GPCR receptor antagonists, pharmaceutical compositions thereof and methods for their use
Patent Information
- Application Number
- DE602022043224
- Authority / Receiving Office
- DE · DE
- Patent Type
- Patents
- Current Assignee / Owner
- Priority Date
- 2021-11-02
- Filing Date
- 2022-01-27
- Publication Date
- 2026-09-16
- Estimated Expiration
- 2042-01-27
AI Technical Summary
Diabetes is a serious chronic disease that occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces.
Description
[0001] Provided herein are GLP-1 receptor modulator compounds; pharmaceutical compositions comprising the compounds; and the compounds, and compositions for use in therapy, including the treatment of type 2 diabetes. The compounds, and compositions are useful, for instance, in methods of treatment, and prevention of metabolic diseases or conditions, methods of detection of metabolic diseases or conditions, and methods of diagnosis of metabolic diseases or conditions.BACKGROUND
[0002] Diabetes is a serious chronic disease that occurs when the pancreas does not produce enough insulin, or when the body cannot effectively use the insulin it produces. Complications of diabetes include, damage to the heart, blood vessels, eyes, kidneys, and nerves. Diabetes can increase risk of heart disease, and stroke. The results include serious effects on quality of life, health, and mortality. WHO Global Report on Diabetes, 2016, World Health Organization. As of 2017, approximately 462 million individuals worldwide, about 6.28% of the population was affected by type 2 diabetes, and this prevalence was increasing measurably. Khan et al., 2020, J. Epidemiol. Glob. Health 10(1):107-111. The global economic burden of diabetes in 2015 was estimated to be $1.3T, and estimated to increase to $2.1T 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.
[0003] 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) enhances 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 weight in humans. Shah and Vella, 2014 Rev Endocr Metab Disord. 15(3): 181-187. Activating the GLP-1 receptor has been shown to have beneficial effects on insulin secretion and the maintenance of beta cell glucose sensing, transcription, synthesis, proliferation, and survival. Doyle and Egan, 2007, supra. While 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.
[0004] US 2018 / 0170908 A1 discloses 6-carboxylic acids of benzimidazoles and 4-aza-, 5-aza-, 7-aza- and 4,7-diaza-benzimidazoles as GLP-1R agonists, processes to make said compounds, and methods comprising administering said compounds to a mammal in need thereof.
[0005] WO 2020 / 103815 A1 discloses compounds and pharmaceutical compositions thereof which are said to be useful in e.g. treating type 2 diabetes mellitus, pre-diabetes, obesity, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and cardiovascular disease.
[0006] US 2019 / 0382384 A1 discloses 6-carboxylic acids of benzimidazoles and 4-aza-, 5-aza-, and 7-aza-benzimidazoles as GLP-1R agonists, processes to make said compounds, and methods comprising administering said compounds to a mammal in need thereof.
[0007] There is a need for additional therapies for treating metabolic diseases, and conditions, like type 2 diabetes. Small molecules targeting GLP-1 receptor should provide safe, stable, and easy to administer therapeutics for metabolic diseases, and conditions such as type 2 diabetes.SUMMARY OF THE INVENTION
[0008] In one aspect, the claimed invention provides a compound which is 2-{[(2S,4S)-4-({2-[(2,4-difluorophenoxy)methyl]pyrimidin-4-yl}oxy)-2-methylpiperidin-1-yl]methyl}-1-{[(2S)-oxetan-2-yl]methyl}-1H-1,3-benzodiazole-6-carboxylic acid: or a pharmaceutically acceptable salt or solvate thereof. In a further aspect, the invention provides a pharmaceutical composition comprising the compound of the invention and one or more pharmaceutically acceptable carriers, excipients, or diluents. In a further aspect, the invention provides the compound or the composition of the invention for use in therapy. In a further aspect, the invention provides the compound or the composition of the invention for use in the treatment of type 2 diabetes.SUMMARY OF THE DISCLOSURE
[0009] Provided herein are GLP-1 receptor modulator compounds of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL -XLVII ), and sub-formulas thereof, compositions comprising the compounds, methods of producing the compounds, and methods of using the compounds, and compositions in treatment, and diagnosis. The compounds of Formula (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), and sub-formulas and instances thereof, are useful for modulating the activity of GLP-1 receptor. In certain instances, the compounds can be used to agonize the activity of GLP-1 receptor. In certain instances, the compounds can be used for treating diseases, or conditions modulated by GLP-1 receptor.
[0010] In one aspect, provided is a compound of Formula (I ), or a pharmaceutically acceptable salt, or stereoisomer thereof: wherein, A is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, -NMe 2 , or -CF 3 ; Ring B is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or substituted or unsubsuted bicyclic; Ring C is substituted or unsubstituted heterocycloalkyl, or substituted or unsubstituted heterocycloalkenyl, each comprising at least one N, linked to L 3< as depicted; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of 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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -CF 2 -. -CHF-, -CH(OH)-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; L 4< is absent, or L 4< together with L 1< and Rings A and B form a fused tricycle, and L 5< is absent; L 5< is absent, or L 5< together with L 2< and Rings B and C form a fused tricycle, and L 4< is absent; 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, - CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , - SO 2 NHMe, -B(OH) 2 , and tetrazolyl; each R 6< is independently selected from the group consisting of 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, haloalklyl, methyl, CH 2 F, or CH 2 OH; wherein when L 1< is a -CH 2 O-, L 4< is absent, and L 5< is absent, then either L 2< is -C(O)-, -CH 2 -, - C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, or or L 3< is -C(O)-, or both.
[0011] In one aspect, provided is a compound of Formula (Ia), or a pharmaceutically acceptable salt, or stereoisomer thereof: wherein, A is substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, -NMe 2 , or -CF 3 ; Ring B is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Ring C is further unsubstituted or further substituted, and / or bridged; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH or CR 6< ; W is N, CH, or C; when W is CH the adjacent dashed lines indicate single bonds; when W is C, one adjacent dashed line indicates a double bond, for instance L 2< is - C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -CF 2 -, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; L 4< is absent, or L 4< together with L 1< and Rings A and B form a fused tricycle, and L 5< is absent; L 5< is absent, or L 5< together with L 2< and Rings B and C form a fused tricycle, and L 4< is absent; 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, - CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , - SO 2 NHMe, -B(OH) 2 , and tetrazolyl; each R 6< is independently selected from the group consisting of 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; and R 13< is hydrogen or alkyl; wherein, when L 1< is -CH 2 O-, L 4< is absent, and L 5< is absent, then either L 2< is -C(O)-, -CH 2 -, - C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, or or L 3< is -C(O)-, or both.
[0012] In one aspect, provided is a compound of Formula (XXX), or a pharmaceutically acceptable salt, or stereoisomer thereof: Wherein, W is N, CH, or C; when W is CH, the adjacent dashed lines indicate single bonds; when W is C, one adjacent dashed line indicates a double bond, for instance L 2< is -C(H)=; zero, one, or two of A 1< , A 2< , A 3< , A 4< , and A 5< are N, and the rest are CH or CR 1< ; zero, one, or two of B 1< , B 2< , B 3< , and B 4< are N, and the rest are CH or CR 2< ; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH or CR 6< ; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -. -C(H)=, -SO 2 -, -O-, -CF 2 -, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, - CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , - SO 2 NHMe, -B(OH) 2 , and tetrazolyl; each R 6< is independently selected from the group consisting of 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 o is an integer from 0 to 4.
[0013] In one aspect provided herein is a compound of Formula XXXI, or a pharmaceutically acceptable salt, or stereoisomer thereof: wherein W is N, CH, or C; when W is CH, the adjacent dashed lines indicate single; zero, one, or two of A 1< , A 2< , A 3< , A 4< , and A 5< are N, and the rest are CH, or CR 1< ; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -. -C(H)=, -SO 2 -, -O-, -CF 2 -, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 3< is independently selected from the group consisting of 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, - CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , - SO 2 NHMe, -B(OH) 2 , 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.
[0014] In certain aspects, the compounds are useful in methods of treatment and prevention of metabolic diseases, and conditions, methods of detection of metabolic diseases, and conditions, and methods of diagnosis of metabolic diseases, and conditions. Throughout this disclosure, references to methods of treatment by therapy and methods of diagnosis are to be interpreted as references to compounds and pharmaceutical compositions of the present disclosure for use in those methods of treatment and methods of diagnosis.
[0015] In another aspect, provided are compositions comprising a compound of Formula (I ), (Ia ), (XXX ), or (XXXI ). In some instances, the compositions are pharmaceutical compositions. Any suitable pharmaceutical composition may be used. In a further aspect, provided herein is a kit comprising the compound of Formula (I ), (Ia ), (XXX ), or (XXXI ), or instances thereof, or a pharmaceutical composition thereof.
[0016] In another aspect, provided herein are methods of using the compounds or the compositions described herein. In some instances, the methods are for treatment. In some instances, the methods are diagnostic methods. In some instances, the methods are analytical methods. In some instances, 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 instances, the disease is type 2 diabetes.
[0017] Also provided herein is the use of compounds described herein, and compositions thereof, for the treatment of a metabolic disease, or condition. Also provided herein is the use of compounds described herein, and compositions thereof, for the treatment of type 2 diabetes.BRIEF DESCRIPTION OF THE FIGURES
[0018] FIG. 1 provides intravenous glucose tolerance test (IVGTT) in cynomolgus monkeys.DESCRIPTION OF EXEMPLARY INSTANCES
[0019] Described herein are GLP-1 receptor compounds useful for treating metabolic diseases or conditions, such as type 2 diabetes.Definitions
[0020] Unless otherwise defined, all terms of art, notations and other scientific terminology used herein are intended to have the meanings commonly understood by those of skill in the art to which this disclosure pertains. In some cases, terms with commonly understood meanings are defined herein for clarity, and / or ready reference. The techniques and procedures described or referenced herein are generally well understood, and are commonly employed using conventional methodologies by those skilled in the art. As appropriate, procedures involving the use of commercially available kits, and reagents are generally carried out in accordance with manufacturer-defined protocols, and conditions unless otherwise noted.
[0021] As used herein, the singular forms "a," "an," and "the" include the plural referents unless the context clearly indicates otherwise.
[0022] The term "about" indicates and encompasses an indicated value, and a range above and below that value. In certain instances, the term "about" indicates the designated value ± 10%, ± 5%, or ± 1%. In certain instances, the term "about" indicates the designated value ± one standard deviation of that value. In certain instances, for example, logarithmic scales (e.g., pH), the term "about" indicates the designated value ± 0.3, ± 0.2, or ± 0.1.
[0023] When referring to the compounds provided herein, the following terms have the following meanings unless indicated otherwise. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art. In the event that there is a plurality of definitions for a term herein, those in this section prevail unless stated otherwise.
[0024] "Alkoxy" and "alkoxyl," refer to the group -OR" where R" is alkyl or cycloalkyl. Alkoxy groups include, in certain instances, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, 1,2-dimethylbutoxy, and the like.
[0025] The term "alkoxyamine," as used herein, refers to the group -alkylene-O-NH 2 , wherein alkylene is as defined herein. In some instances, alkoxyamine groups can react with aldehydes to form oxime residues. Examples of alkoxyamine groups include -CH 2 CH 2 -O-NH 2 and -CH 2 -O-NH 2 .
[0026] The term "alkyl," as used herein, unless otherwise specified, refers to a saturated straight, or branched hydrocarbon. In certain instances, the alkyl group is a primary, secondary, or tertiary hydrocarbon. In certain instances, the alkyl group includes one to ten carbon atoms (i.e., C 1 to C 10 alkyl). In certain instances, the alkyl is a lower alkyl, for example, C 1-6 alkyl, and the like. In certain instances, 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 instances, "substituted alkyl" refers to an alkyl substituted with one, two, or three groups independently selected from a 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 instances, alkyl is unsubstituted.
[0027] 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 instances, alkylene is unsubstituted.
[0028] "Alkenyl" refers to an olefinically unsaturated hydrocarbon group, in certain instances, having up to about eleven carbon atoms, or from two to six carbon atoms (e.g., "lower alkenyl"), which can be straight-chained or branched, and having at least one, or from one to two sites of olefinic unsaturation. "Substituted alkenyl" refers to an alkenyl group substituted as described herein for alkyl.
[0029] "Alkenylene" refers to a divalent alkenyl as defined herein. Lower alkenylene is, for example, C 2 -C 6 -alkenylene.
[0030] "Alkynyl" refers to acetylenically unsaturated hydrocarbon groups, in certain instances, having up to about eleven carbon atoms, or from two to six carbon atoms (e.g., "lower alkynyl"), which can be straight-chained or branched, and having at least one, or from one to two sites of acetylenic unsaturation. Non-limiting examples of alkynyl groups include acetylene (-C≡CH), propargyl (-CH 2 C≡CH), and the like. "Substituted alkynyl" refers to an alkynyl group substituted as described herein for alkyl.
[0031] "Alkynylene" refers to a divalent alkynyl as defined herein. Lower alkynylene is, for example, C 2 -C 6 -alkynylene.
[0032] "Amino" refers to -NH 2 .
[0033] The term "alkylamino," as used herein, and unless otherwise specified, refers to the group -NHR" where R" is, for example, C 1-10 alkyl, as defined herein. In certain instances, alkylamino is C 1-6 alkylamino.
[0034] The term "dialkylamino," as used herein, and unless otherwise specified, refers to the group -NR"R" where, each R" is independently C 1-10 alkyl, as defined herein. In certain instances, dialkylamino is di-C 1-6 alkylamino.
[0035] The term "aryl," as used herein, and unless otherwise specified, refers to phenyl, biphenyl, or naphthyl. The term includes both substituted and unsubstituted moieties. An aryl group can be substituted with any described moiety including, but not limited to, one or more moieties (e.g., in some instances 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, wherein each moiety is independently either unprotected, or protected as necessary, as would be appreciated by those skilled in the art (e.g., Greene, et al., Protective Groups in Organic Synthesis, John Wiley and Sons, Second Edition, 1991); and wherein the aryl in the arylamino and aryloxy substituents are not further substituted.
[0036] The term "arylamino," as used herein, and unless otherwise specified, refers to an -NR'R" group where R' is hydrogen, or C 1 -C 6 -alkyl; and R" is aryl, as defined herein.
[0037] The term "arylene," as used herein, and unless otherwise specified, refers to a divalent aryl group, as defined herein.
[0038] The term "aryloxy," as used herein, and unless otherwise specified, refers to an -OR group where R is aryl, as defined herein.
[0039] "Alkarylene" refers to an arylene group, as defined herein, wherein the aryl ring is substituted with one or two alkyl groups. "Substituted alkarylene" refers to an alkarylene, as defined herein, where the arylene group is further substituted, as defined herein for aryl.
[0040] "Aralkylene" refers to an -alkyl-arylene- or arylene-alkyl, for instance, a -C 1 -C 2 alkyl-arylene-, -arylene-C 1 -C 2 alkyl-, or - C 1 -C 2 alkyl-arylene-C 1 -C 2 alkyl- group, where arylene is as defined herein. "Substituted aralkylene" refers to an aralkylene, as defined herein, where the aralkylene group is substituted, as defined herein for aryl. "Substituted C 1 -C 2 alkyl" refers to a C 1 -C 2 alkyl group that is substituted as defined herein for an alkyl.
[0041] "Arylalkylene" refers to -alkyl-arylene- or arylene-alkyl, for instance, a -C 1 -C 2 alkyl-arylene-, -arylene-C 1 -C 2 alkyl -, or - C 1 -C 2 alkyl-arylene-C 1 -C 2 alkyl- group, where arylene is as defined herein. "Substituted arylalkylene" refers to an arylalkylene, as defined herein, where the arylalkylene group is substituted, as defined herein for aryl. "Substituted C 1 -C 2 alkyl" refers to a C 1 -C 2 alkyl group that is substituted as defined herein for an alkyl.
[0042] "Carboxyl" or "carboxy" refers to -C(O)OH or -COOH.
[0043] The term "cycloalkyl," as used herein, unless otherwise specified, refers to a saturated cyclic hydrocarbon. In certain instances, the cycloalkyl group may be a saturated, and / or bridged, and / or non-bridged, and / or a fused bicyclic group. In certain instances, the cycloalkyl group includes three to ten carbon atoms (i.e., C 3 to C 10 cycloalkyl). In some instances, the cycloalkyl has from three to fifteen carbons (C 3-15 ), from three to ten carbons (C 3-10 ), from three to seven carbons (C 3-7 ), or from three to six carbons (C 3 -C 6 ) (i.e., "lower cycloalkyl"). In certain instances, the cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexylmethyl, cycloheptyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, decalinyl, or adamantyl.
[0044] The term "cycloalkylene," as used herein refers to a divalent cycloalkyl group, as defined herein. In certain instances, the cycloalkylene group is cyclopropylene cyclobutylene , cyclopentylene cyclohexylene cycloheptylene and the like. Lower cycloalkylene refers to a C 3 -C 6 -cycloalkylene.
[0045] The term "cycloalkylalkyl," as used herein, unless otherwise specified, refers to an alkyl group, as defined herein, substituted with one or two cycloalkyl, as defined herein.
[0046] The term "ester," as used herein, refers to -C(O)OR , or -COOR , where R is alkyl, as defined herein.
[0047] The term "haloalkyl" refers to an alkyl group, as defined herein, substituted with one, or more halogen atoms (e.g., in some instances one, two, three, four, or five) which are independently selected.
[0048] The term "heteroalkyl" refers to an alkyl, as defined herein, in which one or more carbon atoms are replaced by heteroatoms. As used herein, "heteroalkenyl" refers to an alkenyl, as defined herein, in which one, or more carbon atoms are replaced by heteroatoms. As used herein, "heteroalkynyl" refers to an alkynyl, as defined herein, in which one, or more carbon atoms are replaced by heteroatoms. 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 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 instances, a heteroalkyl group may comprise one, two, three, or four heteroatoms. Those of skill in the art will recognize that a 4-membered heteroalkyl may generally comprise one, or two heteroatoms, a 5- or 6-membered heteroalkyl may generally comprise one, two, or three heteroatoms, and a 7- to 10-membered heteroalkyl may generally comprise one, two, three, or four heteroatoms.
[0049] The term "heteroalkylene," as used herein, refers to a divalent heteroalkyl, as defined herein. "Substituted heteroalkylene" refers to a divalent heteroalkyl, as defined herein, substituted as described for heteroalkyl.
[0050] The term "heterocycloalkyl" refers to a monovalent, monocyclic, or multicyclic non-aromatic ring system, wherein one, or more of the ring atoms are heteroatoms independently selected from oxygen (O), sulfur (S), and nitrogen (N) (e.g., where the nitrogen, or sulfur atoms may be optionally oxidized, and the nitrogen atoms may be optionally quaternized) and the remaining ring atoms of the non-aromatic ring are carbon atoms. In certain instances, heterocycloalkyl is a monovalent, monocyclic, or multicyclic fully-saturated ring system. In certain instances, the heterocycloalkyl group has from three to twenty, from three to fifteen, from three to ten, from three to eight, from four to seven, from four to eleven, or from five to six ring atoms. The heterocycloalkyl may be attached to a core structure at any heteroatom or carbon atom which results in the creation of a stable compound. In certain instances, the heterocycloalkyl is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, which may include a fused or bridged ring system and in which the nitrogen or sulfur atoms may be optionally oxidized, and / or the nitrogen atoms may be optionally quaternized. In some instances, 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, isothiazolidinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, oxazolidinonyl, oxazolidinyl, oxiranyl, piperazinyl, piperidinyl, 4-piperidonyl, pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolinyl, quinuclidinyl, tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydrothienyl, thiamorpholinyl, thiazolidinyl, tetrahydroquinolinyl, and 1,3,5-trithianyl. In certain instances, heterocycloalkyl may also be optionally substituted as described herein. In certain instances, 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 instances, a heterocycloalkyl group may comprise one, two, three, or four heteroatoms. Those of skill in the art will recognize that a 4-membered heterocycloalkyl may generally comprise one or two heteroatoms, a 5 or 6-membered heterocycloalkyl may generally comprise one, two, or three heteroatoms, and a 7-to 10-membered heterocycloalkyl may generally comprise one, two, three, or four heteroatoms.
[0051] "Heterocycloalkylene" refers to a divalent heterocycloalkyl as defined herein.
[0052] The term "heteroaryl" refers to a monovalent monocyclic aromatic group, and / or multicyclic aromatic group, wherein at least one aromatic ring contains one, or more heteroatoms independently selected from oxygen, sulfur, and nitrogen in the ring. Each ring of a heteroaryl group can 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 instances, the heteroaryl has from five to twenty, from five to fifteen, or from five to ten ring atoms. A heteroaryl may be attached to the rest of the molecule via a nitrogen or a carbon atom. In some instances, 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, benzoisoxazolyl, 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 instances, heteroaryl may also be optionally substituted as described herein. "Substituted heteroaryl" is a heteroaryl substituted as defined for aryl.
[0053] The term "heteroarylene" refers to a divalent heteroaryl group, as defined herein. "Substituted heteroarylene" is a heteroarylene substituted as defined for aryl.
[0054] The term "heteroarylalkylene" refers to -alkyl-heteroarylene- or -heteroarylene-alkyl, for instance, a a -C 1 -C 2 alkyl-heteroarylene-, -heteroarylene-C 1 -C 2 alkyl-, or -C 1 -C 2 alkyl-heteroarylene-C 1 -C 2 alkyl- group, where heteroarylene is as defined herein. "Substituted heteroarylalkylene" refers to a heteroarylalkylene, as defined herein, where the heteroarylalkylene group is substituted, as defined herein for aryl. "Substituted C 1 -C 2 alkyl" refers to a C 1 -C 2 alkyl group that is substituted as defined herein for an alkyl.
[0055] As used herein, an "oxo" refers to =O.
[0056] The term "protecting group," as used herein, and unless otherwise specified, refers to a group that is added to an oxygen, nitrogen, or phosphorus atom to prevent its further reaction, 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, e.g., Greene, et al., Protective Groups in Organic Synthesis, John Wiley and Sons, Fourth Edition, 2006).
[0057] "Pharmaceutically acceptable salt" refers to any salt of a compound provided herein which retains its biological properties, and which is not toxic or otherwise undesirable for pharmaceutical use. Such salts may be derived from a variety of organic, and inorganic counter-ions well known in the art. Such salts include, but are not limited to (1) acid addition salts formed with organic, or inorganic acids such as hydrochloric, hydrobromic, sulfuric, nitric, phosphoric, sulfamic, acetic, trifluoroacetic, trichloroacetic, propionic, hexanoic, cyclopentylpropionic, glycolic, glutaric, pyruvic, lactic, malonic, succinic, sorbic, ascorbic, malic, maleic, fumaric, tartaric, citric, benzoic, 3-(4-hydroxybenzoyl)benzoic, picric, cinnamic, mandelic, phthalic, lauric, methanesulfonic, ethanesulfonic, 1,2-ethane-disulfonic, 2-hydroxyethanesulfonic, benzenesulfonic, 4-chlorobenzenesulfonic, 2-naphthalenesulfonic, 4-toluenesulfonic, camphoric, camphorsulfonic, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylic, glucoheptonic, 3-phenylpropionic, trimethylacetic, tert-butylacetic, lauryl sulfuric, gluconic, glutamic, hydroxynaphthoic, salicylic, stearic, cyclohexylsulfamic, quinic, muconic acid, and the like; or (2) salts formed when an acidic proton present in the parent compound either (a) is replaced by a metal ion, for example, an alkali metal ion, an alkaline earth ion, or an aluminum ion, or alkali metal, or alkaline earth metal hydroxides, such as sodium, potassium, calcium, magnesium, aluminum, lithium, zinc, and barium hydroxide, or ammonia; or (b) coordinates with an organic base, such as aliphatic, alicyclic, or aromatic organic amines, including, without limitation, 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.
[0058] Pharmaceutically acceptable salts further include, by way of example and without limitation, sodium, potassium, calcium, magnesium, ammonium, and tetraalkylammonium salts, and the like, and when the compound contains a basic functionality, salts of non-toxic organic, or inorganic acids, such as hydrohalides, for example, hydrochloride and hydrobromide, sulfate, phosphate, sulfamate, nitrate, acetate, trifluoroacetate, trichloroacetate, propionate, hexanoate, cyclopentylpropionate, glycolate, glutarate, pyruvate, lactate, malonate, succinate, sorbate, ascorbate, malate, maleate, fumarate, tartarate, citrate, benzoate, 3-(4-hydroxybenzoyl)benzoate, picrate, cinnamate, mandelate, phthalate, laurate, methanesulfonate (mesylate), ethanesulfonate, 1,2-ethane-disulfonate, 2-hydroxyethanesulfonate, benzenesulfonate (besylate), 4-chlorobenzenesulfonate, 2-naphthalenesulfonate, 4-toluenesulfonate, camphorate, camphorsulfonate, 4-methylbicyclo[2.2.2]-oct-2-ene-1-carboxylate, glucoheptonate, 3-phenylpropionate, trimethylacetate, tert-butylacetate, lauryl sulfate, gluconate, glutamate, hydroxynaphthoate, salicylate, stearate, cyclohexylsulfamate, quinate, muconate, and the like.
[0059] The term "substantially free of" or "substantially in the absence of" with respect to a composition refers to a composition that includes at least 85%, or 90% by weight, in certain instances 95%, 98 %, 99%, or 100% by weight; or in certain instances, 95%, 98%, 99%, or 100% of the designated enantiomer or diastereomer of a compound. In certain instances, in the methods and compounds provided herein, the compounds are substantially free of one of two enantiomers. In certain instances, in the methods and compounds provided herein, the compounds are substantially free of one of two diastereomers. In certain instances, in the methods, and compounds provided herein, the compounds are substantially free of enantiomers (i.e., a racemic, or 50:50 mixture of compounds).
[0060] Similarly, the term "isolated" with respect to a composition refers to a composition that includes at least 85%, 90%, 95%, 98%, or 99% to 100% by weight, of the compound, the remainder comprising other chemical species, enantiomers or diastereomers.
[0061] "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. Where the solvent is water, the solvate is a hydrate.
[0062] "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 containing their natural isotopic composition may also be referred to herein as "non-enriched" atoms. Unless otherwise designated, the atoms of the compounds recited herein are meant to represent any stable isotope of that atom. For example, unless otherwise stated, when a position is designated specifically as hydrogen (H), the position is understood to have hydrogen at its natural isotopic composition.
[0063] "Isotopic enrichment" refers to the percentage of incorporation of an amount of a specific isotope at a given atom in a molecule in the place of that atom's natural isotopic abundance. For example, deuterium (D) enrichment of 1% at a given position means that 1% of the molecules in a given sample contain deuterium at the specified position. Because the naturally occurring distribution of deuterium is about 0.0156%, deuterium enrichment at any position in a compound synthesized using non-enriched starting materials is about 0.0156%. The isotopic enrichment of the compounds provided herein can be determined using conventional analytical methods known to one of ordinary skill in the art, including mass spectrometry and nuclear magnetic resonance spectroscopy.
[0064] "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.
[0065] As used herein, "alkyl," "alkylene," "alkylamino," "dialkylamino," "cycloalkyl," "aryl," "arylene," "alkoxy," "amino," "carboxyl," "heterocycloalkyl," "heteroaryl," "heteroarylene," "carboxyl," and "amino acid" groups optionally comprise deuterium (D) at one, or more positions where hydrogen (H) atoms are present, and wherein the deuterium composition of the atom or atoms is other than the natural isotopic composition.
[0066] Also as used herein, "alkyl," "alkylene," "alkylamino," "dialkylamino," "cycloalkyl," "aryl," "arylene," "alkoxy," "amino," "carboxyl," "heterocycloalkyl," "heteroaryl," "heteroarylene," "carboxyl," and "amino acid" groups optionally comprise carbon-13 ( 13< C) at an amount other than the natural isotopic composition.
[0067] As used herein, term "EC 50 " refers to a dosage, concentration, or amount of a particular test compound that elicits a dose-dependent response at 50% of maximal expression of a particular response that is induced, provoked, or potentiated by the particular test compound.
[0068] As used herein, and unless otherwise specified, the term "IC 50 " refers to an amount, concentration, or dosage of a particular test compound that achieves a 50% inhibition of a maximal response in an assay that measures such response.
[0069] As used herein, the terms "subject", and "patient" are used interchangeably. The terms "subject", and "subjects" refer to an animal, such as a mammal including a non-primate (e.g., a cow, pig, horse, cat, dog, rat, and mouse), and a primate (e.g., a monkey, such as a cynomolgous monkey, a chimpanzee, and a human), and in certain instances, a human. In certain instances, the subject is a farm animal (e.g., a horse, a cow, a pig, etc.), or a pet (e.g., a dog or a cat). In certain instances, the subject is a human.
[0070] As used herein, the terms "therapeutic agent", and "therapeutic agents" refer to any agent(s) which can be used in the treatment, or prevention of a disorder, or one or more symptoms thereof. In certain instances, the term "therapeutic agent" includes a compound provided herein. In certain instances, a therapeutic agent is an agent which is known to be useful for, or has been, or is currently being used for the treatment, or prevention of a disorder, or one, or more symptoms thereof.
[0071] "Therapeutically effective amount" refers to an amount of a compound, or composition that, when administered to a subject for treating a condition, is sufficient to effect such treatment for the condition. A "therapeutically effective amount" can vary depending on, inter alia, the compound, the disease or disorder, and its severity, and the age, weight, etc., of the subject to be treated.
[0072] "Treating" or "treatment" of any disease, or disorder refers, in certain instances, to ameliorating a disease, or disorder that exists in a subject. In another instance, "treating", or "treatment" includes ameliorating at least one physical parameter, which may be indiscernible by the subject. In yet another instance, "treating", or "treatment" includes modulating the disease, or disorder, either physically (e.g., stabilization of a discernible symptom), or physiologically (e.g., stabilization of a physical parameter), or both. In yet another instance, "treating", or "treatment" includes delaying, or preventing the onset of the disease, or disorder, or delaying, or preventing recurrence of the disease, or disorder. In yet another instance, "treating", or "treatment" includes the reduction or elimination of either the disease, or disorder, or retarding the progression of the disease, or disorder, or of one, or more symptoms of the disease, or disorder, or reducing the severity of the disease, or disorder, or of one, or more symptoms of the disease, or disorder.
[0073] As used herein, the terms "prophylactic agent", and "prophylactic agents" as used refer to any agent(s) which can be used in the prevention of a disorder, or one or more symptoms thereof. In certain instances, the term "prophylactic agent" includes a compound provided herein. In certain other instances, the term "prophylactic agent" does not refer a compound provided herein. For example, a prophylactic agent is an agent which is known to be useful for, or has been or is currently being used to prevent, or impede the onset, development, progression, and / or severity of a disorder.
[0074] As used herein, the phrase "prophylactically effective amount" refers to the amount of a therapy (e.g., prophylactic agent) which is sufficient to result in the prevention, or reduction of the development, recurrence, or onset of one or more symptoms associated with a disorder, or to enhance or improve the prophylactic effect(s) of another therapy (e.g., another prophylactic agent).Compounds of Formulae (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII)
[0075] Provided herein are GLP-1 receptor compounds useful for modulating one, or more properties of GLP-1 receptor. The compounds can be prepared as described herein and used for therapy, or diagnosis. In certain instances, the therapy is the treatment of a metabolic disease or condition. In certain instances, the therapy is the treatment of type 2 diabetes.
[0076] The instances described herein include the recited compounds as well as pharmaceutically acceptable salts, hydrates, solvates, stereoisomers, tautomers, and / or mixtures thereof.
[0077] In certain instances, provided is 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, -NMe 2 , or -CF 3 ; Ring B is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Ring C is further unsubstituted or further substituted, and / or bridged; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; L 1< is selected from the group consisting of 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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -CF 2 -, -SO 2 -, -O-, -CF 2 -. -CHF-, -CH(OH)-, - NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; L 4< is absent, or L 4< together with L 1< and Rings A and B form a fused tricycle, and L 5< is absent; L 5< is absent, or L 5< together with L 2< and Rings B and C form a fused tricycle, and L 4< is absent; 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, - B(OH) 2 , and tetrazolyl; each R 6< is independently selected from the group consisting of 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; and R 13< is hydrogen, or alkyl. In certain instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -CF 2 -, -SO 2 -, -O-, -CF 2 -. -CHF-, -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and - N(Me)-.
[0078] In certain instances of Formula (I ), when L 1< is -CH 2 O-, L 4< is absent, and L 5< is absent, then either L 2< is -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -CF 2 -, CHF-, -CHOH-, -NH-, - N(Me)-, or or L 3< is -C(O)-, or both. In certain instances, when L 1< is -CH 2 O-, L 4< is absent, and L 5< is absent, then L 2< is -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, or . In certain instances, when L 1< is -CH 2 O-, L 4< is absent, and L 5< is absent, then L 3< is - C(O)-. In certain instances, when L 1< is -CH 2 O-, L 4< together with L 1< and Rings A and B form a fused tricycle. In certain instances, when L 1< is -CH 2 O-, L 5< together with L 2< and Rings B and C form a fused tricycle. In certain instances, when L 1< is -CH 2 O-, Ring C is substituted or unsubstituted azetidinyl, substituted or unsubstituted pyrrolidinyl, or substituted or unsubstituted piperidinyl.
[0079] In certain instances, A is a ring selected from phenyl and cyclohexyl. In certain instances, Ring C is selected from piperidine and piperazine. In certain instances, Ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran. In certain instances, A is phenyl and Ring C is piperazine. In certain instances, A is phenyl, and Ring C is piperidine. In certain instances, A is phenyl, and Ring C is piperazine, and Ring B is phenyl. In certain instances, A is phenyl, and Ring C is piperazine, and Ring B is furan. In certain instances, A is phenyl, and Ring C is piperidine, and Ring B is phenyl. In certain instances, A is phenyl, and Ring C is piperidine, and Ring B is furan.
[0080] In certain instances, A is a ring selected from phenyl and cyclohexyl. In certain instances, Ring C is selected from substituted piperidine, azetidine, and pyrrolidine. In certain instances, Ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran. In certain instances, A is phenyl and Ring C is piperazine. In certain instances, A is phenyl, and Ring C is piperidine. In certain instances, A is phenyl, and Ring C is substituted piperidine. In certain instances, A is phenyl, and Ring C is azetidine. In certain instances, A is phenyl, and Ring C is pyrrolidine. In certain instances, A is phenyl, Ring C is piperazine, and Ring B is phenyl. In certain instances, A is phenyl, Ring C is piperazine, and Ring B is furan. In certain instances, A is phenyl, Ring C is piperidine, and Ring B is phenyl. In certain instances, A is phenyl, Ring C is piperidine, and Ring B is furan. In certain instances, A is phenyl, Ring C is substituted piperidine, and Ring B is phenyl. In certain instances, A is phenyl, Ring C is substituted piperidine, and Ring B is furan. In certain instances, A is phenyl, Ring C is azetidine, and Ring B is phenyl. In certain instances, A is phenyl, Ring C is azetidine, and Ring B is furan. In certain instances, A is phenyl, Ring C is pyrrolidine, and Ring B is phenyl. In certain instances, A is phenyl, Ring C is pyrrolidine, and Ring B is furan.
[0081] In certain instances, provided is a compound of Formula (Ia), 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, -NMe 2 , or -CF 3 ; Ring B is substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl; Ring C is further unsubstituted or further substituted, and / or bridged; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; W is N, CH, or C; when W is CH, the adjacent dashed lines indicate single bonds; when W is C, one adjacent dashed line indicates a double bond, for instance L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, - C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; L 4< is absent, or L 4< together with L 1< and Rings A and B form a fused tricycle, and L 5< is absent; L 5< is absent, or L 5< together with L 2< and Rings B and C form a fused tricycle, and L 4< is absent; 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< is selected from the group consisting of -COOH, -COCF 3 , - C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , - PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , and tetrazolyl; each R 6< is independently selected from the group consisting of 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; and R 13< is hydrogen, or alkyl. In certain instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -CF 2 -, -SO 2 -, -O-, -CF 2 -. -CHF-, -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-.
[0082] In certain instances of Formula (Ia ), when L 1< is -CH 2 O-, L 4< is absent, and L 5< is absent, then either L 2< is -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, or orL 3< is -C(O)-, or both. In certain instances, when L 1< is -CH 2 O-, L 4< is absent, and L 5< is absent, then L 2< is -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, or In certain instances, when L 1< is -CH 2 O-, L 4< is absent, and L 5< is absent, then L 2< is -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, or In certain instances, when L 1< is -CH 2 O-, L 4< is absent, and L 5< is absent, then L 3< is - C(O)-. In certain instances, when L 1< is -CH 2 O-, L 4< together with L 1< and Rings A and B form a fused tricycle. In certain instances, when L 1< is -CH 2 O-, L 5< together with L 2< and Rings B and C form a fused tricycle.
[0083] In certain instances, A is a ring selected from phenyl, and cyclohexyl. In certain instances, Ring C is selected from piperidine, and piperazine. In certain instances, Ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran. In certain instances, A is phenyl and Ring C is piperazine. In certain instances, A is phenyl, and Ring C is piperidine. In certain instances, A is phenyl, and Ring C is piperazine, and Ring B is phenyl. In certain instances, A is phenyl, and Ring C is piperazine, and Ring B is furan. In certain instances, A is phenyl, and Ring C is piperidine, and Ring B is phenyl. In certain instances, A is phenyl, and Ring C is piperidine, and Ring B is furan.
[0084] In certain instances, provided is a compound of Formula (XXX), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof; wherein W is N, CH, or C; when W is CH, the adjacent dashed lines indicate single bonds; when W is C, one adjacent dashed line indicates a double bond, for instance L 2< is -C(H)=; zero, one, or two of A 1< , A 2< , A 3< , A 4< , and A 5< are N, and the rest are CH, or CR 1< ; zero, one, or two of B 1< , B 2< , B 3< , and B 4< are N, and the rest are CH, or CR 2< ; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -. -C(H)=, -SO 2 -, -O-, -NH-, - N(Me)-, and ; L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO- ;each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, - CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , - SO 2 NHMe, -B(OH) 2 , and tetrazolyl; each R 6< is independently selected from the group consisting of 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 o is an integer from 0 to 4. In certain instances, the compound of Formula (XXX) is selected from compounds 82, 83, 91, 92, and 110, in Table 1.
[0085] In certain instances, provided is a compound of Formula (XXXI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof; wherein W is N, CH, or C; when W is CH, the adjacent dashed lines indicate single; zero, one, or two of A 1< , A 2< , A 3< , A 4< , and A 5< are N, and the rest are CH, or CR 1< ; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -. -C(H)=, -SO 2 -, -O-, -NH-, - N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 3< is independently selected from the group consisting of 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, - CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , - SO 2 NHMe, -B(OH) 2 , 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 instances, the compound of Formula (XXXI) is selected from compounds 97 and 107 in Table 1.
[0086] In certain instances, the compound of Formula (I) is according to Formula (IIa), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein zero, one, or two of A 1< , A 2< , A 3< , A 4< , and A 5< are N, and the rest are CH, or CR 1< ; zero, one, or two of B 1< , B 2< , B 3< , and B 4< are N, and the rest are CH, or CR 2< , wherein, in Formula IIa B 4< is absent; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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; and o is 1, 2, 3, or 4.
[0087] In certain instances, the compound of Formula (I) is according to Formula (IIb), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein zero, one, or two of A 1< , A 2< , A 3< , A 4< , and A 5< are N, and the rest are CH, or CR 1< ; zero, one, or two of B 1< , B 2< , B 3< , and B 4< are N, and the rest are CH or CR 2< , wherein, in Formula IIb, B 4< is absent; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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; and o is 1, 2, 3, or 4.
[0088] In certain instances, the compound of Formula (I) is according to Formula (IIc), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein zero, one, or two of A 1< , A 2< , A 3< , A 4< , and A 5< are N, and the rest are CH, or CR 1< ; zero, one, or two of B 1< , B 2< , B 3< , and B 4< are N, and the rest are CH or CR 2< , wherein, in Formula IIc B 4< is absent; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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; R 14< is hydrogen, cyano, halo, hydroxyl, or methyl; and o is 1, 2, 3, or 4.
[0089] In certain instances, the compound of Formula (I) is according to Formula (IId ), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein zero, one, or two of A 1< , A 2< , A 3< , A 4< , and A 5< are N, and the rest are CH, or CR 1< ; zero, one, or two of B 1< , B 2< , B 3< , and B 4< are N, and the rest are CH or CR 2< , wherein, in Formula IId B 4< is absent; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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; R 14< is hydrogen, cyano, halo, hydroxyl, or methyl; and o is 1, 2, 3, or 4.
[0090] In certain instances, the compound of Formula (I) is according to Formula (IIg), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein zero, one, or two of A 1< , A 2< , A 3< , A 4< , and A 5< are N, and the rest are CH, or CR 1< ; zero, one, or two of B 1< , B 2< , B 3< , and B 4< are N, and the rest are CH or CR 2< , wherein, in Formula IIg , B 4< is absent; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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.
[0091] In certain instances, the compound of Formula (I) is according to Formula (IIh), or a pharmaceutically acceptable salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein zero, one, or two of A 1< , A 2< , A 3< , A 4< , and A 5< are N, and the rest are CH, or CR 1< ; zero, one, or two of B 1< , B 2< , B 3< , and B 4< are N, and the rest are CH or CR 2< , wherein, in Formula IIg , B 4< is absent; zero, one, or two of D 1< , D 2< , and D 3< are N, and the rest are CH, or CR 6< ; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of 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< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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.
[0092] In certain instances, provided is a compound of Formula (III), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -CF 2 -, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, L2 is O. In certain instances, the compound of Formula (III) is selected from 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, 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.
[0093] In certain instances, provided is a compound of Formula (IIIa), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -CF 2 -. -CHF-, or -CH(OH)-, - NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of - COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , - PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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; o is an integer from 0 to 4. In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, L2 is O. In certain instances, 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.
[0094] In certain instances, provided is a compound of Formula (IV), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and ; L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, 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.
[0095] In certain instances, provided is a compound of Formula (V), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, the compound of Formula (V) is selected from compound 71 in Table 1.
[0096] In certain instances, provided is a compound of Formula (VI) or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , - C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , - PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, the compound of Formula (VI) is selected from compounds 34, 62, and 331 in Table 1.
[0097] In certain instances, provided is a compound of Formula (VII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O- -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, 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.
[0098] In certain instances, provided is a compound of Formula (VIII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , - C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , - PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, the compound of Formula (VIII) is selected from compound 44 in Table 1.
[0099] In certain instances, provided is a compound of Formula (IX), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, the compound of Formula (IX) is selected from compounds 27 and 28 in Table 1.
[0100] In certain instances, provided is a compound of Formula (X), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, the compound of Formula (X) is selected from compound 4, 272, and 284 in Table 1.
[0101] In certain instances, provided is a compound of Formula (XI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, - COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , - PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, the compound of Formula (XI) is selected from compounds 53, 90, 121, 142, and 143 in Table 1.
[0102] In certain instances, provided is a compound of Formula (XII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, the compound of Formula (XII) is compound 108 in Table 1.
[0103] In certain instances, provided is a compound of Formula (XIII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, the compound of Formula (XIII) is selected from compounds 88, 178, and 179 in Table 1.
[0104] In certain instances, provided is a compound of Formula (XIV), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, the compound of Formula (XIV) is selected from compounds 85, 139, and 220 in Table 1.
[0105] In certain instances, provided is a compound of Formula (XV), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, L2 is O. In certain instances, 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.
[0106] In certain instances, provided is a compound of Formula (XVI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, L2 is O. In certain instances R 14< is CH 2 F or CH 2 OH. In certain instances, 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.
[0107] In certain instances, provided is a compound of Formula (XVIa), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -CF 2 -. -CHF-, or - CH(OH)-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of - COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , - PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , and tetrazolyl; each R 11< is hydrogen or alkyl; each R 12< is 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. In certain instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, - C(H)=, -CF 2 -, -SO 2 -, -O-, -CF 2 -. -CHF-, -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, L2 is O. In certain instances, 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.
[0108] In certain instances, provided is a compound of Formula (XVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, - CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, the compound of Formula (XVII) is selected from compound 106 in Table 1.
[0109] In certain instances, provided is a compound of Formula (XVIII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is - CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , - C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , - PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, the compound of Formula (XVIII) is compound 87 in Table 1.
[0110] In certain instances, provided is a compound of Formula (XXV), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -CF 2 -. -CHF-, or -CH(OH)-, -NH-, -N(Me)-, and ; L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of -COOH, -COCF 3 , - C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , - PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , and tetrazolyl; each R 11< is hydrogen or alkyl; each R 12< is 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; q is an integer from 0 or 1. In certain instances, p is 0; and q is 0. In certain instances, p is 1; and q is 0. In certain instances, p is 0; and q is 1. In certain instances, p is 1; and q is 1. In certain instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -CF 2 -, -SO 2 -, -O-, -CF 2 -. -CHF-, -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of - NH- and -N(Me)-. In certain instances, the compound of Formula (XXV) is compound 286 in Table 1.
[0111] In certain instances, provided is a compound of Formula (XXVI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 1< is selected from the group consisting of -O-, -CH 2 -, -NH-, -N(Me)-, -N(Et)-, -OCH 2 -, - OC(H,Me)-, -CHaO-, -NHCH 2 -, -N(Me)CH 2 -, and -SO 2 NH-; L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is - CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, - B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, - C(H)=, -SO 2 -, -O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is selected from the group consisting of -NH- and -N(Me)-. In certain instances, L2 is O. In certain instances, 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. The compound recited in appended claim 1 is compound 485 or a pharmaceutically acceptable salt or solvate thereof.
[0112] In certain instances, provided is a compound of Formula (XXVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein A is -NMe 2 or -N(CH 3 )cylcohexane; L 1< is absent; W is N, CR 14< , or C; when W is CR 14< , the adjacent dashed line indicates a single bond; when W is C, the adjacent dashed line indicates a double bond or L 2< is -C(H)=; L 2< is selected from the group consisting of a bond, - C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of - COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , - PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, the compound of Formula (XXVII) is selected from compounds 1 and 62 in Table 1.
[0113] In certain instances, provided is a compound of Formula (XXXIX), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, - B(OH) 2 , and tetrazolyl; each R 6< is independently selected from the group consisting of 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, each R 6< is independently selected from the group consisting of F, and methyl. In certain instances, each R 6< is F. In certain instances, the compound of Formula (XXXIX) is selected from compounds 224, 300, 303, 309, 310, 317, and 320 in Table 1.
[0114] In certain instances, provided is a compound of Formula (XL), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, - B(OH) 2 , and tetrazolyl; each R 6< is independently selected from the group consisting of 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, each R 6< is independently selected from the group consisting of F, and methyl. In certain instances, each R 6< is F. In certain instances, the compound of Formula (XL) is selected from compounds 302, 325, 336, 344, 359, and 365 in Table 1.
[0115] In certain instances, provided is a compound of Formula (XLI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, - B(OH) 2 , and tetrazolyl; each R 6< is independently selected from the group consisting of 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, each R 6< is independently selected from the group consisting of F, and methyl. In certain instances, each R 6< is F. In certain instances, each R 6< is methyl. In certain instances, 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 instances, provided is a compound of Formula (XLII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, - B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, - C(H)=, -SO 2 -, -O-, -CF 2 -. -CHF-, or -CH(OH)-, and . In certain instances, L 2< is -O-. In certain instances, the compound of Formula (XLII) is selected from compounds 370, 371, 373, 375, 377, 378, 486, and 513 in Table 1.
[0117] In certain instances, provided is a compound of Formula (XLIII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 -, or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5< is selected from the group consisting of -COOH, -COCF 3 , - C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , - PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, -B(OH) 2 , and tetrazolyl; each R 6< is independently selected from the group consisting of 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; r is an integer from 0 to 3. In certain instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is -O-. In certain instances, each R 6< is independently selected from the group consisting of F, and methyl. In certain instances, each R 6< is F. In certain instances, each R 6< is methyl. In certain instances, the compound of Formula (XLIII) is c selected from compounds 487 and 488 in Table 1.
[0118] In certain instances, provided is a compound of Formula (XLII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, - B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, - C(H)=, -SO 2 -, -O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is -O-. In certain instances, the compound of Formula (XLIV) is compound 372 in Table 1.
[0119] In certain instances, provided is a compound of Formula (XLV), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, - B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, - C(H)=, -SO 2 -, -O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is -O-. In certain instances, the compound of Formula (XLV) is compound 379 in Table 1.
[0120] In certain instances, provided is a compound of Formula (XLVI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, - B(OH) 2 , 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 instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, - C(H)=, -SO 2 -, -O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, L 2< is -O-. In certain instances, the compound of Formula (XLVI) is selected from compounds125 and 129 in Table 1.
[0121] In certain instances, provided is a compound of Formula (XLI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof: wherein L 1< is selected from the group consisting of -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 selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -NH-, -N(Me)-, and L 3< is -CH 2 - or -C(O)-; each R 1< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 2< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; each R 3< is independently selected from the group consisting of alkyl, substituted alkyl, halo, cyano, azido, alkoxy, haloalkoxy, and R 11< R 12< NCO-; R 4< is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; R 5< is selected from the group consisting of -COOH, -COCF 3 , -C(OH)CF 3 , -CONHCN, -CONHOH, CONHOMe, -CONHSO 2 N(Me) 2 , -PO 3 H 2 , -PO(Me)(OH), -SO 3 H, -SO 2 NH 2 , -SO 2 NHMe, - B(OH) 2 , and tetrazolyl; each R 6< is independently selected from the group consisting of 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 o to 4; and r is an integer from 0 to 3. In certain instances, L 2< is selected from the group consisting of a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, - O-, -CF 2 -. -CHF-, or -CH(OH)-, and In certain instances, each R 6< is independently selected from the group consisting of F, and methyl. In certain instances, each R 6< is F. In certain instances, each R 6< is methyl. In certain instances, the compound of Formula (XLVII) is compound 491 in Table 1.
[0122] In certain instances, provided is a compound of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein each R 2< and R 3< is H, or F.
[0123] In certain instances, provided is a compound of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein m is 0; and o is 0.
[0124] In certain instances, provided is a compound of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein W is N, or CH.
[0125] In certain instances, provided is a compound of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein W is C.
[0126] In certain instances, provided is a compound of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein W is CH.
[0127] In certain instances, provided is a compound of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein W is N.
[0128] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein W is CR 14< .
[0129] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, 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 instances, provided is a compound of any of Formulas (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically 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 instances, provided is a compound of any of Formulas (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4< is oxetan-2-yl-methyl.
[0132] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4< is (2S)-oxetan-2-yl-methyl.
[0133] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl.
[0134] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4< is selected from the group consisting of (S)-buta-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-lyl-methyl, methoxyethan-2-yl, 1-(2-methoxyethyl)-cycloprop-1-yl-methyl, and 2-oxabicyclo[2.1.1]hexa-1-yl-methyl.
[0135] In certain instances, provided is a compound of Formula (XXX), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4< is H.
[0136] In certain instances, provided is a compound of Formula (XXX), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4< is selected from the group consisting of oxelan-3-yl-methyl and 1,3-oxazol-2-yl-methyl.
[0137] In certain instances, provided is a compound of Formula (XXX) and (XXXI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4< is (3R)-oxelan-3-yl-methyl.
[0138] In certain instances, provided is a compound of Formula (XXX) and (XXXI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 4< is 1,3-oxazol-2-yl-methyl.
[0139] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 5< is -COOH, or - COOMe.
[0140] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 5< is -COOH
[0141] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 5< is tetrazolyl.
[0142] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein R 5< is 1H-1,2,3,4-tetrazol-5-yl.
[0143] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -CH 2 -, -C(O)-, or -SO 2 -.
[0144] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is a bond, -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -CF 2 -. -CHF-, or -CH(OH)-.
[0145] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -CH= or -O-.
[0146] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -CF 2 -, -CHF-, or -CH(OH)-.
[0147] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -NH- or - N(Me)-.
[0148] In certain instances, provided is a compound of Formula (XXX), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is a bond.
[0149] In certain instances, provided is a compound of Formula (XXXI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -CH 2 -.
[0150] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 3< is -CH 2 -.
[0151] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 3< is -C(O)-.
[0152] In certain instances, provided is a compound of Formulas (XXX), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -CH 2 O-, or -OCH 2 -.
[0153] In certain instances, provided is a compound of Formula (XXXI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -CH 2 O-, or -OCH 2 .
[0154] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -CH 2 O-; and L 2< is -CH 2 - or -CO -.
[0155] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -CH 2 O-; and L 3< is -C(O)-.
[0156] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), and (XXXI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -O-.
[0157] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -CH 2 -.
[0158] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -NH-.
[0159] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -N(Me)-.
[0160] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -N(Et)-.
[0161] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -OCH 2 -.
[0162] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), and (XXXI), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -OC(H,Me)-.
[0163] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -CH 2 O-.
[0164] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -NHCH 2 -.
[0165] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -N(Me)CH 2 -.
[0166] In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 1< is -SO 2 NH-.
[0167] In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), a (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; and L 2< is -C(O)-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; and L 2< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; and L 2< is -C(H)=. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; and L 2< is -SO 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI ), (XXXIX ), and (XL-XLVII), L 1< is -O-; and L 2< is -NH-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; and L 2< is -N(Me)-. In certain instances 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< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -CH 2 -; and L 3< is -CH 2 -. In certain instances 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< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -SO 2 -; and L 3< is -CH 2 -. In certain instances 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< is -CH 2 -. In certain instances 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< is - CH 2 -. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -CH 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -SO 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; ; and R 3< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI), L 1< is -O-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is - SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -O-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In any instance according to this paragraph, R 1< can be selected from H, Cl, F, Me, -CF 3 , -OMe, -CN, -C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3R)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3S)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (S)-buta-4-yl-1,3-diol. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIIV), R 4< is butan-1-yl-one. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-(Fluoromethyl)-cycloprop-1-yl-methyl. In certain instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is isoxazol-5-yl-methyl. In certain instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-methoxy-cycloprop-lyl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is methoxyethan-2-yl. In certain instances 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 instances 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 instances 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 instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -NH-. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -N(Me)-.
[0168] In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; and L 2< is -C(O)-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; and L 2< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; and L 2< is - C(H)=. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; and L 2< is -SO 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; and L 2< is -NH-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; and L 2< is - N(Me)-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(O)-; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI), L 1< is - CH 2 O-; L 2< is -CH 2 -; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(H)=; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -SO 2 -; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -NH--; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -N(Me)- -; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1< is -CH 2 O-; L 2< is -C(O)-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -CH 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(H)=; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -SO 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -NH-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -N(Me)-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; ; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(O)-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -CH 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(H)=; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -SO 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -NH-; L 3< is - CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -N(Me)-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(O)-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -CH 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -NH-; L 3< is - CH 2 -; and R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -N(Me)-; L 3< is -CH 2 -; and R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -C(H)=; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -CH 2 O-; L 2< is -SO 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In any instance according to this paragraph, R 1< can be selected from H, Cl, F, Me, -CF 3 , -OMe, -CN, -C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3R)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3S)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (S)-buta-4-yl-1,3-diol. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is butan-1-yl-one. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is 1-(Fluoromethyl)-cycloprop-1-yl-methyl. In certain instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is isoxazol-5-yl-methyl. In certain instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is 1-methoxy-cycloprop-lyl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is methoxyethan-2-yl. In certain instances 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 instances 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 instances 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 instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -NH-. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -N(Me)-.
[0169] In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; and L 2< is -C(O)-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; and L 2< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; and L 2< is - C(H)=. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; and L 2< is -SO 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI), L 1< is -OCH 2 -; and L 2< is -NH-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; and L 2< is -N(Me)-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(O)-; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -CH 2 -; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(H)=; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -SO 2 -; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -NH-; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -N(Me)- ; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIVII), L 1< is -OCH 2 -; L 2< is -NH-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1< is -OCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1< is -OCH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIVII), L 1< is -OCH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(O)-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -CH 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(H)=; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -SO 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -NH-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -N(Me)-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1< is -OCH 2 -; L 2< is -C(O)-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -CH 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -C(H)=; L 3< - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -SO 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -NH-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In any instance according to this paragraph, R 1< can be selected from H, Cl, F, Me, -CF 3 , -OMe, -CN, -C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3R)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3S)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (S)-buta-4-yl-1,3-diol. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is butan-1-yl-one. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), R 4< is 1-(Fluoromethyl)-cycloprop-1-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is 1-hydroxyl-cycloprop-1-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is isoxazol-5-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is (1-methyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-methoxy-cycloprop-lyl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is methoxyethan-2-yl. In certain instances 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 instances 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 instances 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 instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -NH-. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -N(Me)-.
[0170] In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH- and L 2< is -C(O)-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH- and L 2< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI), L 1< is -NH-; and L 2< is -C(H)=. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX ), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; and L 2< is -SO 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; and L 2< is -NH-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; and L 2< is -N(Me)-. In certain instances 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< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -CH 2 -; and L 3< is -CH 2 -. In certain instances 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< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -SO 2 -; and L 3< is -CH 2 -. In certain instances 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< is -CH 2 -. In certain instances 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 3< is -CH 2 -. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -CH 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -SO 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -NH-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX ), and (XL-XLVII ), L 1< is -NH-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 3< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1< is -NH-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NH-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In any instance according to this paragraph, R 1< can be selected from H, Cl, F, Me, -CF 3 , -OMe, -CN, -C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3R)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3S)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (S)-buta-4-yl-1,3-diol. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is butan-1-yl-one. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), is 1-(Fluoromethyl)-cycloprop-1-yl-methyl. In certain instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is isoxazol-5-yl-methyl. In certain instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-methoxy-cycloprop-lyl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is methoxyethan-2-yl. In certain instances 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 instances 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 instances 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 instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -NH-. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -N(Me)-.
[0171] In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)- and L 2< is -C(O)-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)- and L 2< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)- and L 2< is - SO 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; and L 2< is -NH-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; and L 2< is -N(Me)-. In certain instances 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< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -CH 2 -; and L 3< is -CH 2 -. In certain instances 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< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -SO 2 -; and L 3< is -CH 2 -. In certain instances 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< is -CH 2 -. In certain instances 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 3< is -CH 2 -. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -CH 2 - ; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 3< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is - COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; ; and R 3< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 3< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 3< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI), L 1< is -N(Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -CH 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 3< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 3< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In any instance according to this paragraph, R 1< can be selected from H, Cl, F, Me, -CF 3 , -OMe, -CN, -C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3R)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3S)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (S)-buta-4-yl-1,3-diol. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is butan-1-yl-one. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-(Fluoromethyl)-cycloprop-1-yl-methyl. In certain instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is isoxazol-5-yl-methyl. In certain instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-methoxy-cycloproplyl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is methoxyethan-2-yl. In certain instances 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 instances 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 instances 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 instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -NH-. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -N(Me)-.
[0172] In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; and L 2< is -C(O)-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; and L 2< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; and L 2< is - C(H)=. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; and L 2< is -SO 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; and L 2< is -NH-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; and L 2< is - N(Me)-. In certain instances 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< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -CH 2 -; and L 3< is -CH 2 -. In certain instances 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< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -SO 2 -; and L 3< is -CH 2 -. In certain instances 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 3< is -CH 2 -. In certain instances 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< is -CH 2 -. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -CH 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -SO 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIVI), L 1< is -N(Et)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-mehyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -CH 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -SO 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; ; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -CH 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX ), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -SO 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -N(Et)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In any instance according to this paragraph, R 1< can be selected from H, Cl, F, Me, -CF 3 , -OMe, -CN, -C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3R)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3S)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (S)-buta-4-yl-1,3-diol. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is butan-1-yl-one. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX ), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is 1-(Fluoromethyl)-cycloprop-1-yl-methyl. In certain instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is isoxazol-5-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is (1-methyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-methoxy-cycloprop-lyl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is methoxyethan-2-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is 1-(2-methoxyethyl)-cycloprop-1-yl-methyl. In certain instances 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 instances 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 instances 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 instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX ), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -NH-. In certain instances, provided is a compound of any of Formulas (I) - (XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -N(Me)-.
[0173] In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; and L 2< is -C(O)-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; and L 2< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; and L 2< is - C(H)=. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; and L 2< is -SO 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; and L 2< is -NH-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; and L 2< is - N(Me)-. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(O)-; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -CH 2 -; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX ), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(H)=; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -SO 2 -; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -NH-; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -N(Me)-; and L 3< is -CH 2 -. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI), L 1< is - NHCH 2 -; L 2< is -NH-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is - C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is - COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX ), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(O)-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; ; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX ), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -SO 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX ), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(O)-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -CH 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -SO 2 -; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -NH-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -C(O)-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is - C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -NHCH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In any instance according to this paragraph, R' can be selected from H, Cl, F, Me, -CF 3 , -OMe, -CN, -C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3R)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX ), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3S)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is (S)-buta-4-yl-1,3-diol. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is butan-1-yl-one. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is 1-(Fluoromethyl)-cycloprop-1-yl-methyl. In certain instances 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 instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is isoxazol-5-yl-methyl. In certain instances 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 instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is 1-methoxy-cycloprop-lyl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is methoxyethan-2-yl. In certain instances 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 instances 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 instances 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 instances 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 instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLIII ), R 4< is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain instances, provided is a compound of any of Formulas (I ) - (XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLII ), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -NH-. In certain instances, provided is a compound of any of Formulas (I ) - (XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -N(Me)-.
[0174] In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; and L 2< is -C(O)-. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; and L 2< is -CH 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; and L 2< is -C(H)=. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; and L 2< is -SO 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), and (XXXI ), L 1< is - N(Me)CH 2 -; and L 2< is -NH-. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; and L 2< is -N(Me)-. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(O)-; and L 3< is -CH 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -CH 2 -; and L 3< is -CH 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(H)=; and L 3< is -CH 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -SO 2 -; and L 3< is -CH 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -NH-; and L 3< is -CH 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -N(Me)-; and L 3< is -CH 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -NH-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is - C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLIII ), L 1< is -N(Me)CH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is - C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; ; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -N(Me)-; L 3< is - CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(O)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -C(H)=; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -NH-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -N(Me)CH 2 -; L 2< is -N(Me)-; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In any instance according to this paragraph, R 1< can be selected from H, Cl, F, Me, -CF 3 , -OMe, -CN, -C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is azetidine-3-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is (3R)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is (3S)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is (S)-buta-4-yl-1,3-diol. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is butan-1-yl-one. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is 1-(Fluoromethyl)-cycloprop-1-yl-methyl. In certain instances 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 instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is isoxazol-5-yl-methyl. In certain instances 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 instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is 1-methoxy-cycloprop-lyl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is methoxyethan-2-yl. In certain instances 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 instances 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 instances 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 instances 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 instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), R 4< is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain instances, provided is a compound of any of Formulas (I ) - (XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -NH-. In certain instances, provided is a compound of any of Formulas (I ) - (XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), or a pharmaceutically salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof, wherein L 2< is -N(Me)-.
[0175] In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; and L 2< is -C(O)-. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; and L 2< is -CH 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; and L 2< is -C(H)=. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and ( XL-XLVII ), L 1< is -OC(H,Me)- and L 2< is -SO 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; and L 2< is -NH-. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; and L 2< is -N(Me)-. In certain instances 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< is - CH 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -CH 2 -; and L 3< is -CH 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), a (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -C(H)=; and L 3< is -CH 2 -. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -SO 2 -; and L 3< is -CH 2 -. In certain instances 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< is -CH 2 -. In certain instances 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< is -CH 2 -. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; and R 2< and R 3< are each H. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (2S)-oxetan-2-yl-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; and R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; ; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is -COOH. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I )-(XVIII ), (XXV ) - (XXVII ), (XXX ), (XXXI ), (XXXIX ), and (XL-XLVII ), L 1< is -OC(H,Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OC(H,Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (2S)-oxetan-2-yl-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX ), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OC(H,Me)-; L 2< is -CH 2 -; L 3< is -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1< is -OC(H,Me)-; L 2< is -SO 2 -; L 3< is -CH 2 -; R 2< and R 5< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 3< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In certain instances 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 -CH 2 -; R 2< and R 3< are each H; R 4< is (1-ethyl-1H-imidazol-5-yl)-methyl; and R 5< is tetrazolyl, for instance 1H-1,2,3,4-tetrazol-5-yl. In any instance according to this paragraph, R 1< can be selected from H, Cl, F, Me, -CF 3 , -OMe, -CN, -C(O)NMe 2 , alkyl, propyl, isopropyl, and cyclopropyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3R)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (3S)-azetidine-3-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is (S)-buta-4-yl-1,3-diol. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), and (XXXI) R 4< is butan-1-yl-one. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-(cyanomethyl)-cycloprop-1-yl-methyl. In certain instances of any of Formulas (I)-(XVIII), (XXV) - (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4< is 1-(Fluoromethyl)-cycloprop-1-yl-methyl. In certain instances 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 instances of any of Formulas (I)-(XVI...
Claims
1. A compound which is 2-{[(2S,4S)-4-({2-[(2,4-difluorophenoxy)methyl]pyrimidin-4-yl}oxy)-2-methylpiperidin-1-yl]methyl}-1-{[(2S)-oxetan-2-yl]methyl}-1H-1,3-benzodiazole-6-carboxylic acid: or a pharmaceutically acceptable salt or solvate thereof.
2. The compound of claim 1, which is:
3. The compound of claim 1, which is a pharmaceutically acceptable salt of:
4. A pharmaceutical composition comprising the compound of any one of the preceding claims, and one or more pharmaceutically acceptable carriers, excipients, or diluents.
5. The compound of any one of claims 1 to 3, or the pharmaceutical composition of claim 4, for use in therapy.
6. The compound of any one of claims 1 to 3, or the pharmaceutical composition of claim 4, for use in the treatment of type 2 diabetes.