximal expression of the particular response induced, elicited, or potentiated by the particular test compound."

[0065] As used herein, unless otherwise specified, "IC 50 The term "50% inhibition" refers to an amount, concentration, or dose of a particular test compound that achieves 50% inhibition of a maximal response in an assay that measures the maximal response.

[0066] As used herein, the terms "subject" and "patient" are used interchangeably. The terms "subject" and "subjects" refer to animals, e.g., mammals, including non-primates (e.g., cows, pigs, horses, cats, dogs, rats, and mice) and primates (e.g., monkeys such as cynomolgus monkeys, chimpanzees, and humans), and in certain embodiments, humans. In certain embodiments, the subject is a farm animal (e.g., a horse, cow, pig, etc.) or a pet (e.g., a dog or cat). In certain embodiments, the subject is a human.

[0067] As used herein, the term "therapeutic agent(s)" refers to any agent(s) that can be used in the treatment or prevention of a disorder or one or more symptoms thereof. In certain embodiments, the term "therapeutic agent" includes the compounds provided herein. In certain embodiments, a therapeutic agent is an agent that is known to be, has been used, or is currently being used to be useful in the treatment or prevention of a disorder or one or more symptoms thereof.

[0068] "Therapeutically effective amount" means the amount of a compound or composition that, when administered to a subject for treating a condition, is sufficient to effect such treatment for that condition. A "therapeutically effective amount" can vary depending, inter alia, on the compound, the disease or disorder and its severity, and the age, weight, etc., of the subject being treated.

[0069] "Treating" or "treatment" of any disease or disorder refers, in certain embodiments, to ameliorating the disease or disorder present in a subject. In another embodiment, "treating" or "treatment" includes improving at least one physical parameter, which may be difficult for a subject to discern. In yet another embodiment, "treating" or "treatment" includes modulating the disease or disorder, either physically (e.g., stabilization of a discernible symptom), physiologically (e.g., stabilization of a physiological parameter), or both. In yet another embodiment, "treating" or "treatment" includes delaying or preventing the onset of the disease or disorder, or delaying or preventing the recurrence of the disease or disorder. In yet another embodiment, "treating" or "treatment" includes reducing or eliminating either the disease or disorder, or delaying the progression of the disease or disorder, or one or more symptoms of the disease or disorder, or reducing the severity of the disease or disorder, or the severity of one or more symptoms of the disease or disorder.

[0070] As used herein, the term "prophylactic agent(s)" refers to any agent(s) that can be used in the prevention of a disorder or one or more symptoms thereof. In certain embodiments, the term "prophylactic agent" includes the compounds provided herein. In certain other embodiments, the term "prophylactic agent" does not refer to the compounds provided herein. For example, a prophylactic agent is an agent known to be useful for preventing or hindering the onset, development, progression, and / or severity of a disorder, or that has been used or is currently being used to arrest the onset, development, progression, and / or severity of a disorder.

[0071] As used herein, the phrase "prophylactically effective amount" refers to an amount of a therapy (e.g., a prophylactic agent) sufficient to prevent or reduce the onset, recurrence, or development of one or more symptoms associated with a disorder, or to enhance or improve the prophylactic effects of another therapy (e.g., another prophylactic agent). Compounds of formulae (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII)

[0072] Provided herein is a GLP-1 receptor compound that is useful for regulating one or more properties of GLP-1 receptor.This compound can be prepared as described herein and used for treatment or diagnosis.In certain embodiments, this treatment is the treatment of metabolic disease or metabolic condition.In certain embodiments, this treatment is the treatment of type 2 diabetes.

[0073] The embodiments described herein include the recited compounds, as well as pharmaceutically acceptable salts, hydrates, solvates, stereoisomers, tautomers, and / or mixtures thereof.

[0074] In certain embodiments, there is provided a compound of Formula (I), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof; wherein A is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, -NMe2, or -CF3; ring B is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; ring C is further unsubstituted, further substituted, and / or bridged; and D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and;L 1 is selected from the group consisting of a bond, —O—, —CH—, —NH—, —N(Me)—, —N(Et)—, —OCH—, —OC(H,Me)—, —CHO—, —NHCH—, —N(Me)CH—, and —SONH—; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; L 4 does not exist or L 4 L 1 and together with rings A and B form a fused tricyclic ring, and L 5 does not exist; and L 5 does not exist or L 5 L 2 and together with rings B and C form a fused tricyclic ring, and L 4 does not exist;R 4 is an unsubstituted alkyl, a substituted alkyl, an unsubstituted arylalkylene, a substituted arylalkylene, an unsubstituted heteroalkyl, a substituted heteroalkyl, an unsubstituted heteroarylalkylene, a substituted heteroarylalkylene, an unsubstituted heterocycloalkylalkylene, or a substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO- and R 11 R 12 N-; 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; and R 13 is hydrogen or alkyl. In certain embodiments, L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-.

[0075] In certain embodiments of Formula (I), L 1 is -CH2O-, and L 4 does not exist, and L 5 If does not exist, then L 2 is -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, CHF-, -CHOH-, -NH-, -N(Me)-, or [ka] or L 3 is —C(O)—, or both. In certain embodiments, L 1 is -CH2O-, and L 4 does not exist, and L 5 If does not exist, then L 2 is -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, or [ka] In certain embodiments, L 1 is -CH2O-, and L 4 does not exist and L 5 If does not exist, then L 3 is —C(O)—. In certain embodiments, L 1 If is -CH2O-, L 4 L 1 and together with ring A and ring B form a fused tricyclic ring. 1 When is -CH2O-, L 5 L 2 and together with rings B and C form a fused tricyclic ring. 1 is —CH 2 O—, then Ring C is substituted or unsubstituted azetidinyl, substituted or unsubstituted pyrrolidinyl, or substituted or unsubstituted piperidinyl.

[0076] In certain embodiments, A is a ring selected from phenyl and cyclohexyl. In certain embodiments, ring C is selected from piperidine and piperazine. In certain embodiments, ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran. In certain embodiments, A is phenyl and ring C is piperazine. In certain embodiments, A is phenyl and ring C is piperidine. In certain embodiments, A is phenyl and ring C is piperazine, and ring B is phenyl. In certain embodiments, A is phenyl and ring C is piperazine, and ring B is furan. In certain embodiments, A is phenyl and ring C is piperidine, and ring B is phenyl. In certain embodiments, A is phenyl and ring C is piperidine, and ring B is furan.

[0077] In certain embodiments, A is a ring selected from phenyl and cyclohexyl. In certain embodiments, ring C is selected from substituted piperidine, azetidine, and pyrrolidine. In certain embodiments, ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran. In certain embodiments, A is phenyl and ring C is piperazine. In certain embodiments, A is phenyl and ring C is piperidine. In certain embodiments, A is phenyl and ring C is substituted piperidine. In certain embodiments, A is phenyl and ring C is azetidine. In certain embodiments, A is phenyl and ring C is pyrrolidine. In certain embodiments, A is phenyl, ring C is piperazine, and ring B is phenyl. In certain embodiments, A is phenyl, ring C is piperazine, and ring B is furan. In certain embodiments, A is phenyl, ring C is piperidine, and ring B is phenyl. In certain embodiments, A is phenyl, Ring C is piperidine, and Ring B is furan. In certain embodiments, A is phenyl, Ring C is substituted piperidine, and Ring B is phenyl. In certain embodiments, A is phenyl, Ring C is substituted piperidine, and Ring B is furan. In certain embodiments, A is phenyl, Ring C is azetidine, and Ring B is phenyl. In certain embodiments, A is phenyl, Ring C is azetidine, and Ring B is furan. In certain embodiments, A is phenyl, Ring C is pyrrolidine, and Ring B is phenyl. In certain embodiments, A is phenyl, Ring C is pyrrolidine, and Ring B is furan.

[0078] In certain embodiments, compounds of Formula (Ia), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, are provided; wherein A is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, -NMe2, or -CF3; ring B is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; ring C is further unsubstituted, further substituted, and / or bridged; and D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 W is N, CH, or C; when W is CH, adjacent dashed lines represent a single bond; when W is C, adjacent dashed lines represent a double bond, e.g., L 2 is -C(H)=;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; L 4 does not exist or L 4 L 1 and together with rings A and B form a fused tricyclic ring, and L 5 does not exist;L 5 does not exist or L 5 L 2 and together with rings B and C form a fused tricyclic ring, and L 4 does not exist;R 4is an unsubstituted alkyl, a substituted alkyl, an unsubstituted arylalkylene, a substituted arylalkylene, an unsubstituted heteroalkyl, a substituted heteroalkyl, an unsubstituted heteroarylalkylene, a substituted heteroarylalkylene, an unsubstituted heterocycloalkylalkylene, or a substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO- and R 11 R 12 N-; 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; R 13 is hydrogen or alkyl. In certain embodiments, L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-.

[0079] In certain embodiments of Formula (Ia), L 1 is -CH2O-, and L 4 does not exist and L 5 If does not exist, then L 2 is -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, or [ka] or L 3 is —C(O)—, or both. In certain embodiments, L 1 is -CH2O-, and L 4 does not exist and L 5 If does not exist, then L 2 is -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, or [ka] In certain embodiments, L 1 is -CH2O-, and L 4 does not exist and L 5 If does not exist, then L 2 is -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, or [ka] In certain embodiments, L 1 is -CH2O-, and L 4 does not exist and L 5 If does not exist, then L 3 is —C(O)—. In certain embodiments, L 1 If is -CH2O-, L 4 L 1 and together with ring A and ring B form a fused tricyclic ring. 1 When is -CH2O-, L 5 is L 2 and together with rings B and C form a fused tricyclic ring.

[0080] In certain embodiments, A is a ring selected from phenyl and cyclohexyl. In certain embodiments, ring C is selected from piperidine and piperazine. In certain embodiments, ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran. In certain embodiments, A is phenyl and ring C is piperazine. In certain embodiments, A is phenyl and ring C is piperidine. In certain embodiments, A is phenyl and ring C is piperazine, and ring B is phenyl. In certain embodiments, A is phenyl and ring C is piperazine, and ring B is furan. In certain embodiments, A is phenyl and ring C is piperidine, and ring B is phenyl. In certain embodiments, A is phenyl and ring C is piperidine, and ring B is phenyl. In certain embodiments, A is phenyl and ring C is piperidine, and ring B is furan.

[0081] In certain embodiments, there is provided a compound of Formula (XXX), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof; wherein W is N, CH, or C; when W is CH, adjacent dashed lines represent a single bond; when W is C, adjacent one dashed line represents a double bond, e.g., L 2 is -C(H) =;A 1 , A 2 , A 3 , A 4 , and A 5 0, 1, or 2 of these are N, and the rest are CH or CR 1 and;B 1 , B 2 , B 3 , and B 4 0, 1, or 2 of these are N, and the rest are CH or CR 2 And ;D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and;L 1is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is an unsubstituted alkyl, a substituted alkyl, an unsubstituted heteroalkyl, a substituted heteroalkyl, an unsubstituted heterocycloalkylalkylene, or a substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO- and R 11 R12 N-; 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; R 13 is hydrogen or alkyl; and o is an integer from 0 to 4. In certain embodiments, the compound of Formula (XXX) is selected from compounds 82, 83, 91, 92, and 110 in Table 1.

[0082] In certain embodiments, there is provided a compound of formula (XXXI), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof; wherein W is N, CH, or C; when W is CH, the adjacent dashed line indicates a single atom; A 1 , A 2 , A 3 , A 4 , and A 5 0, 1, or 2 of these are N, and the rest are CH or CR 1 is. D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and; Each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 independently selected from the group consisting of NCO-; L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; Each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 independently selected from the group consisting of NCO-; R 4 is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; Each R 6 is independently selected from the group consisting of F and methyl; R 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; R 13 is hydrogen or alkyl; and o is 1, 2, 3, or 4. In certain embodiments, the compound of Formula (XXXI) is selected from compounds 97 and 107 in Table 1.

[0083] In certain embodiments, the compound of Formula (I) may be represented by Formula (IIa), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] where A 1 , A 2 , A 3 , A4 , and A 5 0, 1, or 2 of which are N, and the rest are CH or CR 1 and;B 1 , B 2 , B 3 , and B 4 0, 1, or 2 of these are N, and the rest are CH or CR 2 wherein Formula IIaB 4 does not exist ;D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is an unsubstituted alkyl, a substituted alkyl, an unsubstituted arylalkylene, a substituted arylalkylene, a heteroalkyl, a substituted heteroalkyl, an unsubstituted heteroarylalkylene, a substituted heteroarylalkylene, an unsubstituted heterocycloalkylalkylene, or a substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6is independently selected from the group consisting of F and methyl; each R 11 is hydrogen or alkyl, and each R 12は is hydrogen or alkyl, and each R 13 is hydrogen or alkyl, and o is 1, 2, 3, or 4.

[0084] In certain embodiments, the compound of Formula (I) may be represented by Formula (IIb), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, A 1 , A 2 , A 3 , A 4 , and A 5 0, 1, or 2 of which are N, and the rest are CH or CR 1 and;B 1 , B 2 , B 3 , and B 4 0, 1, or 2 of these are N, and the rest are CH or CR 2 wherein in formula IIb, B 4 does not exist ;D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4is an unsubstituted alkyl, a substituted alkyl, an unsubstituted arylalkylene, a substituted arylalkylene, a heteroalkyl, a substituted heteroalkyl, an unsubstituted heteroarylalkylene, a substituted heteroarylalkylene, an unsubstituted heterocycloalkylalkylene, or a substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is independently selected from the group consisting of F and methyl; each R 11 is hydrogen or alkyl, and each R 12 is hydrogen or alkyl, and each R 13 is hydrogen or alkyl, and o is 1, 2, 3, or 4.

[0085] In certain embodiments, the compound of Formula (I) may be represented by Formula (IIc), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, A 1 , A 2 , A 3 , A 4 , and A 5 0, 1, or 2 of which are N, and the rest are CH or CR 1 and;B 1 , B 2 , B 3 , and B 4 0, 1, or 2 of these are N, and the rest are CH or CR 2 wherein in formula IIc, B 4 does not exist ;D 1 , D 2 , and D 30, 1, or 2 of these are N, and the rest are CH or CR 6 and each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is an unsubstituted alkyl, a substituted alkyl, an unsubstituted arylalkylene, a substituted arylalkylene, a heteroalkyl, a substituted heteroalkyl, an unsubstituted heteroarylalkylene, a substituted heteroarylalkylene, an unsubstituted heterocycloalkylalkylene, or a substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is independently selected from the group consisting of F and methyl; each R 11 is hydrogen or alkyl, and each R 12 is hydrogen or alkyl, and each R 13 is hydrogen or alkyl; R 14 is hydrogen, cyano, halo, hydroxyl, or methyl; and o is 1, 2, 3, or 4.

[0086] In certain embodiments, the compound of Formula (I) may be represented by Formula (IId), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, A 1 , A 2 , A 3 , A 4 , and A 5 0, 1, or 2 of which are N, and the rest are CH or CR 1 and;B 1 , B 2 , B 3 , and B 4 0, 1, or 2 of these are N, and the rest are CH or CR 2 wherein in formula IId, B 4 does not exist ;D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is an unsubstituted alkyl, a substituted alkyl, an unsubstituted arylalkylene, a substituted arylalkylene, a heteroalkyl, a substituted heteroalkyl, an unsubstituted heteroarylalkylene, a substituted heteroarylalkylene, an unsubstituted heterocycloalkylalkylene, or a substituted heterocycloalkylalkylene; R 5-COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is independently selected from the group consisting of F and methyl; each R 11 is hydrogen or alkyl, and each R 12 is hydrogen or alkyl, and each R 13 is hydrogen or alkyl; R 14 is hydrogen, cyano, halo, hydroxyl, or methyl; and o is 1, 2, 3, or 4.

[0087] In certain embodiments, the compound of Formula (I) may be represented by Formula (IIg), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, A 1 , A 2 , A 3 , A 4 , and A 5 0, 1, or 2 of which are N, and the rest are CH or CR 1 and;B 1 , B 2 , B 3 , and B 4 0, 1, or 2 of these are N, and the rest are CH or CR 2 wherein in formula IIg, B 4 does not exist ;D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is an unsubstituted alkyl, a substituted alkyl, an unsubstituted arylalkylene, a substituted arylalkylene, a heteroalkyl, a substituted heteroalkyl, an unsubstituted heteroarylalkylene, a substituted heteroarylalkylene, an unsubstituted heterocycloalkylalkylene, or a substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is independently selected from the group consisting of F and methyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl.

[0088] In certain embodiments, the compound of Formula (I) may be represented by Formula (IIh), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, A 1 , A 2 , A 3 , A 4 , and A 50, 1, or 2 of which are N, and the rest are CH or CR 1 and;B 1 , B 2 , B 3 , and B 4 0, 1, or 2 of these are N, and the rest are CH or CR 2 wherein in formula IIg, B 4 does not exist ;D 1 , D 2 , and D 3 0, 1, or 2 of these are N, and the rest are CH or CR 6 and each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is an unsubstituted alkyl, a substituted alkyl, an unsubstituted arylalkylene, a substituted arylalkylene, a heteroalkyl, a substituted heteroalkyl, an unsubstituted heteroarylalkylene, a substituted heteroarylalkylene, an unsubstituted heterocycloalkylalkylene, or a substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is independently selected from the group consisting of F and methyl; each R11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl.

[0089] In certain embodiments, there is provided a compound of formula (III), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] where W is N, CR 14 , or C and W is CR 14 When W is C, the adjacent dashed line represents a double bond, or when L 2 -C(H) = ;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -NH-, N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of Formula (III) is selected from the group consisting of compounds 2, 3, 5-7, 10-18, 21-23, 25, 29, 32, 33, 35, 45, 46, 48, 50-52, 54, 56-58, 64-70, 75-80, 86, 89, 93, 95, 98, 100, 103-105, 111, 112, 115, 116, 122, 126, 128, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 1 , 130-133, 135, 137, 148, 149, 151, 157-159, 161, 162, 165, 166, 174, 187, 188, 202-208, 215-217, 221, 231, 232, 242, 243, 254, 255, 260, 263, 288, 294, 301, 318, 319, and 321.

[0090] In certain embodiments, there is provided a compound of formula (IIIa), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl, and each R 12 is hydrogen or alkyl, and each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of Formula (IIIa) is selected from compounds 103, 104, 111, 116, 126, 130-133, 135, 137, 148, 149, 151, 157-159, 161, 162, 165, 166, 174, 187, 188, 202-208, 215-217, 221, 231, 232, 242, 243, 254, 255, 260, 263, 288, 294, 301, 318, 319, and 321 in Table 1.

[0091] In certain embodiments, there is provided a compound of formula (IV), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C and W is CR14 When W is C, the adjacent dashed line represents a double bond, or when L 2 -C(H) = ;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (IV) is selected from compounds 8, 9, 19, 20, 24, 26, 30, 31, 36-43, 47, 49, 55, 59, 63, 72-74, 81, 84, 94, 96, 108, and 109 in Table 1.

[0092] In certain embodiments, there is provided a compound of formula (V), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] where W is N, CR 14 , or C; W is CR 14 When W is C, the adjacent dashed line represents a double bond, or when L 2 -C(H) = ;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (V) is selected from compound 71 in Table 1.

[0093] In certain embodiments, there is provided a compound of formula (VI), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is selected from the group consisting of —CH— or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (VI) is selected from compounds 34, 62, and 331 in Table 1.

[0094] In certain embodiments, there is provided a compound of formula (VII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C; W is CR 14When W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is selected from the group consisting of —CH—, or —C(O)—; 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (VII) is selected from compounds 60, 102, 113, 124, 136, 138, 141, 144, 154, 156, 160, 186, 214, 256, 278, and 279 in Table 1.

[0095] In certain embodiments, there is provided a compound of formula (VIII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 when W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=;L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH— or —C(O)—; each R 1is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (VIII) is selected from compound 44 in Table 1.

[0096] In certain embodiments, there is provided a compound of formula (IX), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 when W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH—, or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4is independently selected from the group consisting of alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of Formula (IX) is selected from compounds 27 and 28 in Table 1.

[0097] In certain embodiments, there is provided a compound of formula (X), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C; W is CR 14when W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH—, or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is independently selected from the group consisting of alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (X) is selected from compounds 4, 272, and 284 in Table 1.

[0098] In certain embodiments, there is provided a compound of formula (XI), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 when W is C, the adjacent dashed line represents a double bond, or when L 2 -C(H) = ;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 3 is —CH— or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (XI) is selected from compounds 53, 90, 121, 142, and 143 in Table 1.

[0099] In certain embodiments, there is provided a compound of formula (XII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 when W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH—, or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (XII) is compound 108 in Table 1.

[0100] In certain embodiments, there is provided a compound of formula (XIII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C; W is CR 14when W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH—, or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (XIII) is selected from compounds 88, 178, and 179 in Table 1.

[0101] In certain embodiments, there is provided a compound of formula (XIV), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 when W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L3 is —CH—, or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (XIV) is selected from compounds 85, 139, and 220 in Table 1.

[0102] In certain embodiments, there is provided a compound of formula (XV), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 when W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH—, or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of Formula (XV) is selected from compounds 101, 114, 118, 120, 123, 140, 146, 152, 153, 198-200, 246-249, 251-253, 264, 268-271, 285, 290, 291, 330, and 347 in Table 1.

[0103] In certain embodiments, there is provided a compound of formula (XVI), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 when W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH— or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5-COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, R 14 is CHF or CHOH. In certain embodiments, the compound of Formula (XVI) is selected from compounds 99, 128, 145, 150, 155, 163, 164, 168-171, 182, 183, 189, 227, 230, 239-241, 250, 257-259, 265-267, 274-277, 280, 283, 287, 292, 295, 297, 299, 308, 316, 321, 322, 333, 335, 337, 345, 346, 352, 354, 356-358, 362-364, 366-368, 378, and 380 in Table 1.

[0104] In certain embodiments, there is provided a compound of formula (XVIa), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka]

[0105] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is selected from the group consisting of —CH—, or —C(O)—; 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R13 is hydrogen or alkyl; R 14 is hydrogen, cyano, halo, hydroxyl, or methyl; n is an integer from 0 to 5; and m is an integer from 0 to 4. In certain embodiments, L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of Formula (XVI) is selected from compounds 128, 145, 168-171, 182, 183, 227, 230, 239-241, 250, 257-259, 265-267, 274-277, 280, 283, 287, 292, 295, 297, 299, 302, 308, 316, 321, 322, 333, 335-337, 344-346, 352, 354, 356-359, 362-368, 378, and 380 in Table 1.

[0106] In certain embodiments, there is provided a compound of formula (XVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 3 is —CH—, or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (XVII) is selected from compound 106 in Table 1.

[0107] In certain embodiments, there is provided a compound of formula (XVIII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka]

[0108] In the formula, W is N, CR 14 , or C; W is CR 14 when W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH—, or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4is independently selected from the group consisting of alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of formula (XVIII) is compound 87 in Table 1.

[0109] In certain embodiments, there is provided a compound of formula (XXV), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, W is N, CR 14 , or C and W is CR 14When W is C, the adjacent dashed line indicates a double bond, or when L 2 -C(H) = ;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH—, or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12is hydrogen or alkyl; each R 13 is hydrogen or alkyl; R 14 is hydrogen, cyano, halo, hydroxyl, or methyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4; p is an integer from 0 or 1; and q is an integer from 0 or 1. In certain embodiments, p is 0; and q is 0. In certain embodiments, p is 1; and q is 0. In certain embodiments, p is 0; and q is 1. In certain embodiments, p is 1; and q is 1. In certain embodiments, L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, the compound of Formula (XXV) is compound 286 in Table 1.

[0110] In certain embodiments, there is provided a compound of formula (XXVI), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka]

[0111] In the formula, W is N, CR 14 , or C; W is CR 14 when W is C, the adjacent dashed line represents a double bond, or when L 2 is -C(H)=;L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH— or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of Formula (XXVI) is selected from compounds 261, 262, 296, 304, 306, 307, 311, 313, 315, 325, 326, 331, 338, 340, 342, 343, 348, 353, 354, 355, 369, 374, 376, 475, 481, 483, 485, 489, 490, 492, 493, 495, 498, 504, 510, 512, 514, and 515 in Table 1.

[0112] In certain embodiments, there is provided a compound of formula (XXVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] where A is -NMe2 or -N(CH3)cyclohexane; 1 does not exist; W is N, CR 14 , or C; W is CR 14 and the adjacent dashed line represents a single bond; if W is C, the adjacent dashed line represents a double bond, or L 2 -C(H) = ;L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is selected from the group consisting of —CH— or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, the compound of formula (XXVII) is selected from compounds 1 and 62 in Table 1.

[0113] In certain embodiments, there is provided a compound of formula (XXXIX), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO- and R 11 R 12 N-; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4; and r is an integer from 0 to 3. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, each R 6 is independently selected from the group consisting of F and methyl. In certain embodiments, each R 6 is F. In certain embodiments, the compound of Formula (XXXIX) is selected from compounds 224, 300, 303, 309, 310, 317, and 320 in Table 1.

[0114] In certain embodiments, there is provided a compound of formula (XL), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO- and R 11 R 12 N-; each R 11 is hydrogen or alkyl; each R 12is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4; and r is an integer from 0 to 3. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, each R 6 is independently selected from the group consisting of F and methyl. In certain embodiments, each R 6 is F. In certain embodiments, the compound of formula (XL) is selected from compounds 302, 325, 336, 344, 359, and 365 in Table 1.

[0115] In certain embodiments, there is provided a compound of formula (XLI), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO- and R 11 R 12 N-; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4; and r is an integer from 0 to 3. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, each R6 is independently selected from the group consisting of F and methyl. In certain embodiments, each R 6 is F. In certain embodiments, each R 6 is methyl. In certain embodiments, the compound of Formula (XLI) is selected from compounds 302, 325, 336, 344, 359, 365, 478, 482, 484, 494, 496, 500-503, 505, 508, 509, and 511 in Table 1.

[0116] In certain embodiments, there is provided a compound of formula (XLII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH— or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is —O—. In certain embodiments, the compound of Formula (XLII) is selected from compounds 370, 371, 373, 375, 377, 378, 486, and 513 in Table 1.

[0117] In certain embodiments, there is provided a compound of formula (XLIII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R11 R 12 NCO- and R 11 R 12 N-; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4; and r is an integer from 0 to 3. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is —O—. In certain embodiments, each R 6 is independently selected from the group consisting of F and methyl. In certain embodiments, each R 6 is F. In certain embodiments, each R 6 is methyl. In certain embodiments, the compound of formula (XLIII) is selected from compounds 487 and 488 in Table 1.

[0118] In certain embodiments, there is provided a compound of formula (XLII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH— or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is —O—. In certain embodiments, the compound of formula (XLIV) is compound 372 in Table 1.

[0119] In certain embodiments, there is provided a compound of Formula (XLV), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH— or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is —O—. In certain embodiments, the compound of formula (XLV) is compound 379 in Table 1.

[0120] In certain embodiments, there is provided a compound of formula (XLVI), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is —CH— or —C(O)—; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, L 2 is —O—. In certain embodiments, the compound of formula (XLVI) is selected from compounds 125 and 129 in Table 1.

[0121] In certain embodiments, there is provided a compound of formula (XLI), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: [ka] In the formula, L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CHO-, -NHCH2-, -N(Me)CH2-, and -SONH-; L 2 represents a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] selected from the group consisting of: L 3 is -CH2- or -C(O)-; each R 1 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 2 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; each R 3 is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11 R 12 NCO-; 4is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and tetrazolyl; each R 6 is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R 11 R 12 NCO- and R 11 R 12 N-; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4; and r is an integer from 0 to 3. In certain embodiments, L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] In certain embodiments, each R 6 is independently selected from the group consisting of F and methyl. In certain embodiments, each R 6 is F. In certain embodiments, each R 6 is methyl. In a particular embodiment, the compound of formula (XLVII) is compound 491 in Table 1.

[0122] In certain embodiments, a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, is provided, wherein each R 2 and R 3 is H or F.

[0123] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein m is 0; and o is 0.

[0124] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein W is N or CH.

[0125] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein W is C.

[0126] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein W is CH.

[0127] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein W is N.

[0128] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein W is CR 14 is.

[0129] In certain embodiments, a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, is provided, wherein R 4 is selected from the group consisting of oxetan-2-yl-methyl, (1-ethyl-1H-imidazol-5-yl)-methyl, oxelan-3-yl-methyl and 1,3-oxazol-2-yl-methyl.

[0130] In certain embodiments, there is provided a compound of any of Formulas (XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4 is selected from the group consisting of oxetan-2-yl-methyl, and (1-ethyl-1H-imidazol-5-yl)-methyl.

[0131] In certain embodiments, there is provided a compound of any of Formulas (XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R4 is oxetan-2-yl-methyl.

[0132] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4 is (2S)-oxetan-2-yl-methyl.

[0133] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl.

[0134] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4 is selected from the group consisting of (S)-but-4-yl-1,3-diol, butan-1-yl-one, 1-(cyanomethyl)-cycloprop-1-yl-methyl, 1-(fluoromethyl)-cycloprop-1-yl-methyl, 1-hydroxyl-cycloprop-1-yl-methyl, isoxazol-5-yl-methyl, (1-methyl-1H-imidazol-5-yl)-methyl, 1-methoxy-cycloprop-1-yl-methyl, methoxyethan-2-yl, 1-(2-methoxyethyl)-cycloprop-1-yl-methyl, and 2-oxabicyclo[2.1.1]hex-1-yl-methyl.

[0135] In certain embodiments, compounds of formula (XXX), or pharmaceutical salts, tautomers, stereoisomers, and / or mixtures of stereoisomers thereof, are provided, wherein R 4 is H.

[0136] In certain embodiments, a compound of formula (XXX), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, is provided, wherein R 4 is selected from the group consisting of oxelan-3-yl-methyl and 1,3-oxazol-2-yl-methyl.

[0137] In certain embodiments, compounds of formula (XXX) and (XXXI), or pharmaceutical salts, tautomers, stereoisomers, and / or mixtures of stereoisomers thereof, are provided, wherein R 4 is (3R)-oxelan-3-yl-methyl.

[0138] In certain embodiments, compounds of formula (XXX) and (XXXI), or pharmaceutical salts, tautomers, stereoisomers, and / or mixtures of stereoisomers thereof, are provided, wherein R 4 is 1,3-oxazol-2-yl-methyl.

[0139] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 5 is -COOH, or -COOMe.

[0140] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 5 is -COOH.

[0141] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 5 is tetrazolyl.

[0142] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 5 is 1H-1,2,3,4-tetrazol-5-yl.

[0143] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is —CH2—, —C(O)—, or —SO2—.

[0144] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is a bond, —C(O)—, —CH—, —C(H)═, —SO—, —O—, —CF—, —CHF—, or —CH(OH)—.

[0145] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2is -CH= or -O-.

[0146] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is —CF2—, —CHF—, or —CH(OH)—.

[0147] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is —NH— or —N(Me)—.

[0148] In certain embodiments, compounds of formula (XXX), or pharmaceutical salts, tautomers, stereoisomers, and / or mixtures of stereoisomers thereof, are provided, wherein L 2 is a bond.

[0149] In certain embodiments, compounds of formula (XXXI), or pharmaceutical salts, tautomers, stereoisomers, and / or mixtures of stereoisomers thereof, are provided, wherein L 2 is -CH2-.

[0150] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 3 is -CH2-.

[0151] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 3 is -C(O)-.

[0152] In certain embodiments, compounds of formula (XXX), or pharmaceutical salts, tautomers, stereoisomers, and / or mixtures of stereoisomers thereof, are provided, wherein L 1 is -CH2O- or -OCH2-.

[0153] In certain embodiments, compounds of formula (XXXI), or pharmaceutical salts, tautomers, stereoisomers, and / or mixtures of stereoisomers thereof, are provided, wherein L 1 is -CH2O- or -OCH2.

[0154] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1 is -CH2O-; and L 2 is -CH2- or -CO-.

[0155] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1 is -CH2O-; and L 3 is -C(O)-.

[0156] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein: L 1 is -O-.

[0157] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1 is -CH2-.

[0158] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1 is -NH-.

[0159] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1 is -N(Me)-.

[0160] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1 is -N(Et)-.

[0161] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1 is -OCH2-.

[0162] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein: L 1 is -OC(H,Me)-.

[0163] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1 is -CH2O-.

[0164] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1 is -NHCH2-.

[0165] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1 is -N(Me)CH2-.

[0166] In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1 is -SO2NH-.

[0167] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-; and L 2In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is —C(O)—; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLICI), L 1 is -O-;L 2 is -N(Me)-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 is -O-;L 2 is -C(O)-, and L 3 is -CH2- and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-; and R 2 and R 3 and each represent H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-, and L 3 is -CH2-; R 2 and R 3 are H, and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is —COOH. Formulas (I) to (XVIII), (XXV) to (X In certain embodiments of any of XVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-, and L 3 is -CH2- and R 2 and R 3 are H and R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazol-5-yl. Any specific group of formulae (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII) In the embodiment, L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R 1 may be selected from H, Cl, F, Me, —CF, —OMe, —CN, —C(O)NMe, alkyl, propyl, isopropyl, and cyclopropyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is (3R)-azetidin-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (S)-but-4-yl-1,3-diol. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIIV), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is -N(Me)-.

[0168] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; and L2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is —C(O)—; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), L 1 is -CH2O-; L 2 is -CH2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -CH2O-; L 2 is -N(Me)--; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3 is -CH2-; and R 2 and R 3 and each represent H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; and R 2 and R 3 and each represent H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; and R2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; R2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; R2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2- and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H and R 4is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; and R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; and R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazolyl In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R 1 may be selected from H, Cl, F, Me, —CF, —OMe, —CN, —C(O)NMe, alkyl, propyl, isopropyl, and cyclopropyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3R)-azetidin-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (S)-but-4-yl-1,3-diol. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is -N(Me)-.

[0169] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), L 1 is -OCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is —C(O)—; and L 3In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -NH-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -N(Me)-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(O)-; L 3 is -CH2-; and R 2 and R 3and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -OCH2-; L 2 is -N(Me)-; L 3 is -CH2-; and R 2 and R 3and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 teeth In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; R2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -OCH2-; L2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), , L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R 1 may be selected from H, Cl, F, Me, —CF, —OMe, —CN, —C(O)NMe, alkyl, propyl, isopropyl, and cyclopropyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is (3R)-azetidin-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is -N(Me)-.

[0170] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-, and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-, and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), L 1 is -NH-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; and L 2In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -NH-; L 2 is —C(O)—; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -CH2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(H)=; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -SO2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -NH-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -N(Me)-; and L 3In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(O)-, and L 3 is -CH2- and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -CH2-; L 3 is -CH2-; and R 2 and R 3 and each represent H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(H)=;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -SO2-;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -NH-; L 3 is -CH2-; and R 2 and R 3and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -N(Me)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl ; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -NH-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is, is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; And R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R 1 may be selected from H, Cl, F, Me, —CF, —OMe, —CN, —C(O)NMe, alkyl, propyl, isopropyl, and cyclopropyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is (3R)-azetidin-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 , 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R4 is 1-(fluoromethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is -N(Me)-.

[0171] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-, and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -N(Me)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is —C(O)—; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -CH2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(H)=; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -SO2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -NH-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -N(Me)-; and L 3In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(O)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -CH2-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(H)=;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -SO2-;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -N(Me)-; L 2 is -NH-; L 3 is -CH2-; and R 2 and R 3and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -N(Me)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -N(Me)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -CH2-; L 3 is -CH2-; R2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -N(Me)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XVII), L 1 is -N(Me)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -CH2-; L3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), L 1 is -N(Me)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 is -N(Me)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R 1 may be selected from H, Cl, F, Me, —CF, —OMe, —CN, —C(O)NMe, alkyl, propyl, isopropyl, and cyclopropyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3R)-azetidin-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is -N(Me)-.

[0172] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -N(Et)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is —C(O)—; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -CH2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(H)=; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -SO2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -NH-; and L 3In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -N(Me)-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(O)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -CH2-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(H)=;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -SO2-;L 3 is -CH2-; and R 2 and R 3and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -NH-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -N(Me)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(H)=;L 3is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIVI), L 1 is -N(Et)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -N(Et)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 teeth, -N(Et)-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(O)-; L 3 is -CH2-; R 2and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -N(Et)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazol-5-yl. Formulas (I) to (XVIII), (XXV) to (XXVII), In certain embodiments of any of (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R1 may be selected from H, Cl, F, Me, —CF, —OMe, —CN, —C(O)NMe, alkyl, propyl, isopropyl, and cyclopropyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3R)-azetidin-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (S)-but-4-yl-1,3-diol. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is -N(Me)-.

[0173] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -NHCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is —C(O)—; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -CH2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(H)=; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -SO2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 is -NHCH2-; L 2 is -NH-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -N(Me)-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(H)=;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -SO2-;L 3 is CH2-; and R 2 and R 3and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), L 1 is -NHCH2-; L 2 is -NH-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -N(Me)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(H)=;L 3 is -CH2-; R2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; and L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; and L 2 is -C(O)-; L 3 is -CH2-; R2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -NHCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazol-5-yl. Formulas (I) to (XVIII), (XXV In certain embodiments of any of (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R1 may be selected from H, Cl, F, Me, —CF, —OMe, —CN, —C(O)NMe, alkyl, propyl, isopropyl, and cyclopropyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3R)-azetidin-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), R 4 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is -N(Me)-.

[0174] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 is -N(Me)CH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), L 1 is -N(Me)CH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is —C(O)—; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -CH2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(H)=; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -SO2-; and L 3In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -NH-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -N(Me)-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(H)=;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 is -N(Me)CH2-; L 2 is -SO2-;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -NH-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -N(Me)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -N(Me)CH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl. Any of the compounds of formula (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII) In any particular embodiment, L 1 is -N(Me)CH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -N(Me)-; L 3 is -CH2-; R2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -N(Me)CH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -N(Me)CH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R 1 may be selected from H, Cl, F, Me, —CF, —OMe, —CN, —C(O)NMe, alkyl, propyl, isopropyl, and cyclopropyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3R)-azetidin-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is -N(Me)-.

[0175] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 is -OC(H,Me)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-, and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is —C(O)—; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2is -CH2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(H)=; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -SO2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -NH-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), L 1 is -OC(H,Me)-; L 2 is -N(Me)-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(O)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -CH2-; L 3is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(H)=;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -SO2-;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -NH-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -N(Me)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(O)-; L 3 is -CH2-; R2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -NH-; L 3 is -CH2-; R 2and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R 1 may be selected from H, Cl, F, Me, —CF, —OMe, —CN, —C(O)NMe, alkyl, propyl, isopropyl, and cyclopropyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is (3R)-azetidin-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (S)-but-4-yl-1,3-diol. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is -N(Me)-.

[0176] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 , -SO2NH-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -SO2NH-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; and L 2 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is —C(O)—; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -CH2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XVII), L 1 is -SO2NH-; L 2 is -C(H)=; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -SO2-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -NH-; and L 3In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -N(Me)-; and L 3 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(O)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -CH2-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(H)=;L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -SO2-;L 3 is -CH2-; and R 2 and R 3and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -NH-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -N(Me)-; L 3 is -CH2-; and R 2 and R 3 and each is H. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XVII), L 1 is -SO2NH-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(H)=;L 3is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -N(Me)-; L 3 teeth,- CH2-;R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(O)-; L 3 is -CH2-; R 2and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIVII), L 1 is -SO2NH-; L2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), L 1 is -SO2NH-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (2S)-oxetan-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazol-5-yl. Formulas (I) to (XVIII), (XXV) to (XXVII), In certain embodiments of any of (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R1 may be selected from H, Cl, F, Me, —CF, —OMe, —CN, —C(O)NMe, alkyl, propyl, isopropyl, and cyclopropyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3R)-azetidin-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), and (XXXI), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is -N(Me)-.

[0177] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -O-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazol-5-yl. Formulas (I) to (XVIII), (XXV) to (XX In certain embodiments of any of VII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R 1 may be selected from H, Cl, F, Me, —CF, —OMe, —CN, —C(O)NMe, alkyl, propyl, isopropyl, and cyclopropyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (3R)-azetidin-3-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-hydroxyl-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (1-methyl-1H-imidazol-5-yl)-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl}. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidin-2-yl]methyl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 In certain embodiments, there is provided a compound of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2 is -N(Me)-.

[0178] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; R 2and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is —COOH. Formulas (I) to (XVIII), (XXV) to (XXVII), (XX In certain embodiments of any of (X), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In any embodiment according to this paragraph, R 1 may be selected from H, Cl, F, Me, —CF 3 , —OMe, —CN, —C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl.

[0179] In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are each H; and R 4In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are each H; and R 4 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -OCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -OCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is —COOH. Formulas (I) to (XVIII), (XXV) to (XXVII), (XX In certain embodiments of any of (X), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -CH2-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(H)=;L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -SO2-;L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -NH-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -N(Me)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is oxelan-3-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tetrazol-5-yl. In certain embodiments of any of Formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-; L 2 is -C(O)-; L 3 is -CH2-; R 2 and R 3 are H; R 4 is 1,3-oxazol-2-yl-methyl; and R 5 is tetrazolyl, e.g., 1H-1,2,3,4-tet...

Claims

1. A compound of formula I, or a pharma- ceutically acceptable salt, or stereoisomer thereof: 【Chemistry 1】 In the formula, A is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted cycloalkyl, -NMe ２ , or -CF ３ and Ring B is a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubstituted bicyclic; Ring C is a substituted or unsubstituted heterocycloalkyl or a substituted or unsubstituted heterocycloalkenyl, each of which is represented by L as shown. ３ at least one N bonded to D １ , D ２ , and D ３ 0, 1, or 2 of the groups are N, and the rest are CH or CR ６ and W is N, CR １４ or C; W is CR １４ when W is C, the adjacent dashed line represents a double bond, or when L ２ is -C(H)=; L １ is a bond, —O—, —CH ２ -, -NH-, -N(Me)-, -N(Et)-, -OCH ２ -, -OC(H,Me)-, -CH ２ O-, -NHCH ２ -, -N(Me)CH ２ - and -SO ２ NH-; L ２ is a bond, -C(O)-, -CH ２ -, -C(H)=, -SO ２ -, -O-, -CF ２ -, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and 【Chemistry 2】 selected from the group consisting of: L ３ is -CH ２ - or -C(O)-; L ４ does not exist or L ４ L １ and together with rings A and B form a fused tricyclic ring, and L ５ does not exist; L ５ does not exist or L ５ L ２ and together with rings B and C form a fused tricyclic ring; L ４ does not exist; R ４ is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R ５ は、-COOH、-COCF ３ 、-C(OH)CF ３ 、-CONHCN、-CONHOH、CONHOMe、-CONHSO ２ N(Me) ２ 、-PO ３ H ２ 、-PO(Me)(OH)、-SO ３ 2019-02-20 ２ NH ２ 、-SO ２ NHMe、-B(OH) ２ 、 【Chemistry 3】 and tetrazolyl; Each R ６ is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R １１ R １２ NCO- and R １１ R １２ N-; R １１ is hydrogen or alkyl; R １２ is hydrogen or alkyl; R １３ is hydrogen or alkyl; R １４ is hydrogen, cyano, halo, hydroxyl, alkyl, haloalkyl, methyl, CH ２ F, or CH ２ OH; In the ceremony, L １ Ga-CH ２ O- and L ４ does not exist and L ５ If does not exist, then L ２ is -C(O)-, -CH ２ -, -C(H)=, -SO ２ -, -O-, or 【Chemistry 4】 or L ３ is --C(O)--, or both, or a pharma- ceutically acceptable salt, or stereoisomer thereof.

2. A compound of formula XXX, or a pharma- ceutically acceptable salt, or stereoisomer thereof: 【Chemistry 5】 where W is N, CH, or C; when W is CH, the adjacent dashed line represents a single bond; when W is C, the adjacent dashed line represents a double bond; A １ , A ２ , A ３ , A ４ , and A ５ 0, 1, or 2 of the aryl groups are N, and the rest are CH or CR. １ and B １ , B ２ , B ３ , and B ４ 0, 1, or 2 of the groups are N, and the rest are CH or CR ２ and D １ , D ２ , and D ３ 0, 1, or 2 of the groups are N, and the rest are CH or CR ６ and L １ is -O-, -CH ２ -, -NH-, -N(Me)-, -N(Et)-, -OCH ２ --, --CH ２ O-, -NHCH ２ -, -N(Me)CH ２ - and -SO ２ NH-; L ２ is a bond, -C(O)-, -CH ２ -, -C(H)=, -SO ２ -, -O-, -CF ２ -, -CHF-, -CH(OH)-, NH-, -N(Me)-, and 【Chemistry 6】 selected from the group consisting of: L ３ is -CH ２ - or -C(O)-; Each R １ are independently selected from alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R １１ R １２ NCO-; Each R ２ is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R １１ R １２ NCO-; Each R ３ is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R １１ R １２ NCO-; R ４ is unsubstituted alkyl, substituted alkyl, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R ５ は、-COOH、-COCF ３ 、-C(OH)CF ３ 、-CONHCN、-CONHOH、CONHOMe、-CONHSO ２ N(Me) ２ 、-PO ３ H ２ 、-PO(Me)(OH)、-SO ３ 2019-02-20 ２ NH ２ 、-SO ２ NHMe、-B(OH) ２ 、 【Chemistry 7】 and tetrazolyl; Each R ６ is alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, R １１ R １２ NCO- and R １１ R １２ N-; R １１ is hydrogen or alkyl; R １２ is hydrogen or alkyl; R １３ is hydrogen or alkyl; and The compound, or a pharma- ceutically acceptable salt, or stereoisomer thereof, wherein o is an integer from 0 to 4.

3. 1. A compound of formula XXXI, or a pharma- ceutically acceptable salt, or stereoisomer thereof: 【Chemistry 8】 Wherein W is N, CH, or C; when W is CH, the adjacent dashed line indicates a unit; １ , A ２ , A ３ , A ４ , and A ５ 0, 1, or 2 of the groups are N, and the rest are CH or CR １ and D １ , D ２ , and D ３ 0, 1, or 2 of the groups are N, and the rest are CH or CR ６ and Each R １ is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R １１ R １２ NCO-; L １ is -O-, -CH ２ -, -NH-, -N(Me)-, -N(Et)-, -OCH ２ --, --CH ２ O-, -NHCH ２ -, -N(Me)CH ２ - and -SO ２ NH-; L ２ is a bond, -C(O)-, -CH ２ -, -C(H)=, -SO ２ -, -O-, -CF ２ -, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and 【Chemistry 9】 selected from the group consisting of: L ３ is -C ２ -, or -C(O)-; Each R ３ is alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R １１ R １２ NCO-; R ４ is unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R ５ は、-COOH、-COCF ３ 、-C(OH)CF ３ 、-CONHCN、-CONHOH、CONHOMe、-CONHSO ２ N(Me) ２ 、-PO ３ H ２ 、-PO(Me)(OH)、-SO ３ 2019-02-20 ２ NH ２ 、-SO ２ NHMe、-B(OH) ２ 、 【Chemistry 10】 and tetrazolyl; Each R ６ is independently selected from the group consisting of F and methyl; R １１ is hydrogen or alkyl; R １２ is hydrogen or alkyl; R １３ is hydrogen, or alkyl; and The compound, or a pharma- ceutically acceptable salt, or stereoisomer thereof, wherein o is 1, 2, 3, or 4.

4. L ２ But -CH ２ -, -C(O)-, or -SO ２ The compound according to any one of claims 1 to 3, wherein

5. L ２ The compound according to any one of claims 1 to 3, wherein is -CH= or -O-.

6. L ２ But -CF ２ The compound according to any one of claims 1 to 3, wherein the aryl group is -, -CHF-, or -CHOH-.

7. L ２ Ga-CH ２ The compound according to any one of claims 1 to 3, wherein

8. L ２ The compound according to any one of claims 1 to 3, wherein is -NH- or -N(Me)-.

9. L ２ The compound of formula XXX according to claim 2, wherein is a bond.

10. L １ But -CH ２ O- or -OCH ２ 3. The compound of formula XXX according to claim 2, wherein

11. A compound selected from the following, or a pharma- ceutically acceptable salt or solvate thereof: 【Table 1-1】 【Table 1-2】 【Table 1-3】 【Table 1-4】 【Table 1-5】 【Table 1-6】 【Table 1-7】 【Table 1-8】 【Table 1-9】 【Table 1-10】 【Table 1-11】 【Table 1-12】 【Table 1-13】 【Table 1-14】 【Table 1-15】 【Table 1-16】 【Table 1-17】 【Table 1-18】 【Table 1-19】 【Table 1-20】 【Table 1-21】 【Table 1-22】 【Table 1-23】 【Table 1-24】 【Table 1-25】 【Table 1-26】 【Table 1-27】 【Table 1-28】 【Table 1-29】 【Table 1-30】 【Table 1-31】 【Table 1-32】 【Table 1-33】 【Table 1-34】 【Table 1-35】 【Table 1-36】 【Table 1-37】 【Table 1-38】 【Table 1-39】 【Table 1-40】 【Table 1-41】 【Table 1-42】 【Table 1-43】 【Table 1-44】 【Table 1-45】 【Table 1-46】 【Table 1-47】 【Table 1-48】 【Table 1-49】 【Table 1-50】 【Table 1-51】 【Table 1-52】 【Table 1-53】 【Table 1-54】 【Table 1-55】 【Table 1-56】 【Table 1-57】 【Table 1-58】 【Table 1-59】 【Table 1-60】 【Table 1-61】 【Table 1-62】 【Table 1-63】 【Table 1-64】 【Table 1-65】 【Table 1-66】 【Table 1-67】 【Table 1-68】 【Table 1-69】 【Table 1-70】 【Table 1-71】 【Table 1-72】 【Table 1-73】 【Table 1-74】 【Table 1-75】 【Table 1-76】 【Table 1-77】 【Table 1-78】 【Table 1-79】 【Table 1-80】 【Table 1-81】 【Table 1-82】 【Table 1-83】 【Table 1-84】

12. A pharmaceutical composition comprising a compound according to any one of claims 1 to 11, or a pharma- ceutically acceptable salt thereof, and one or more pharma- ceutically acceptable carriers, excipients or diluents.

13. A compound according to any one of claims 1 to 11 or a pharmaceutical composition according to claim 12 for use in therapy.

14. A compound according to any one of claims 1 to 11, or a pharmaceutical composition according to claim 12, for use in the treatment of a metabolic disease or disorder.

15. Use of a compound according to any one of claims 1 to 11, or a pharmaceutical composition according to claim 12, in the manufacture of a medicament for the treatment of a metabolic disease or disorder.

Images