GPCR receptor agonists, pharmaceutical compositions containing the same, and methods for using the same.
Patent Information
- Application Number
- JP2026092219
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2021-11-02
- Filing Date
- 2026-06-01
- Publication Date
- 2026-09-08
AI Technical Summary
があることが示されている。Doyle and Egan,2007(上記)。GLP-1受容体は有望な治療標的であるが、現在まで承認されているGLP-1受容体医薬品はほんの一握りであり、これらのほとんどまたはすべてがペプチドまたはポリペプチド医薬品である。
Smart Images

Figure 2026143549000001_ABST
Abstract
Description
[Technical Field]
[0001] Cross-reference of related applications This application is a PCT international application claiming the benefits of U.S. Provisional Application No. 63 / 274,893 filed on 2 November 2021, U.S. Provisional Application No. 63 / 183,612 filed on 3 May 2021, and U.S. Provisional Application No. 63 / 143,025 filed on 28 January 2021, the entire contents of which are incorporated herein by reference.
[0002] This specification provides GLP-1 receptor modulator compounds; pharmaceutical compositions comprising the compounds; methods for producing the compounds; and methods for using the compounds and compositions for therapeutic purposes. The compounds and compositions are useful, for example, in methods for treating and preventing metabolic diseases or conditions, methods for detecting metabolic diseases or conditions, and methods for diagnosing metabolic diseases or conditions. [Background technology]
[0003] Diabetes is a serious chronic disease that occurs when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces. Complications of diabetes include damage to the heart, blood vessels, eyes, kidneys, and nerves. Diabetes can increase the risk of heart disease and stroke. The consequences include serious impacts on quality of life, health, and mortality. (WHO Global Report on Diabetes, 2016, World Health Organization). As of 2017, approximately 462 million people worldwide, or about 6.28% of the population, had type 2 diabetes, and this prevalence is visibly increasing. (Khan et al., 2020, J.Epidemiol.Glob.Health 10(1):107-111). The global economic burden of diabetes was estimated at $1.3 trillion in 2015 and is projected to increase to $2.1 trillion by 2030. Bommer et al., 2018, Diabetes Care 41(5):963-970. Approximately 90-95% of all diabetes cases are type 2 diabetes. Tripathi & Srivastava, 2016, Med.Sci.Monit.12(7):RA130-147.
[0004] The glucagon-like peptide-1 receptor (GLP-1 receptor, or GLP1R) has emerged as a potential target for treating type 2 diabetes. Its ligand, glucagon-like peptide-1 (GLP-1), promotes glucose-induced insulin secretion and increases insulin synthesis, among many other effects. Doyle and Egan, 2007, Pharmacol.Ther. 113(3):546-593. GLP-1 is known to slow gastric emptying in humans, suppress food intake, increase satiety, and reduce weight. Shah and Vella, 2014 Rev Endocr Metab Disord. 15(3):181-187. Activation of the GLP-1 receptor has been shown to have beneficial effects on insulin secretion, as well as on maintaining glucose sensing, transcription, synthesis, proliferation, and survival of beta cells. Doyle and Egan, 2007 (see above). 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.
[0005] Additional therapies are needed to treat metabolic diseases and conditions such as type 2 diabetes. Small molecules targeting the GLP-1 receptor should provide safe, stable, and easily administered treatments for metabolic diseases and conditions such as type 2 diabetes. [Overview of the project]
[0006] This specification provides GLP-1 receptor modulator compounds of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), as well as their subformulas, compositions comprising the compounds, methods for producing the compounds, and methods for using the compounds and crude products for therapeutic and diagnostic purposes. Compounds of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), as well as their subformulas, and embodiments thereof, are useful for modulating the activity of the GLP-1 receptor. In certain embodiments, the compounds may be used to agonize the activity of the GLP-1 receptor. In certain embodiments, the compounds may be used to treat diseases or conditions modulated by the GLP-1 receptor.
[0007] In one embodiment, a compound of formula (I), a pharmaceutically acceptable salt thereof, or a stereoisomer is provided: [ka] In the formula, A is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted cycloalkyl, -NMe2, or -CF3; Ring B is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, or a substituted or unsubstituted bicyclic ring; Ring C is a substituted or unsubstituted heterocycloalkyl, or a substituted or unsubstituted heterocycloalkenyl, as shown in the figure L 3 It includes at least one N bonded to it; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 and; W is N, CR 14 , or C; W is CR 14 If W is C, adjacent dashed lines indicate a single bond; if W is C, adjacent dashed lines indicate a double bond or L2 is -C(H)=; L 1 is selected from the group consisting of a bond, -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 is selected from the group consisting of a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and
Chemical Formula
Chemical Formula
[0008] In one embodiment, a compound of formula (Ia), or a pharmaceutically acceptable salt thereof, or a stereoisomer is provided: [ka] In the formula, A is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted cycloalkyl, -NMe2, or -CF3; Ring B is a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; Ring C is either further unsubstituted, further substituted, and / or crosslinked; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 and; W is N, CH, or C; if W is CH, adjacent dashed lines indicate single bonds; When W is C, one adjacent dashed line indicates a double bond, for example, L 2 -C(H)=; L 1 It is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; L 4 It does not exist, or L 4 is L 1 Furthermore, together with rings A and B, they form a condensed triring, and L 5 It does not exist; L 5 It does not exist, or L 5 is L 2 Furthermore, together with rings B and C, they form a condensed triring, and L 4 It does not exist; R 4 This includes unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylalkylene; R 5-COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; Each R 6 These are alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, and R 11 R 12 NCO- and R 11 R 12 Independently selected from a group consisting of N-; R 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; and R 13 is hydrogen or alkyl; In the formula, L 1 is -CH2O-, L 4 If it does not exist, and L 5 If it does not exist, L 2 These are -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, or [ka] is or L 3 It is either -C(O)- or both.
[0009] In one embodiment, a compound of formula (XXX), or a pharmaceutically acceptable salt thereof, or a stereoisomer is provided: [ka] In the formula, W is N, CH, or C; when W is CH, adjacent dashed lines indicate single bonds; when W is C, adjacent dashed lines indicate double bonds, for example, L2 is -C(H)=; A 1 , A 2 , A 3 , A 4 , and A 5 0, 1, or 2 are N, and the remainder are CH or CR 1 ; B 1 , B 2 , B 3 , and B 4 0, 1, or 2 are N, and the remainder are CH or CR 2 ; D 1 , D 2 , and D 3 0, 1, or 2 are N, and the remainder are CH or CR 6 ; L 1 is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 is a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and [[Formula]] is selected from the group consisting of; L 3 is -CH2- 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 3is 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, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2,
Chemical Structure
[0010] In one aspect, provided herein is a compound of Formula XXXI, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof:
Chemical Structure
[0011] In certain embodiments, the compounds are useful in methods for treating and preventing metabolic diseases and conditions, methods for detecting metabolic diseases and conditions, and methods for diagnosing metabolic diseases and conditions.
[0012] In another embodiment, compositions comprising compounds of formula (I), (Ia), (XXX), or (XXXI) are provided. In some embodiments, the compositions are pharmaceutical compositions. Any suitable pharmaceutical composition may be used. In further embodiments, kits comprising compounds of formula (I), (Ia), (XXX), or (XXXI), embodiments thereof, or pharmaceutical compositions thereof are provided herein.
[0013] In other embodiments, this specification provides methods using the compounds or compositions described herein. In some embodiments, the method is for treatment. In some embodiments, the method is a diagnostic method. In some embodiments, the method is an analytical method. In some embodiments, the compounds or compositions described herein are used to treat a disease or condition. In some embodiments, this disease or condition is selected from metabolic diseases or conditions. In certain embodiments, this disease is type 2 diabetes mellitus.
[0014] Furthermore, this specification also provides the use of the compounds and compositions thereof described herein for the treatment of metabolic diseases or conditions. Furthermore, this specification also provides the use of the compounds and compositions thereof described herein for the treatment of type 2 diabetes. [Brief explanation of the drawing]
[0015] [Figure 1] This shows the intravenous glucose tolerance test (IVGTT) in cynomolgus monkeys. [Modes for carrying out the invention]
[0016] This specification describes GLP-1 receptor compounds useful for treating metabolic diseases or conditions such as type 2 diabetes.
[0017] definition Unless otherwise defined, all technical terms, notations, and other scientific terms used herein have meanings that are generally understood by those skilled in the art to which this disclosure relates. Where applicable, terms that have generally understood meanings are defined herein for clarification and / or for immediate reference. The techniques and procedures described or referenced herein are generally well understood and commonly used by those skilled in the art using conventional methodologies. Where necessary, procedures involving the use of commercially available kits and reagents are generally performed in accordance with the protocols and conditions set forth by the manufacturers, unless otherwise noted.
[0018] As used herein, unless the context clearly indicates otherwise, the singular forms “a,” “an,” and “the” refer to multiple things.
[0019] The term "approximately" indicates and encompasses the given value and its upper and lower range. In certain embodiments, the term "approximately" indicates a specified value ± 10%, ± 5%, or ± 1%. In certain embodiments, the term "approximately" indicates a specified value ± 1 standard deviation of that value. In certain embodiments, for example, on a logarithmic scale (e.g., pH), the term "approximately" indicates a specified value ± 0.3, ± 0.2, or ± 0.1.
[0020] When referring to the compounds provided herein, the following terms have the meanings set forth below unless otherwise specified. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art. If there are multiple definitions of a term herein, the definition in this section shall prevail unless otherwise stated.
[0021] "Alkoxy" and "alkoxyl" refer to the -OR" group, where R is alkyl or cycloalkyl. Examples of alkoxy groups in certain embodiments include methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexoxy, and 1,2-dimethylbutoxy.
[0022] As used herein, the term “alkoxyamine” refers to an alkylene-O-NH2 group, where alkylene is as defined herein. In some embodiments, the alkoxyamine group may react with an aldehyde to form an oxime residue. Examples of alkoxyamine groups include -CH2CH2-O-NH2 and -CH2-O-NH2.
[0023] The term "alkyl," as used herein, refers to saturated linear or branched hydrocarbons unless otherwise specified. In certain embodiments, alkyl groups are primary, secondary, or tertiary hydrocarbons. In certain embodiments, alkyl groups contain 1 to 10 carbon atoms (i.e., C1 to C1). 10 Alkyl). In certain embodiments, alkyl is a lower alkyl, for example, C 1-6 These include alkyl groups. In certain embodiments, the alkyl group is selected from the group consisting of methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, t-butyl, pentyl, isopentyl, neopentyl, hexyl, isohexyl, 3-methylpentyl, 2,2-dimethylbutyl, and 2,3-dimethylbutyl. In certain embodiments, "substituted alkyl" refers to an alkyl group substituted with one, two, or three groups independently selected from halogens (e.g., fluoro(F), chloro(Cl), bromo(Br), or iodo(I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, alkoxy, aryl, heteroaryl, cycloalkyl, cyano, oxo, alkyne, and heterocycloalkylalkylene. In some embodiments, the alkyl group is unsubstituted.
[0024] As used herein, the term “alkylene” refers to a divalent alkyl group as defined herein, unless otherwise specified. “Substituted alkylene” refers to an alkylene group that has been substituted as described herein. In some embodiments, the alkylene is unsubstituted.
[0025] "Alkenyl" refers to an olefinic unsaturated hydrocarbon group having up to about 11 carbon atoms, or 2 to 6 carbon atoms (e.g., "lower alkenyl"), which may be linear or branched in certain embodiments, and having at least one or 1 to 2 olefinic unsaturated moieties. "Substitutive alkenyl" refers to an alkenyl group that has been substituted for an alkyl group as described herein.
[0026] "Alkenylene" refers to a divalent alkenyl as defined herein. Lower alkenylenes are, for example, C2-C6 alkenylenes.
[0027] "Alkynyl" refers to an acetylene unsaturated hydrocarbon group having up to about 11 carbon atoms, or 2 to 6 carbon atoms (e.g., "lower alkynyl"), which may be linear or branched in certain embodiments, and having at least one or 1 to 2 acetylene unsaturated moieties. Non-limiting examples of alkynyl groups include acetylene (-C≡CH) and propargyl (-CH2C≡CH). "Substituted alkynyl" refers to an alkynyl group in which an alkyl group has been substituted as described herein.
[0028] "Alkynylene" refers to a divalent alkynyl as defined herein. Lower alkenylenes are, for example, C2-C6 alkynylenes.
[0029] "Amino" refers to -NH2.
[0030] As used herein, the term "alkylamino" refers to the group -NHR” unless otherwise specified, where R” is, for example, C as defined herein. 1-10 It is alkyl. In certain embodiments, alkylamino is C 1-6 It is an alkylamino compound.
[0031] As used herein, the term “dialkylamino” refers to the group -NR”R” unless otherwise specified, where each R” independently represents C as defined herein. 1-10 It is alkyl. In certain embodiments, dialkylamino is di-C 1-6 It is an alkylamino compound.
[0032] As used herein, the term “aryl” refers to phenyl, biphenyl, or naphthyl unless otherwise specified. This term includes both substituted and unsubstituted moieties. The aryl group may be substituted with any described moieties, including but not limited to one or more moieties (e.g., one, two, or three moieties in some embodiments) selected from the group consisting of halogens (e.g., fluoro(F), chloro(Cl), bromo(Br), or iodo(I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, arylamino, alkoxy, aryloxy, nitro, cyano, sulfonic acid, sulfate, phosphonic acid, phosphate, and phosphonate, where, as will be understood by those skilled in the art, each moiety is independently unprotected or protected as needed (e.g., Greene et al., Protective Groups in Organic Synthesis, John Wiley and Sons, Second Edition, 1991); and the aryl in arylamino and aryloxy substituents is not further substituted.
[0033] As used herein, the term “arylamino” means, unless otherwise specified, a -NR'R” group, where R' is hydrogen or a C1-C6-alkyl group, and R” is an aryl group as defined herein.
[0034] As used herein, the term "arylene" refers to a divalent aryl group as defined herein, unless otherwise specified.
[0035] As used herein, the term "aryloxy" means, unless otherwise specified, -OR refers to an OR group, where R is an aryl group as defined herein.
[0036] "Alkali-lene" refers to an arylene group as defined herein, in which the aryl ring is substituted with one or two alkyl groups. "Substituted alkali-lene" refers to an alkali-lene as defined herein, in which the arylene group is further substituted, as defined herein for aryl groups.
[0037] "Aralkylene" means an alkyl-arylene- or arylene-alkyl, for example, a C1-C2 alkyl-arylene-, arylene-C1-C2 alkyl-, or a C1-C2 alkyl-arylene-C1-C2 alkyl- group, where arylene is as defined herein. "Substituted alkali-rene" means an aralkylene as defined herein, in which the aralkylene group is substituted as defined herein for aryl. "Substituted C1-C2 alkyl" means a C1-C2 alkyl group that is substituted as defined herein for alkyl.
[0038] "Arylalkylene" means an alkyl-arylene- or arylene-alkyl, for example, a C1-C2 alkyl-arylene-, arylene-C1-C2 alkyl-, or a C1-C2 alkyl-arylene-C1-C2 alkyl- group, where arylene is as defined herein. "Substituted arylalkylene" means an arylalkylene as defined herein, in which an arylalkylene group is substituted as defined herein for aryl. "Substituted C1-C2 alkyl" means a C1-C2 alkyl group that is substituted as defined herein for alkyl.
[0039] "Carboxyl" or "carboxy" refers to -C(O)OH or -COOH.
[0040] The term "cycloalkyl," as used herein, refers to a saturated cyclic hydrocarbon unless otherwise specified. In certain embodiments, a cycloalkyl group may be saturated, and / or crosslinked, and / or uncrosslinked, and / or condensed bicyclic group. In certain embodiments, a cycloalkyl group may contain 3 to 10 carbon atoms (i.e., C3 to C3). 10 Cycloalkyl). In some embodiments, the cycloalkyl has 3 to 15 carbon atoms (C 3~15 ), 3 to 10 carbon atoms (C 3~10 ), 3-7 carbon atoms (C 3~7 ), or having 3 to 6 carbon atoms (C3-C6) (i.e., "lower cycloalkyl"). In certain embodiments, the cycloalkyl group is cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexylmethyl, cycloheptyl, bicyclo[2.1.1]hexyl, bicyclo[2.2.1]heptyl, dekalinyl, or adamantyl.
[0041] As used herein, the term “cycloalkylene” refers to a divalent cycloalkyl group as defined herein. In certain embodiments, the cycloalkylene group is [ka] These are examples. Lower cycloalkylenes refer to C3-C6-cycloalkylenes.
[0042] As used herein, the term "cycloalkylalkyl" refers, unless otherwise specified, to an alkyl group as defined herein, substituted with one or two cycloalkyl groups as defined herein.
[0043] As used herein, the term "ester" refers to -C(O)OR or -COOR, where R is an alkyl group as defined herein.
[0044] The term "haloalkyl" refers to an alkyl group as defined herein, which is substituted with one or more independently selected halogen atoms (e.g., one, two, three, four, or five in some embodiments).
[0045] The term "heteroalkyl" refers to an alkyl group as defined herein, in which one or more carbon atoms are substituted by heteroatoms. As used herein, "heteroalkenyl" refers to an alkenyl as defined herein, in which one or more carbon atoms are substituted by heteroatoms. As used herein, "heteroalkynyl" refers to an alkynyl as defined herein, in which one or more carbon atoms are substituted by heteroatoms. Suitable heteroatoms include, but are not limited to, nitrogen (N), oxygen (O), and sulfur (S) atoms. Heteroalkyl groups, heteroalkenyl groups, and heteroalkynyl groups are optionally substituted. Examples of heteroalkyl groups include, but are not limited to, aminoalkyl groups, sulfonylalkyl groups, and sulfinylalkyl groups. Examples of heteroalkyl groups also include, but are not limited to, methylamino groups, methylsulfonyl groups, and methylsulfinyl groups. A "substituted heteroalkyl" refers to a heteroalkyl group substituted with one, two, or three groups independently selected from halogens (e.g., fluoro(F), chloro(Cl), bromo(Br), or iodo(I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, and alkoxy groups. In some embodiments, the heteroalkyl group may contain one, two, three, or four heteroatoms. Those skilled in the art will recognize that a four-membered heteroalkyl group generally contains one or two heteroatoms, a five- or six-membered heteroalkyl group generally contains one, two, or three heteroatoms, and a seven- to ten-membered heteroalkyl group may generally contain one, two, three, or four heteroatoms.
[0046] As used herein, the term “heteroalkylene” refers to a divalent heteroalkyl as defined herein. “Substituted heteroalkylene” refers to a divalent heteroalkyl as defined herein, which has been substituted as described for heteroalkyl.
[0047] The term "heterocycloalkyl" refers to a monovalent, monocyclic, or polycyclic non-aromatic ring system, where one or more ring atoms are heteroatoms independently selected from oxygen (O), sulfur (S), and nitrogen (N) (for example, the nitrogen or sulfur atom may be optionally oxidized, or the nitrogen atom may be optionally quaternized), and the remaining ring atoms of the non-aromatic ring are carbon atoms. In certain embodiments, a heterocycloalkyl is a monovalent, monocyclic, or polycyclic fully saturated ring system. In certain embodiments, a heterocycloalkyl has 3-20, 3-15, 3-10, 3-8, 4-7, 4-11, or 5-6 ring atoms. A heterocycloalkyl can be bonded to a core structure with any heteroatom or carbon atom, resulting in the formation of a stable compound. In certain embodiments, the heterocycloalkyl is a monocyclic, bicyclic, tricyclic, or tetracyclic ring system, and may include condensed or bridging ring systems, and the nitrogen or sulfur atom may be optionally oxidized, and / or the nitrogen atom may be optionally quaternized. In some embodiments, heterocycloalkyl radicals include, but are not limited to, 2,5-diazabicyclo[2.2.2]octanyl, decahydroisoquinolinyl, dihydrobenzisoxazinyl, dihydrofuryl, dihydroisoindolyl, dihydropyranyl, dihydropyrazolyl, dihydropyradinyl, dihydropyridinyl, dihydropyrimidinyl, dihydropyrrolyl, dioxolanyl, 1,4-dithianyl, furanolyl, imidazolidinyl, imidazolinyl, indolinyl, isothiazoly Examples include dinyl, isoxazolidinyl, morpholinyl, octahydroindolyl, octahydroisoindolyl, oxazolidinyl, oxazolidinyl, oxylanyl, piperazinyl, piperidinyl, 4-piperidonyl, pyrazolidinyl, pyrazolinyl, pyrrolidinyl, pyrrolidinyl, quinuclidinyl, tetrahydrofuryl, tetrahydroisoquinolinyl, tetrahydropyranyl, tetrahydrothienyl, thiamorpholinyl, thiazolidinyl, tetrahydroquinolinyl, and 1,3,5-trithianyl. In certain embodiments, heterocycloalkyls may also be optionally substituted as described herein.In certain embodiments, the heterocycloalkyl group is substituted with one, two, or three groups independently selected from halogens (e.g., fluoro(F), chloro(Cl), bromo(Br), or iodo(I)), alkyl, haloalkyl, hydroxyl, amino, alkylamino, oxo, cyano, and alkoxy. In some embodiments, the heterocycloalkyl group may contain one, two, three, or four heteroatoms. Those skilled in the art will recognize that a four-membered heterocycloalkyl group generally contains one or two heteroatoms, a five- or six-membered heterocycloalkyl group generally contains one, two, or three heteroatoms, and a seven- to ten-membered heterocycloalkyl group may generally contain one, two, three, or four heteroatoms.
[0048] "Heterocycloalkylene" refers to a divalent heterocycloalkyl as defined herein.
[0049] The term "heteroaryl" refers to a monovalent monocyclic aromatic group and / or a polycyclic aromatic group, wherein at least one aromatic ring contains one or more heteroatoms independently selected from oxygen, sulfur, and nitrogen. Each ring of a heteroaryl group may contain one or two oxygen atoms, one or two sulfur atoms, and / or one to four nitrogen atoms, provided that the total number of heteroatoms in each ring is four or less and each ring contains at least one carbon atom. In certain embodiments, the heteroaryl has 5 to 20, 5 to 15, or 5 to 10 ring atoms. The heteroaryl may be bonded to the rest of the molecule via nitrogen or carbon atoms. In some embodiments, the monocyclic heteroaryl group may include, but is not limited to, furanyl, imidazolyl, isothiazolyl, isoxazolyl, oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridadinyl, pyridyl, pyrimidinyl, pyrrolyl, triazolyl, thiadiazolyl, thiazolyl, thienyl, tetrazolyl, and triazinyl. Examples of bicyclic heteroaryl groups include, but are not limited to, benzofuranil, benzimidazolyl, benzoisoxazolyl, benzopyranil, benzothiadiazolyl, benzothiazolyl, benzothienyl, benzotriazolyl, benzoxazolyl, phlopyridyl, imidazopyridinyl, imidazothiazolyl, indolidinyl, indazolyl, isobenzofuranil, 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, phenanthridine, phenalsadinyl, phenazinyl, phenothiazinyl, phenoxazinyl, and xanthenyl. In certain embodiments, the heteroaryl may also be optionally substituted as described herein. A "substituted heteroaryl" is a heteroaryl that has been substituted as defined for aryl.
[0050] The term "heteroarylene" refers to a divalent heteroaryl group as defined herein. "Substitutable heteroarylene" is a heteroarylene that is substituted in the manner defined for aryl groups.
[0051] The term "heteroarylalkylene" refers to an alkyl-heteroarylene- or heteroarylene-alkyl group, for example, a C1-C2 alkyl-heteroarylene-, a heteroarylene-C1-C2 alkyl-, or a C1-C2 alkyl-heteroarylene-C1-C2 alkyl- group, where heteroarylene is as defined herein. "Substituted heteroarylalkylene" refers to a heteroarylalkylene as defined herein, wherein the heteroarylalkylene group is substituted, with aryl being as defined herein. "Substituted C1-C2 alkyl" refers to a C1-C2 alkyl group substituted, with alkyl being as defined herein.
[0052] As used herein, "oxo" refers to =O.
[0053] As used herein, the term “protecting group” refers, unless otherwise specified, to a group added to an oxygen, nitrogen, or phosphorus atom to prevent further reaction of that atom or for other purposes. A wide variety of oxygen and nitrogen protecting groups are known to those skilled in the art of organic synthesis. (See, for example, Greene, et al., Protective Groups in Organic Synthesis, John Wiley and Sons, Fourth Edition, 2006, incorporated herein by reference).
[0054] "Pharmacologically acceptable salt" means any salt of a compound provided herein that retains its biological properties, is non-toxic, and is not otherwise undesirable for pharmaceutically acceptable use. Such salts may be derived from a variety of organic and inorganic counterions known in the art.Such salts are not limited to, but include (1) organic or inorganic acids, such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, sulfamic acid, acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, hexanoic acid, cyclopentylpropionic acid, glycolic acid, glutaric acid, pyruvic acid, lactic acid, malonic acid, succinic acid, sorbic acid, ascorbic acid, malic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, 3-(4-hydroxybenzoyl)benzoic acid, picric acid, cinnamic acid, mandelic acid, phthalic acid, lauric acid, methanesulfate Phenol acid, ethanesulfonic acid, 1,2-ethane-disulfonic acid, 2-hydroxyethanesulfonic acid, benzenesulfonic acid, 4-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid, 4-toluenesulfonic acid, camphor acid, camphorsulfonic acid, 4-methylbicyclo[2.2.2]-octa-2-ene-1-carboxylic acid, glucoheptonic acid, 3-phenylpropionic acid, trimethylacetic acid, tert-butylacetic acid, lauryl sulfate, gluconic acid, glutamic acid, hydroxynaphthoic acid, salicylic acid, stearic acid, cyclohexylsulfamic acid Acid addition salts formed with nic acid, quinic acid, muconic acid, etc.; or (2) salts formed when an acidic proton present in the parent compound is replaced by (a) a metal ion, such as an alkali metal ion, an alkaline earth ion, or an aluminum ion, or an alkali metal or alkaline earth metal hydroxide, such as sodium hydroxide, potassium hydroxide, calcium hydroxide, magnesium hydroxide, aluminum hydroxide, lithium hydroxide, zinc hydroxide, and barium hydroxide, or ammonia, or (b) an organic base, such as an aliphatic, alicyclic, or aromatic organic amine, such as, but not limited to, ammonia, methylamine, dimethylamine, diethylamine, picoline, ethanolamine, diethanolamine, triethanolamine, ethylenediamine, lysine, arginine, ornithine, choline, N,N'-dibenzylethylenediamine, chloroprocaine, procaine, N-benzylphenethylamine, N-methylglucaminepiperazine, tris(hydroxymethyl)-aminomethane, tetramethylammonium hydroxide, etc.
[0055] Pharmaceutically acceptable salts include, but are not limited to, sodium, potassium, calcium, magnesium, ammonium, and tetraalkylammonium salts, and, if the compound contains a basic functional group, salts of non-toxic organic or inorganic acids, such as hydrohalides, hydrochlorides, and hydrobroms, sulfates, phosphates, sulfamates, nitrates, acetates, trifluoroacetates, trichloroacetates, propions, hexanoates, cyclopentylpropions, glycolates, glutarates, pyruvates, lactates, malons, succinates, sorbates, ascorbicates, malates, maleates, fumarates, tartrates, citrates, benzoates, and 3-(4-hydroxybenzoyl)benzoates. Examples include salts, picrates, cinnamates, mandelates, phthalates, laurates, methanesulfonates (mesylates), ethanesulfonates, 1,2-ethane-disulfonates, 2-hydroxyethanesulfonates, benzenesulfonates (besilates), 4-chlorobenzenesulfonates, 2-naphthalenesulfonates, 4-toluenesulfonates, camphorates, camphorsulfonates, 4-methylbicyclo[2.2.2]-octa-2-ene-1-carboxylates, glucoheptonates, 3-phenylpropionates, trimethylacetates, tert-butylacetates, lauryl sulfates, glucons, glutamates, hydroxynaphthoates, salicylates, stearates, cyclohexylsulfamates, quinates, and muconates.
[0056] With respect to a composition, the terms “substantially absent” or “substantially absent” refer to a composition containing at least 85% or 90% by weight, 95% or 98% by weight, 99% or 100% by weight in a particular embodiment; or, in a particular embodiment, 95% or 98% or 99% or 100% of a designated enantiomer or diastereomer of the compound. In a particular embodiment, in the methods and compounds provided herein, the compound is substantially absent from one of the two enantiomers. In a particular embodiment, in the methods and compounds provided herein, the compound is substantially absent from one of the two diastereomers. In a particular embodiment, in the methods and compounds provided herein, the compound is substantially absent from the enantiomer (i.e., a racemate or a 50:50 mixture of the compound).
[0057] Similarly, the term “isolated” in relation to a composition refers to a composition comprising at least 85% by weight, 90% by weight, 95% by weight, 98% by weight, or 99% to 100% by weight of the compound, with the remainder comprising other chemical species, enantiomers, or diastereomers.
[0058] "Solvate" refers to a compound or salt thereof provided herein that further contains a solvent bonded by non-covalent intermolecular forces in a stoichiometric or non-stoichiometric amount. When the solvent is water, the solvate is a hydrate.
[0059] "Isotope composition" refers to the amount of each isotope present for a given atom, while "natural isotope composition" refers to the naturally occurring isotope composition or abundance for a given atom. Atoms containing a natural isotope composition may also be referred to as "unenriched" atoms in this specification. Unless otherwise specified, atoms of compounds described herein represent any stable isotope of that atom. For example, unless otherwise specified, if a position is specifically designated as hydrogen (H), that position is understood to have hydrogen in its natural isotope composition.
[0060] "Isotope enrichment" refers to the proportion of a particular isotope incorporated at a given atom within a molecule, instead of its naturally occurring isotope. For example, a deuterium (D) enrichment of 1% at a given position means that 1% of the molecules in a given sample contain deuterium at that particular position. Since the naturally occurring distribution of deuterium is approximately 0.0156%, the deuterium enrichment at any position of a compound synthesized using unenriched starting materials is approximately 0.0156%. The isotope enrichment of the compounds provided herein can be determined using conventional analytical methods known to those skilled in the art, including mass spectrometry and nuclear magnetic resonance spectroscopy.
[0061] "Isotope-enriched" refers to an atom that has an isotopic composition other than that of its natural isotope composition. "Isotope-enriched" may also refer to a compound containing at least one atom that has an isotopic composition other than that of its natural isotope composition.
[0062] As used herein, the "alkyl," "alkylene," "alkylamino," "dialkylamino," "cycloalkyl," "aryl," "arylene," "alkoxy," "amino," "carboxyl," "heterocycloalkyl," "heteroaryl," "heteroarylene," "carboxyl," and "amino acid" groups optionally contain deuterium (D) at one or more positions where a hydrogen (H) atom is present, and the deuterium composition of that atom(s) is different from the natural isotopic composition.
[0063] Furthermore, as used herein, the "alkyl," "alkylene," "alkylamino," "dialkylamino," "cycloalkyl," "aryl," "arylene," "alkoxy," "amino," "carboxyl," "heterocycloalkyl," "heteroaryl," "heteroarylene," "carboxyl," and "amino acid" groups may optionally be carbon-13 in amounts other than those in the natural isotopic composition. 13 Includes C).
[0064] When used herein, "EC 50The term "dose-dependent response" refers to the dose, concentration, or amount of a particular test compound that elicits a dose-dependent response at 50% of the maximum expression of a particular response induced, triggered, or enhanced by that particular test compound.
[0065] When used herein, unless otherwise specified, "IC" refers to the term "IC" 50 The term "maximum response" refers to the amount, concentration, or dose of a specific test compound that achieves 50% inhibition of the maximum response in an assay measuring the maximum response.
[0066] As used herein, the terms “subject” and “patient” are interchangeable. The terms “subject (singular)” and “subject (plural)” refer to animals, mammals including non-primates (e.g., cattle, pigs, horses, cats, dogs, rats, and mice) and primates (e.g., monkeys such as crab-eating macaques, chimpanzees, and humans), and, in certain embodiments, humans. In certain embodiments, the subject is livestock (e.g., horses, cattle, pigs, etc.) or pets (e.g., dogs or cats). In certain embodiments, the subject is humans.
[0067] As used herein, the term “therapeutic agent” refers to any agent(s) that can be used to treat or prevent a disorder or one or more symptoms thereof. In certain embodiments, the term “therapeutic agent” includes compounds provided herein. In certain embodiments, a therapeutic agent is an agent that is known, has been used, or is currently used to treat or prevent a disorder or one or more symptoms thereof.
[0068] "Therapeutic dose" means the amount of compound or composition that, when administered to a subject to treat a condition, is sufficient to produce the effect of such treatment for that condition. The therapeutic dose may vary depending, among other things, on the compound, the disease or disorder and its severity, as well as the age, weight, etc. of the subject being treated.
[0069] In certain embodiments, “treating” or “treatment” of any disease or disorder means improving the disease or disorder present in the subject. In other embodiments, “treating” or “treatment” includes improving at least one physical parameter of the subject that may be difficult to distinguish. In yet another embodiment, “treating” or “treatment” includes modulating the disease or disorder either physically (e.g., stabilizing identifiable symptoms) or physiologically (e.g., stabilizing physiological parameters), or both. In yet another embodiment, “treating” or “treatment” includes delaying or preventing the onset of the disease or disorder, or delaying or preventing the recurrence of the disease or disorder. In yet another embodiment, “treating” or “treatment” includes reducing or eliminating any of the disease or disorder, or delaying the progression of the disease or disorder, or the progression of one or more symptoms of the disease or disorder, or the severity of the disease or disorder, or the severity of one or more symptoms of the disease or disorder.
[0070] As used herein, the term “preventive agent” refers to any agent(s) that can be used to prevent a disorder or one or more symptoms thereof. In certain embodiments, the term “preventive agent” includes the compounds provided herein. In certain other embodiments, the term “preventive agent” does not refer to the compounds provided herein. For example, a preventive agent is an agent that is known to be useful in preventing or interfering with the onset, onset, progression, and / or severity of a disorder, or that has been used or is currently used to halt the onset, onset, progression, and / or severity of a disorder.
[0071] As used herein, the term “preventive effective dose” means an amount of treatment (e.g., a prophylactic agent) sufficient to prevent or reduce the onset, recurrence, or onset of one or more symptoms associated with a disorder, or to enhance or improve the preventive effect of another treatment (e.g., another prophylactic agent). Compounds of formulas (I)-(XVIII), (XXV)-(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII)
[0072] This specification provides GLP-1 receptor compounds useful for modulating one or more properties of the GLP-1 receptor. These compounds may be prepared as described herein and used for treatment or diagnosis. In certain embodiments, the treatment is the treatment of a metabolic disease or metabolic condition. In certain embodiments, the treatment is the treatment of type 2 diabetes.
[0073] The embodiments described herein include the listed compounds, as well as pharmaceutically acceptable salts, hydrates, solvates, stereoisomers, tautomers, and / or mixtures thereof.
[0074] In certain embodiments, compounds of formula (I), or pharmaceutically acceptable salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided; where A is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted cycloalkyl, -NMe2, or -CF3; ring B is a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; ring C is further unsubstituted, further substituted, and / or crosslinked; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 L 1 The group is selected from the group consisting of bonds, -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; L 4 It does not exist, or L 4 is L 1 Furthermore, together with rings A and B, they form a condensed triring, and L 5 It does not exist; and L 5 It does not exist, or L 5 is L 2 Furthermore, together with rings B and C, they form a condensed triring, and L 4 It does not exist; R 4 R is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 6 These are alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, and R 11 R 12 NCO- and R 11 R 12 Independently selected from the group consisting of N-; R 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; and R 13 is hydrogen or alkyl. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The group is selected from the group consisting of -NH- and -N(Me)-.
[0075] In a particular embodiment of formula (I), L 1 is -CH2O-, L 4 L does not exist, 5 If it does not exist, L 2 These are -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, CHF-, -CHOH-, -NH-, -N(Me)-, or [ka] is or L 3 is either -C(O)- or both. In certain embodiments, L 1 is -CH2O-, L 4 L does not exist, 5 If it does not exist, L 2 These are -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, or [ka] In a particular embodiment, L 1 is -CH2O-, L 4 If it does not exist, and L 5 If it does not exist, L 3 is -C(O)-. In certain embodiments, L 1 If it is -CH2O-, then L 4 L 1 Furthermore, together with rings A and B, it forms a condensed triring. In a particular embodiment, L 1 However, if it is -CH2O-, L 5 L 2 Furthermore, together with rings B and C, it forms a condensed triring. In a particular embodiment, L 1However, if it is -CH2O-, the ring C is a substituted or unsubstituted azetidinyl, a substituted or unsubstituted pyrrolidinyl, or a substituted or unsubstituted piperidinyl.
[0076] In certain embodiments, A is a ring selected from phenyl and cyclohexyl. In certain embodiments, ring C is selected from piperidine and piperazine. In certain embodiments, ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran. In certain embodiments, A is phenyl and ring C is piperazine. In certain embodiments, A is phenyl and ring C is piperidine. In certain embodiments, A is phenyl and ring C is piperazine and ring B is phenyl. In certain embodiments, A is phenyl and ring C is piperazine and ring B is furan. In certain embodiments, A is phenyl and ring C is piperidine and ring B is phenyl. In certain embodiments, A is phenyl and ring C is piperidine and ring B is furan.
[0077] In certain embodiments, A is a ring selected from phenyl and cyclohexyl. In certain embodiments, ring C is selected from substituted piperidine, azetidine, and pyrrolidine. In certain embodiments, ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran. In certain embodiments, A is phenyl and ring C is piperazine. In certain embodiments, A is phenyl and ring C is piperidine. In certain embodiments, A is phenyl and ring C is substituted piperidine. In certain embodiments, A is phenyl and ring C is azetidine. In certain embodiments, A is phenyl and ring C is pyrrolidine. In certain embodiments, A is phenyl, ring C is piperazine, and ring B is phenyl. In certain embodiments, A is phenyl, ring C is piperazine, and ring B is furan. In certain embodiments, A is phenyl, ring C is piperidine, and ring B is phenyl. In certain embodiments, A is phenyl, ring C is piperidine, and ring B is furan. In certain embodiments, A is phenyl, ring C is substituted piperidine, and ring B is phenyl. In certain embodiments, A is phenyl, ring C is substituted piperidine, and ring B is furan. In certain embodiments, A is phenyl, ring C is azetidine, and ring B is phenyl. In certain embodiments, A is phenyl, ring C is azetidine, and ring B is furan. In certain embodiments, A is phenyl, ring C is pyrrolidine, and ring B is phenyl. In certain embodiments, A is phenyl, ring C is pyrrolidine, and ring B is furan.
[0078] In certain embodiments, compounds of formula (Ia), or pharmaceutically acceptable salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided; where A is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted cycloalkyl, -NMe2, or -CF3; ring B is a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; ring C is further unsubstituted, further substituted, and / or crosslinked; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 And; W is N, CH, or C; if W is CH, adjacent dashed lines indicate single bonds; if W is C, adjacent dashed lines indicate double bonds, for example, L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; L 4 It does not exist, or L 4 is L 1 Furthermore, together with rings A and B, they form a condensed triring, and L 5 It does not exist; L 5 It does not exist, or L 5 is L 2 Furthermore, together with rings B and C, they form a condensed triring, and L 4 It does not exist; R 4R is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 6 These are alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, and R 11 R 12 NCO- and R 11 R 12 Independently selected from the group consisting of N-; R 11 R is hydrogen or alkyl; 12 R is hydrogen or alkyl; 13 is hydrogen or alkyl. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The group is selected from the group consisting of -NH- and -N(Me)-.
[0079] In a particular embodiment of formula (Ia), L 1 is -CH2O-, L 4 If it does not exist, and L 5 If it does not exist, L 2These are -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, or [ka] is or L 3 is either -C(O)- or both. In certain embodiments, L 1 However, it is -CH2O- and L 4 If it does not exist, and L 5 If it does not exist, L 2 These are -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, or [ka] In a particular embodiment, L 1 is -CH2O-, L 4 If it does not exist, and L 5 If it does not exist, L 2 These are -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, or [ka] In a particular embodiment, L 1 is -CH2O-, L 4 If it does not exist, and L 5 If it does not exist, L 3 is -C(O)-. In certain embodiments, L 1 If it is -CH2O-, then L 4 L 1 Furthermore, together with rings A and B, it forms a condensed triring. In a particular embodiment, L 1 However, if it is -CH2O-, L 5 is L 2 Furthermore, together with rings B and C, they form a condensed triring.
[0080] In certain embodiments, A is a ring selected from phenyl and cyclohexyl. In certain embodiments, ring C is selected from piperidine and piperazine. In certain embodiments, ring B is selected from phenyl, furan, pyridine, pyrimidine, thiophene, oxazole, and benzofuran. In certain embodiments, A is phenyl and ring C is piperazine. In certain embodiments, A is phenyl and ring C is piperidine. In certain embodiments, A is phenyl and ring C is piperazine and ring B is phenyl. In certain embodiments, A is phenyl and ring C is piperazine and ring B is furan. In certain embodiments, A is phenyl and ring C is piperidine and ring B is phenyl. In certain embodiments, A is phenyl and ring C is piperidine and ring B is furan.
[0081] In certain embodiments, compounds of formula (XXX), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided; where W is N, CH, or C; where W is CH, adjacent dashed lines indicate single bonds; where W is C, adjacent dashed lines indicate double bonds, for example, L 2 -C(H)= and A 1 , A 2 , A 3 , A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 1 B 1 B 2 B 3 , and B 4 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 2 And; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 L 1It is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is an unsubstituted alkyl, substituted alkyl, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 6 These are alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, and R 11 R 12NCO- and R 11 R 12 Independently selected from the group consisting of N-; R 11 R is hydrogen or alkyl; 12 R is hydrogen or alkyl; 13 is hydrogen or alkyl; and o is an integer from 0 to 4. In certain embodiments, the compound of formula (XXX) is selected from compounds 82, 83, 91, 92, and 110 in Table 1.
[0082] In certain embodiments, compounds of formula (XXXI), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided; where W is N, CH, or C; where W is CH, adjacent dashed lines indicate a single; A 1 , A 2 , A 3 , A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 1 That is the case. D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 and; Each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; L 1 It is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L3 is -CH2- or -C(O)-; Each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 This includes unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; R 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; Each R 6 It is independently selected from the group consisting of F and methyl; R 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; R 13 is hydrogen or alkyl; and o is 1, 2, 3, or 4. In certain embodiments, the compound of formula (XXXI) is selected from compounds 97 and 107 in Table 1.
[0083] In certain embodiments, the compound of formula (I) is derived from formula (IIa), or a pharmaceutically acceptable salt thereof, tautomer, stereoisomer, and / or mixture of stereoisomers: [ka] Here, A 1 , A 2 , A 3 , A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 1 B 1 B 2 B 3 , and B 4 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 2 And in the formula, formula IIaB 4 It does not exist; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 and; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and independently selected from the group consisting of tetrazolyl; each R 6 is independently selected from the group consisting of F and methyl; each R 11 R is either hydrogen or alkyl, and each R 12は It is hydrogen or alkyl, and each R 13 is hydrogen or alkyl, and o is 1, 2, 3, or 4.
[0084] In certain embodiments, the compound of formula (I) is obtained by formula (IIb), or by a pharmaceutically acceptable salt thereof, tautomer, stereoisomer, and / or mixture of stereoisomers: [ka] In the formula, A 1 , A 2 , A 3 , A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 1 B 1 B 2 B 3 , and B 4 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 2 And here, in equation IIb, B 4 It does not exist; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 and; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and independently selected from the group consisting of tetrazolyl; each R 6 is independently selected from the group consisting of F and methyl; each R 11 R is either hydrogen or alkyl, and each R 12 R is either hydrogen or alkyl, and each R 13 is hydrogen or alkyl, and o is 1, 2, 3, or 4.
[0085] In certain embodiments, the compound of formula (I) is obtained by formula (IIc), or by a pharmaceutically acceptable salt thereof, tautomer, stereoisomer, and / or mixture of stereoisomers: [ka] In the formula, A 1 , A 2 , A 3 , A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 1 B 1 B 2 B 3 , and B 4Of these, 0, 1, or 2 are N, and the rest are CH or CR. 2 And in equation IIc, B 4 It does not exist; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 and; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and independently selected from the group consisting of tetrazolyl; each R 6 is independently selected from the group consisting of F and methyl; each R 11 R is either hydrogen or alkyl, and each R 12 R is either hydrogen or alkyl, and each R 13 R is hydrogen or alkyl;14 is hydrogen, cyano, halo, hydroxyl, or methyl; and o is 1, 2, 3, or 4.
[0086] In certain embodiments, the compound of formula (I) is derived from formula (IId), or a pharmaceutically acceptable salt thereof, tautomer, stereoisomer, and / or mixture of stereoisomers: [ka] In the formula, A 1 , A 2 , A 3 , A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 1 B 1 B 2 B 3 , and B 4 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 2 And in equation IId, B 4 It does not exist; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 and; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4R is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and independently selected from the group consisting of tetrazolyl; each R 6 is independently selected from the group consisting of F and methyl; each R 11 R is either hydrogen or alkyl, and each R 12 R is either hydrogen or alkyl, and each R 13 R is hydrogen or alkyl; 14 is hydrogen, cyano, halo, hydroxyl, or methyl; and o is 1, 2, 3, or 4.
[0087] In certain embodiments, the compound of formula (I) is obtained by formula (IIg), or by a pharmaceutically acceptable salt thereof, tautomer, stereoisomer, and / or mixture of stereoisomers: [ka] In the formula, A 1 , A 2 , A 3 , A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 1 B 1 B 2 B 3 , and B 4 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 2 And in formula IIg, B4 It does not exist; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 and; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 6 is independently selected from the group consisting of F and methyl; each R 11 R is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 It is hydrogen or alkyl.
[0088] In certain embodiments, the compound of formula (I) is derived from formula (IIh), or a pharmaceutically acceptable salt thereof, tautomer, stereoisomer, and / or mixture of stereoisomers: [ka] In the formula, A 1 , A 2 , A 3 , A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 1 B 1 B 2 B 3 , and B 4 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 2 And in formula IIg, B 4 It does not exist; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR. 6 and; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5-COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 6 is independently selected from the group consisting of F and methyl; each R 11 R is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 It is hydrogen or alkyl.
[0089] In certain embodiments, compounds of formula (III), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] Here, W is N, CR 14 , or C, and W is CR 14 If W is C, adjacent dashed lines indicate a single bond; if W is C, adjacent dashed lines indicate a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -NH-, N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11 R is hydrogen or alkyl; each R 12 R 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 embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2L2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of formula (III) is 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 from Table 1. The numbers are selected from 130-133, 135, 137, 148, 149, 151, 157-159, 161, 162, 165, 166, 174, 187, 188, 202-208, 215-217, 221, 231, 232, 242, 243, 254, 255, 260, 263, 288, 294, 301, 318, 319, and 321.
[0090] In certain embodiments, compounds of formula (IIIa), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11 is hydrogen or alkyl, and each R 12 is hydrogen or alkyl, and each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; o is an integer from 0 to 4. In certain embodiments, L 2 L2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of formula (IIIa) is selected from compounds 103, 104, 111, 116, 126, 130-133, 135, 137, 148, 149, 151, 157-159, 161, 162, 165, 166, 174, 187, 188, 202-208, 215-217, 221, 231, 232, 242, 243, 254, 255, 260, 263, 288, 294, 301, 318, 319, and 321 in Table 1.
[0091] In certain embodiments, compounds of formula (IV), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C, and W is CR 14 If W is C, adjacent dashed lines indicate a single bond; if W is C, adjacent dashed lines indicate a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5-COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11 R is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (IV) is selected from compounds 8, 9, 19, 20, 24, 26, 30, 31, 36-43, 47, 49, 55, 59, 63, 72-74, 81, 84, 94, 96, 108, and 109 in Table 1.
[0092] In certain embodiments, compounds of formula (V), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] Here, W is N, CR 14 , or C; W is CR 14 If W is C, adjacent dashed lines indicate a single bond; if W is C, adjacent dashed lines indicate a double bond or L 2 -C(H)= and L 1The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11R is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer from 0 to 5; m is an integer from 0 to 4; and o is an integer from 0 to 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (V) is selected from the 71 compounds in Table 1.
[0093] In certain embodiments, compounds of formula (VI), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is selected from the group consisting of -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of 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 between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (VI) is selected from compounds 34, 62, and 331 in Table 1.
[0094] In certain embodiments, compounds of formula (VII), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is selected from the group consisting of -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of 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 between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (VII) is selected from compounds 60, 102, 113, 124, 136, 138, 141, 144, 154, 156, 160, 186, 214, 256, 278, and 279 in Table 1.
[0095] In certain embodiments, compounds of formula (VIII), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and independently selected from the group consisting of tetrazolyl; each R 11 R is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (VIII) is selected from compound 44 in Table 1.
[0096] In certain embodiments, compounds of formula (IX), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is independently selected from the group consisting of alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] and independently selected from the group consisting of 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 between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (IX) is selected from compounds 27 and 28 in Table 1.
[0097] In certain embodiments, a compound of formula (X), or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, and / or a mixture of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is independently selected from the group consisting of alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Independently selected from the group consisting of 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 between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (X) is selected from compounds 4, 272, and 284 in Table 1.
[0098] In certain embodiments, compounds of formula (XI), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11 R is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (XI) is selected from compounds 53, 90, 121, 142, and 143 in Table 1.
[0099] In certain embodiments, compounds of formula (XII), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11 R is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (XII) is compound 108 in Table 1.
[0100] In certain embodiments, compounds of formula (XIII), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11 R is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (XIII) is selected from compounds 88, 178, and 179 in Table 1.
[0101] In certain embodiments, compounds of formula (XIV), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5-COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11 R is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (XIV) is selected from compounds 85, 139, and 220 in Table 1.
[0102] In certain embodiments, compounds of formula (XV), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 1The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11R is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 L2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of formula (XV) is selected from compounds 101, 114, 118, 120, 123, 140, 146, 152, 153, 198-200, 246-249, 251-253, 264, 268-271, 285, 290, 291, 330, and 347 in Table 1.
[0103] In certain embodiments, compounds of formula (XVI), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11 R is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 L2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, R 14 is CH2F or CH2OH. In certain embodiments, the compound of formula (XVI) is selected from compounds 99, 128, 145, 150, 155, 163, 164, 168-171, 182, 183, 189, 227, 230, 239-241, 250, 257-259, 265-267, 274-277, 280, 283, 287, 292, 295, 297, 299, 308, 316, 321, 322, 333, 335, 337, 345, 346, 352, 354, 356-358, 362-364, 366-368, 378, and 380 in Table 1.
[0104] In certain embodiments, compounds of formula (XVIa), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka]
[0105] In the formula, L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is selected from the group consisting of -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 R is hydrogen or alkyl; 14 L 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 embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2L2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of formula (XVI) is selected from compounds 128, 145, 168-171, 182, 183, 227, 230, 239-241, 250, 257-259, 265-267, 274-277, 280, 283, 287, 292, 295, 297, 299, 302, 308, 316, 321, 322, 333, 335-337, 344-346, 352, 354, 356-359, 362-368, 378, and 380 in Table 1.
[0106] In certain embodiments, compounds of formula (XVII), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11 is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (XVII) is selected from compound 106 in Table 1.
[0107] In certain embodiments, compounds of formula (XVIII), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka]
[0108] In the formula, W is N, CR 14, or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is independently selected from the group consisting of alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5-COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of 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 between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (XVIII) is compound 87 in Table 1.
[0109] In certain embodiments, compounds of formula (XXV), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, W is N, CR 14 , or C, and W is CR 14 If W is C, adjacent dashed lines indicate a single bond; if W is C, adjacent dashed lines indicate a double bond, or L 2 -C(H)= and L 1The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 11 R is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 R is hydrogen or alkyl; 14is 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 of 0 or 1; q is an integer of 0 or 1. In certain embodiments, p is 0 and q is 0. In certain embodiments, p is 1 and q is 0. In certain embodiments, p is 0 and q is 1. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -CF2-, -SO2-, -O-, -CF2-, -CHF-, -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 The compound is selected from the group consisting of -NH- and -N(Me)-. In a particular embodiment, the compound of formula (XXV) is compound 286 in Table 1.
[0110] In certain embodiments, compounds of formula (XXVI), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka]
[0111] In the formula, W is N, CR 14 , or C; W is CR 14 If W is C, this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [Chemical] selected from the group consisting of; L 3 is -CH2- 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, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [Chemical] 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 of 0 to 5; m is an integer of 0 to 4; and o is an integer of 0 to 4. In certain embodiments, L 2These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 L2 is selected from the group consisting of -NH- and -N(Me)-. In certain embodiments, L2 is O. In certain embodiments, the compound of formula (XXVI) is selected from compounds 261, 262, 296, 304, 306, 307, 311, 313, 315, 325, 326, 331, 338, 340, 342, 343, 348, 353, 354, 355, 369, 374~, 376, 475~481, 483, 485, 489, 490, 492, 493, 495, 498, 504, 510, 512, 514, and 515 in Table 1.
[0112] In certain embodiments, compounds of formula (XXVII), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, A is -NMe2 or -N(CH3)cyclohexane; L 1 It does not exist; W is N, CR 14 , or C; W is CR 14 And this adjacent dashed line indicates a single bond; if W is C, this adjacent dashed line indicates a double bond or L 2 -C(H)= and L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is selected from the group consisting of -CH2- or -C(O)-; each R 1These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of 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 between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] The compound is selected from the group consisting of the following. In a particular embodiment, the compound of formula (XXVII) is selected from compounds 1 and 62 in Table 1.
[0113] In certain embodiments, compounds of formula (XXXIX), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl;5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 6 These are alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, and R 11 R 12 NCO- and R 11 R 12 Independently selected from the group consisting of N-; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 L is hydrogen or alkyl; n is an integer between 0 and 5; m is an integer between 0 and 4; o is an integer between 0 and 4; and r is an integer between 0 and 3. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, each R 6 is independently selected from the group consisting of F and methyl. In a particular embodiment, each R 6 is F. In a particular embodiment, the compound of formula (XXXIX) is selected from compounds 224, 300, 303, 309, 310, 317, and 320 in Table 1.
[0114] In certain embodiments, compounds of formula (XL), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R6 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 embodiments, L 2 is selected from the group consisting of a bond, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and
化
[0115] In certain embodiments, provided is a compound of formula (XLI), or a pharmaceutical salt, tautomer, stereoisomer, and / or mixture of stereoisomers thereof:
化
化
[0116] In certain embodiments, compounds of formula (XLII), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of 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 between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2is -O-. In a particular embodiment, the compound of formula (XLII) is selected from compounds 370, 371, 373, 375, 377, 378, 486, and 513 in Table 1.
[0117] In certain embodiments, compounds of formula (XLIII), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylene; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 6 These are alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, and R 11 R 12 NCO- and R 11 R 12 Independently selected from the group consisting of N-; each R 11 R is hydrogen or alkyl; each R 12 R is hydrogen or alkyl; each R 13 is hydrogen or alkyl; n is an integer between 0 and 5; m is an integer between 0 and 4; o is an integer between 0 and 4; and r is an integer between 0 and 3. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 is -O-. In a particular embodiment, each R 6 is independently selected from the group consisting of F and methyl. In a particular embodiment, each R 6 is F. In a particular embodiment, each R 6is methyl. In certain embodiments, the compound of formula (XLIII) is selected from compounds 487 and 488 in Table 1.
[0118] In certain embodiments, compounds of formula (XLII), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl;5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of 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 between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 It is -O-. In a particular embodiment, the compound of formula (XLIV) is compound 372 in Table 1.
[0119] In certain embodiments, compounds of formula (XLV), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of 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 between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 It is -O-. In a particular embodiment, the compound of formula (XLV) is compound 379 in Table 1.
[0120] In certain embodiments, compounds of formula (XLVI), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, L 1 The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of 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 between 0 and 5; m is an integer between 0 and 4; and o is an integer between 0 and 4. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, L 2 is -O-. In certain embodiments, the compound of formula (XLVI) is selected from compounds 125 and 129 in Table 1.
[0121] In certain embodiments, compounds of formula (XLI), or pharmaceutically active salts thereof, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided: [ka] In the formula, L 1The group is selected from the group consisting of -O-, -CH2-, -NH-, -N(Me)-, -N(Et)-, -OCH2-, -OC(H,Me)-, -CH2O-, -NHCH2-, -N(Me)CH2-, and -SO2NH-; L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -NH-, -N(Me)-, and [ka] Selected from the group consisting of; L 3 is -CH2- or -C(O)-; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 R is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkyl, or substituted heterocycloalkyl; 5 -COOH, -COCF3, -C(OH)CF3, -CONHCN, -CONHOH, CONHOMe, -CONHSO2N(Me)2, -PO3H2, -PO(Me)(OH), -SO3H, -SO2NH2, -SO2NHMe, -B(OH)2, [ka] Selected from the group consisting of and tetrazolyl; each R 6These are alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, and R 11 R 12 NCO- and R 11 R 12 Independently selected from the group consisting of N-; each R 11 is hydrogen or alkyl; each R 12 is hydrogen or alkyl; each R 13 L is hydrogen or alkyl; n is an integer between 0 and 5; m is an integer between 0 and 4; o is an integer between 0 and 4; and r is an integer between 0 and 3. In certain embodiments, L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-, and [ka] Selected from the group consisting of. In a particular embodiment, each R 6 is independently selected from the group consisting of F and methyl. In a particular embodiment, each R 6 is F. In a particular embodiment, each R 6 is methyl. In a particular embodiment, the compound of formula (XLVII) is compound 491 in Table 1.
[0122] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, each R 2 and R 3 It is either H or F.
[0123] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where m is 0 and o is 0.
[0124] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers, where W is N or CH.
[0125] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers, where W is C.
[0126] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers, where W is CH.
[0127] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers, where W is N.
[0128] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where W is CR. 14 That is the case.
[0129] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, R 4 The selected substance is from the group consisting of oxetan-2-ylmethyl, (1-ethyl-1H-imidazole-5-yl)methyl, oxeran-3-ylmethyl, and 1,3-oxazole-2-ylmethyl.
[0130] In certain embodiments, compounds of any of the formulas (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where R 4 The compound is selected from the group consisting of oxetane-2-ylmethyl and (1-ethyl-1H-imidazole-5-yl)methyl.
[0131] In certain embodiments, compounds of any of the formulas (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where R 4 It is oxetane-2-yl-methyl.
[0132] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where R 4 It is (2S)-oxetane-2-yl-methyl.
[0133] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where R 4 It is (1-ethyl-1H-imidazole-5-yl)methyl.
[0134] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where R 4 The selected compound is from the group consisting of (S)-buta-4-yl-1,3-diol, butan-1-yl-one, 1-(cyanomethyl)-cyclopropa-1-yl-methyl, 1-(fluoromethyl)-cyclopropa-1-yl-methyl, 1-hydroxyl-cyclopropa-1-yl-methyl, isoxazole-5-yl-methyl, (1-methyl-1H-imidazole-5-yl)-methyl, 1-methoxy-cyclopropa-1-yl-methyl, methoxyethane-2-yl, 1-(2-methoxyethyl)-cyclopropa-1-yl-methyl, and 2-oxabicyclo[2.1.1]hexa-1-yl-methyl.
[0135] In certain embodiments, compounds of formula (XXX), or pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures thereof are provided, where R 4 H is H.
[0136] In certain embodiments, a compound of formula (XXX), or a pharmaceutically acceptable salt thereof, a tautomer, a stereoisomer, and / or a mixture of stereoisomers thereof, wherein R 4 The compound is selected from the group consisting of oxeran-3-ylmethyl and 1,3-oxazole-2-ylmethyl.
[0137] In certain embodiments, compounds of formulas (XXX) and (XXXI), or pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures thereof are provided, where R 4 (3R)-oxeran-3-yl-methyl is (3R)-oxeran-3-yl-methyl.
[0138] In certain embodiments, compounds of formulas (XXX) and (XXXI), or pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures thereof are provided, where R 4 It is 1,3-oxazole-2-yl-methyl.
[0139] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where R 5 It is -COOH or -COOMe.
[0140] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where R 5 It is -COOH.
[0141] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where R 5 It is tetrazolyl.
[0142] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where R 5 It is 1H-1,2,3,4-tetrazole-5-yl.
[0143] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 These are -CH2-, -C(O)-, or -SO2-.
[0144] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 These are bonds, -C(O)-, -CH2-, -C(H)=, -SO2-, -O-, -CF2-, -CHF-, or -CH(OH)-.
[0145] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 is -CH= or -O-.
[0146] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2These are -CF2-, -CHF-, or -CH(OH)-.
[0147] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 It is -NH- or -N(Me)-.
[0148] In certain embodiments, compounds of formula (XXX), or pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures thereof are provided, where L 2 It is a combination.
[0149] In certain embodiments, compounds of formula (XXXI), or pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures thereof are provided, where L 2 It is -CH2-.
[0150] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 3 It is -CH2-.
[0151] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 3 It is -C(O)-.
[0152] In certain embodiments, compounds of formula (XXX), or pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures thereof are provided, where L 1It is -CH2O- or -OCH2-.
[0153] In certain embodiments, compounds of formula (XXXI), or pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures thereof are provided, where L 1 It is -CH2O- or -OCH2.
[0154] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 is -CH2O- and L 2 It is either -CH2- or -CO-.
[0155] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 is -CH2O- and L 3 is -C(O)-.
[0156] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 It is -O-.
[0157] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 It is -CH2-.
[0158] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 It is -NH-.
[0159] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 It is -N(Me)-.
[0160] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 It is -N(Et)-.
[0161] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 It is -OCH2-.
[0162] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 This is -OC(H,Me)-.
[0163] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 It is -CH2O-.
[0164] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 It is -NHCH2-.
[0165] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 This is -N(Me)CH2-.
[0166] In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 1 It is -SO2NH-.
[0167] In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -C(O)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O- and L2 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O- and L 2 In any particular embodiment of equations (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O- and L 2 L is -SO2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O- and L 2 L is -NH-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O- and L 2 L is -N(Me)-. In any particular embodiment 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 -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(H)= and L 3is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH- and L 3 is -CH2-. In any particular embodiment 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 -CH2-. In any particular embodiment 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 -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O- and; L 2 is -CH2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O- and; L 2 -C(H)= and L 3 is -CH2- and R2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O- and; L 2 is -SO2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O- and; L 2 is -NH-;L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O- and; L 2 is -N(Me)- and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O- and; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL~XLVII), L 1 is -O-;L 2 It is -CH2- and L 3 is -CH2-;R 2 and R3 Each of them is H, and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O- and; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 It is -COOH. Equations (I)~(XVIII), (XXV)~(X In any particular embodiment of XVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is H, and R is R. 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), L 1 is -O-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -CH2-; L3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 It is -CH2- and L 3 It is -CH2-, and R 2 and R 3 H and R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O- and; L2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -O-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 This is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. The specific formulas are (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII). In this embodiment, L 1 is -O-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any embodiment according to this paragraph, R 1 R can be selected from H, Cl, F, Me, -CF3, -OMe, -CN, -C(O)NMe2, alkyl, propyl, isopropyl, and cyclopropyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), R 4 R is azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3R)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3S)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (S)-buta-4-yl-1,3-diol. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL~XLIIV), R 4 R is butane-1-ylone. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(cyanomethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4R is 1-(fluoromethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-hydroxyl-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazole-5-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (1-methyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-methoxycyclopropa-1-ylmethyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is methoxyethane-2-yl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(2-methoxyethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4R is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 L is -NH-. In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 It is -N(Me)-.
[0168] In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O- and L 2 L is -C(O)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O- and L 2 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O- and L2 In any particular embodiment of equations (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O- and L 2 L is -SO2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O- and L 2 L is -NH-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O- and L 2 L is -N(Me)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -C(O)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), and (XXXI), L 1 It is -CH2O-;L 2 is -CH2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -C(H)= and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -SO2- and L 3is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -NH- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -N(Me)-- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 It is -CH2O-;L 2 is -C(O)-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -CH2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 -C(H)= and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1It is -CH2O-;L 2 is -SO2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -NH-;L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -N(Me)- and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -CH2O-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -CH2O-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L2 is -NH-;L 3 It is -CH2-, and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL~XLVII), L 1 It is -CH2O-;L 2 is -N(Me)- and L 3 is -CH2-, and ;R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL~XLVII), L 1 It is -CH2O-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H and R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is H, and R is R. 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 is -NH-;L 3is -CH2- and R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 is -N(Me)- and L 3 is -CH2- and R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 This is tetrazolyl, for example, 1H-1,2,3,4-tetra It is zole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -CH2O-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any embodiment according to this paragraph, R 1 R can be selected from H, Cl, F, Me, -CF3, -OMe, -CN, -C(O)NMe2, alkyl, propyl, isopropyl, and cyclopropyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), R 4 R is azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3R)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3S)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (S)-buta-4-yl-1,3-diol. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), and (XXXI), R 4 R is butane-1-ylone. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(cyanomethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), R 4 R is 1-(fluoromethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4R is 1-hydroxyl-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazole-5-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (1-methyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), R 4 R is 1-methoxycyclopropa-1-ylmethyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is methoxyethane-2-yl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(2-methoxyethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4This is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain embodiments, compounds of any of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII) or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 L is -NH-. In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 It is -N(Me)-.
[0169] In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2- and L 2 L is -C(O)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2- and L 2 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2- and L 2 In any particular embodiment of equations (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -OCH2- and L 2 L is -SO2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), and (XXXI), L 1 is -OCH2- and L 2 L is -NH-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2- and L 2 L is -N(Me)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -C(O)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -CH2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -C(H)= and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -SO2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L2 is -NH- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -N(Me)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -C(O)-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -CH2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 -C(H)= and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -SO2-; L 3 is -CH2- and R 2 and R 3Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIVII), L 1 is -OCH2-;L 2 is -NH-;L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -OCH2-;L 2 is -N(Me)- and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 -C(H)= and L 3is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 teeth , is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -OCH2-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIVII), L 1 is -OCH2-;L 2is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OCH2-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLIII), L 1 is -OCH2-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 This is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII) , L 1 is -OCH2-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OCH2-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any embodiment according to this paragraph, R1 R can be selected from H, Cl, F, Me, -CF3, -OMe, -CN, -C(O)NMe2, alkyl, propyl, isopropyl, and cyclopropyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), R 4 R is azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3R)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3S)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (S)-buta-4-yl-1,3-diol. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is butane-1-ylone. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), R 4 R is 1-(cyanomethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), R 4 R is 1-(fluoromethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), R 4R is 1-hydroxyl-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazole-5-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), R 4 R is (1-methyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-methoxycyclopropa-1-ylmethyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is methoxyethane-2-yl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(2-methoxyethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4This is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain embodiments, compounds of any of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 L is -NH-. In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 It is -N(Me)-.
[0170] In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH- and L 2 L is -C(O)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH- and L 2 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), and (XXXI), L 1 is -NH- and L 2 In any particular embodiment of equations (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH- and L 2L is -SO2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH- and L 2 L is -NH-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH- and L 2 L is -N(Me)-. In any particular embodiment 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 -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -CH2- and L 3 is -CH2-. In any particular embodiment 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 -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -SO2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2is -NH- and L 3 is -CH2-. In any particular embodiment 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 -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL~XLVII), L 1 is -NH-;L 2 is -C(O)- and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -CH2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 -C(H)= and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -SO2-; L 3 is -CH2- and R 2 and R 3Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -NH-;L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment 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 -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 -C(H)= and L 3 is -CH2-;R2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment 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 -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 It is (2S)-oxetane-2-yl-methyl ; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment 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 -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -NH-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -NH-;L 3is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment 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 -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -CH2-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 It is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -NH-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any embodiment according to this paragraph, R 1R can be selected from H, Cl, F, Me, -CF3, -OMe, -CN, -C(O)NMe2, alkyl, propyl, isopropyl, and cyclopropyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), R 4 R is azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3R)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3S)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (S)-buta-4-yl-1,3-diol. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is butane-1-ylone. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 , is 1-(cyanomethyl)-cyclopropa-1-ylmethyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R4 is 1-(fluoromethyl)-cyclopropa-1-ylmethyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4R is 1-hydroxyl-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazole-5-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (1-methyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-methoxycyclopropa-1-ylmethyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is methoxyethane-2-yl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(2-methoxyethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4This is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain embodiments, compounds of any of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 L is -NH-. In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 It is -N(Me)-.
[0171] In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 L is -C(O)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 L is -SO2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -N(Me)- and L 2 L is -NH-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 L is -N(Me)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -C(O)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -CH2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -C(H)= and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -SO2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -NH- and L 3is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -N(Me)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -C(O)-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -CH2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 -C(H)= and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -SO2-; L 3 is -CH2- and R 2 and R 3Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -N(Me)- and L 2 is -NH-;L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -N(Me)- and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 -C(H)= and L 3is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -N(Me)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XVII), L 1 is -N(Me)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -C(O)-; L 3 is -CH2-;R 2and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), L 1 is -N(Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Me)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any embodiment according to this paragraph, R1 R can be selected from H, Cl, F, Me, -CF3, -OMe, -CN, -C(O)NMe2, alkyl, propyl, isopropyl, and cyclopropyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), R 4 R is azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3R)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3S)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (S)-buta-4-yl-1,3-diol. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is butane-1-ylone. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(cyanomethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(fluoromethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4R is 1-hydroxyl-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazole-5-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (1-methyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-methoxycyclopropa-1-ylmethyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is methoxyethane-2-yl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(2-methoxyethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4This is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain embodiments, compounds of any of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 L is -NH-. In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 It is -N(Me)-.
[0172] In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 L is -C(O)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 In any particular embodiment of equations (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -N(Et)- and L 2 L is -SO2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 L is -NH-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 L is -N(Me)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -C(O)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -CH2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -C(H)= and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -SO2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 is -N(Et)- and L 2 is -NH- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -N(Me)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -C(O)-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -CH2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 -C(H)= and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -SO2-; L 3 is -CH2- and R 2 and R 3Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -NH-;L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -N(Me)- and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 -C(H)= and L 3is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIVI), L 1 is -N(Et)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -N(Et)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 teeth, -N(Et)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -C(O)-; L 3 is -CH2-;R 2and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 is -N(Et)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 This is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. Formulas (I)~(XVIII), (XXV)~(XXVII), In any particular embodiment of (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Et)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -N(Et)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any embodiment according to this paragraph, R1 R can be selected from H, Cl, F, Me, -CF3, -OMe, -CN, -C(O)NMe2, alkyl, propyl, isopropyl, and cyclopropyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), R 4 R is azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3R)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3S)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (S)-buta-4-yl-1,3-diol. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), and (XXXI), R 4 R is butane-1-ylone. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(cyanomethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), R 4 R is 1-(fluoromethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4R is 1-hydroxyl-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazole-5-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), R 4 R is (1-methyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-methoxycyclopropa-1-ylmethyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is methoxyethane-2-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), R 4 R is 1-(2-methoxyethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4This is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain embodiments, compounds of any of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 L is -NH-. In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 It is -N(Me)-.
[0173] In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2- and L 2 L is -C(O)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2- and L 2 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2- and L 2 In any particular embodiment of equations (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -NHCH2- and L 2 L is -SO2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2- and L 2 L is -NH-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2- and L 2 L is -N(Me)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -C(O)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -CH2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -C(H)= and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -SO2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 It is -NHCH2-; L 2 is -NH- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -N(Me)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -CH2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 -C(H)= and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -SO2-; L 3 is CH2- and R 2 and R 3Each of these is H. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), L 1 It is -NHCH2-; L 2 is -NH-;L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -N(Me)- and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 -C(H)= and L 3 is -CH2-;R2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -NHCH2- and L 2 is -C(O)-; L 3 is -CH2-;R2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1It is -NHCH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 This is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. Formulas (I)~(XVIII), (XXV In any particular embodiment of )~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -NHCH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -NHCH2-; L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any embodiment according to this paragraph, R1 R can be selected from H, Cl, F, Me, -CF3, -OMe, -CN, -C(O)NMe2, alkyl, propyl, isopropyl, and cyclopropyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), R 4 R is azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3R)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3S)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (S)-buta-4-yl-1,3-diol. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is butane-1-ylone. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(cyanomethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(fluoromethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4R is 1-hydroxyl-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazole-5-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (1-methyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-methoxycyclopropa-1-ylmethyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is methoxyethane-2-yl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(2-methoxyethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4This is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl. In any particular embodiment 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 embodiments, compounds of any of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 L is -NH-. In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 It is -N(Me)-.
[0174] In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2- and L 2 L is -C(O)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2- and L 2 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2- and L 2 In any particular embodiment of equations (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 is -N(Me)CH2- and L 2 L is -SO2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), and (XXXI), L 1 is -N(Me)CH2- and L 2 L is -NH-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -N(Me)CH2- and L 2 L is -N(Me)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -C(O)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -CH2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -C(H)= and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -SO2- and L 3is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -NH- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -N(Me)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 -C(H)= and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 It is -N(Me)CH2-; L 2 is -SO2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -NH-;L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -N(Me)- and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIII), L 1 It is -N(Me)CH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 It is (1-ethyl-1H-imidazole-5-yl)methyl. Formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII) In any particular embodiment, L 1 It is -N(Me)CH2-; L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -N(Me)- and L 3 is -CH2-;R2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1It is -N(Me)CH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1It is -N(Me)CH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -N(Me)CH2-; L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any embodiment according to this paragraph, R 1 R can be selected from H, Cl, F, Me, -CF3, -OMe, -CN, -C(O)NMe2, alkyl, propyl, isopropyl, and cyclopropyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), R 4 R is azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3R)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3S)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (S)-buta-4-yl-1,3-diol. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4R is butane-1-ylone. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(cyanomethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(fluoromethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-hydroxyl-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazole-5-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (1-methyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-methoxycyclopropa-1-ylmethyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is methoxyethane-2-yl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4R is 1-(2-methoxyethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain embodiments, compounds of any of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 L is -NH-. In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 It is -N(Me)-.
[0175] In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L1 is -OC(H,Me)- and L 2 L is -C(O)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 In any particular embodiment of equations (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 L is -SO2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 L is -NH-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 L is -N(Me)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -C(O)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2is -CH2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -C(H)= and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -SO2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -NH- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), and (XXXI), L 1 is -OC(H,Me)- and L 2 is -N(Me)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -C(O)-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -CH2-; L 3is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 -C(H)= and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -SO2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -NH-;L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -N(Me)- and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -C(O)-; L 3 is -CH2-;R2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 It is (1-ethyl-1H-imidazole-5-yl)methyl. Formulas (I) to (XVIII) In any particular embodiment of (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -NH-;L 3 is -CH2-;R 2and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -OC(H,Me)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -SO2-; L 3 is -CH2-; R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 is -OC(H,Me)- and L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any embodiment according to this paragraph, R 1 R can be selected from H, Cl, F, Me, -CF3, -OMe, -CN, -C(O)NMe2, alkyl, propyl, isopropyl, and cyclopropyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), R 4 R is azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4R is (3R)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is (3S)-azetidine-3-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is (S)-buta-4-yl-1,3-diol. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), and (XXXI), R 4 R is butane-1-ylone. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(cyanomethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(fluoromethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-hydroxyl-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 is isoxazole-5-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4R is (1-methyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-methoxycyclopropa-1-ylmethyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is methoxyethane-2-yl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is 1-(2-methoxyethyl)-cyclopropa-1-yl-methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 R is {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4 This is {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), R 4is 2-oxabicyclo[2.1.1]hexa-1-yl-methyl. In certain embodiments, compounds of any of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 L is -NH-. In certain embodiments, compounds of any of the formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), or their pharmaceutically active salts, tautomers, stereoisomers, and / or mixtures of stereoisomers are provided, where L 2 It is -N(Me)-.
[0176] In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH- and L 2 L is -C(O)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 , -SO2NH-; and L 2 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH- and L 2 In any particular embodiment of equations (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH- and L 2 L is -SO2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1is -SO2NH- and L 2 L is -NH-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 is -SO2NH- and L 2 L is -N(Me)-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -C(O)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -CH2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XVII), L 1 It is -SO2NH-;L 2 is -C(H)= and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -SO2- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -NH- and L 3is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -N(Me)- and L 3 is -CH2-. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -C(O)-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -CH2-; L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 -C(H)= and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -SO2-; L 3 is -CH2- and R 2 and R 3Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -NH-;L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -N(Me)- and L 3 is -CH2- and R 2 and R 3 Each of these is H. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XVII), L 1 It is -SO2NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 -C(H)= and L 3is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (2S)-oxetan-2-yl-methyl. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 Each of them is H; and R 4L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 is -N(Me)- and L 3 teeth,- CH2- and R 2 and R 3 Each of them is H; and R 4 L is (1-ethyl-1H-imidazole-5-yl)methyl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLIVII), L 1 It is -SO2NH-;L2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I)~(XVIII), (XXV)~(XXVII), (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is -COOH. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), and (XXXI), L 1 It is -SO2NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 is -SO2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 is -NH-;L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L2 is -N(Me)- and L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (2S)-oxetane-2-yl-methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 is -C(O)-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 is -CH2-; L 3 is -CH2-;R 2 and R 3 H is each; R 4 is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 L is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. In any particular embodiment of formulas (I) to (XVIII), (XXV) to (XXVII), (XXX), (XXXI), (XXXIX), and (XL to XLVII), L 1 It is -SO2NH-;L 2 -C(H)= and L 3 is -CH2-;R 2 and R 3 H is each; R 4is (1-ethyl-1H-imidazole-5-yl)methyl; and R 5 This is tetrazolyl, for example, 1H-1,2,3,4-tetrazole-5-yl. Formulas (I)~(XVIII), (XXV)~(XXVII), In any particular embodiment of (XXX), (XXXI), (XXXIX), and (XL-XLVII), L 1 It is -SO2NH-;L 2 is -SO2-; L 3...
Claims
1. A compound of formula I, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 1】 In the formula, A is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted cycloalkyl, or -NMe 2 , or -CF 3 And; Ring B is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, or a substituted or unsubstituted bicyclic ring; Ring C is a substituted or unsubstituted heterocycloalkyl, or a substituted or unsubstituted heterocycloalkenyl, as shown in the figure L 3 It includes at least one N bonded to it; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR 6 And; W is N or CR 14 , or C; when W is CR 14 , the adjacent dashed line represents a single bond; when W is C, the adjacent dashed line represents a double bond, or L 2 is -C(H)=; L 1 The bond is -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 Selected from the group consisting of NH-; L 2 The bond is -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -CF 2 -, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and 【Chemistry 2】 Selected from the group consisting of; L 3 is, -CH 2 - or -C(O)-; L 4 Either it does not exist, or L 4 is L 1 Furthermore, together with rings A and B, they form a condensed triring, and L 5 It does not exist; L 5 Either it does not exist, or L 5 is L 2 Furthermore, together with rings B and C, they form a condensed triring, L 4 It does not exist; R 4 is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylalkylene; R 5 は、-COOH、-COCF 3 、-C(OH)CF 3 、-CONHCN、-CONHOH、CONHOMe、-CONHSO 2 N (Me) 2 、-PO 3 H 2 、-PO(Me)(OH)、-SO 3 H、-SO 2 NH 2 、-SO 2 NHMe、-B(OH) 2 、 【Transformation 3】 Selected from the group consisting of and tetrazolyl; Each R 6 These are alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, and R. 11 R 12 NCO-, and R 11 R 12 Independently selected from a group consisting of N-; R 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; R 13 is hydrogen or alkyl; R 14 These are hydrogen, cyano, halo, hydroxyl, alkyl, haloalkyl, methyl, CH 2 F, or CH 2 It is OH; In the ceremony, L 1 ga-CH 2 It is O- and L 4 If it does not exist, and L 5 If it does not exist, L 2 is -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, or 【Chemistry 4】 is or L 3 The compound, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, is -C(O)- or both.
2. A compound of formula Ia, or a pharmaceutically acceptable salt or stereoisomer thereof: 【Transformation 5】 In the formula, A is a substituted or unsubstituted aryl, a substituted or unsubstituted heteroaryl, a substituted or unsubstituted cycloalkyl, or -NMe 2 , or -CF 3 And; Ring B is a substituted or unsubstituted aryl, or a substituted or unsubstituted heteroaryl; Ring C is either further unsubstituted, further substituted, and / or bridged; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR 6 And; W is N, CH, or C; if W is CH, adjacent dashed lines indicate single bonds; if W is C, adjacent dashed lines indicate double bonds or L 2 -C(H) =; L 1 is -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 Selected from the group consisting of NH-; L 2 The bond is -C(O)-, -CH 2 -, -C(H)=, -CF 2 -, -SO 2 -, -O-, -NH-, -N(Me)-, and 【Transformation 6】 Selected from the group consisting of; L 3 is, -CH 2 - or -C(O)-; L 4 Either it does not exist, or L 4 is L 1 Furthermore, together with rings A and B, they form a condensed triring, and L 5 It does not exist; L 5 is absent, or L 5 together with L 2 as well as rings B and C forms a fused tricyclic ring, and L 4 is absent; R 4 is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylalkylene; R 5 は、-COOH、-COCF 3 、-C(OH)CF 3 、-CONHCN、-CONHOH、CONHOMe、-CONHSO 2 N (Me) 2 、-PO 3 H 2 、-PO(Me)(OH)、-SO 3 H、-SO 2 NH 2 、-SO 2 NHMe、-B(OH) 2 、 【Transformation 7】 Selected from the group consisting of and tetrazolyl; Each R 6 These are alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, and R. 11 R 12 NCO-, and R 11 R 12 Independently selected from a group consisting of N-; R 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; R 13 is hydrogen or alkyl; In the formula, L 1 ga-CH 2 It is O- and L 4 If it does not exist, and L 5 If it does not exist, L 2 is -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, or 【Transformation 8】 is or L 3 The compound, or a pharmaceutically acceptable salt or stereoisomer thereof, is -C(O)- or both.
3. A compound according to claim 1 by formula IIa or IIb, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 9】 In the formula, A 1 A 2 A 3 A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR 1 And; B 1 , B 2 , B 3 , and B 4 Of these, 0, 1, or 2 are N, and the rest are CH or CR 2 And in equation IIb, B 4 It does not exist; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR 6 and; each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCOs; Each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCOs; Each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCOs; R 4 is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylalkylene; R 5 は、-COOH、-COCF 3 、-C(OH)CF 3 、-CONHCN、-CONHOH、CONHOMe、-CONHSO 2 N (Me) 2 、-PO 3 H 2 、-PO(Me)(OH)、-SO 3 H、-SO 2 NH 2 、-SO 2 NHMe、-B(OH) 2 、 【Chemistry 10】 Selected from the group consisting of and tetrazolyl; Each R 6 It 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, the compound, or a pharmaceutically acceptable salt thereof, or a stereoisomer.
4. A compound according to claim 1 by formula IIc, IId, IIg, or IIh, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 11】 In the formula, A 1 A 2 A 3 A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR 1 And; B 1 , B 2 , B 3 , and B 4 Of these, 0, 1, or 2 are N, and the rest are CH or CR 2 And in equation IIb, B 4 It does not exist; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR 6 And; Each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCOs; Each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCOs; Each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCOs; R 4 is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylalkylene; R 5 は、-COOH、-COCF 3 、-C(OH)CF 3 、-CONHCN、-CONHOH、CONHOMe、-CONHSO 2 N (Me) 2 、-PO 3 H 2 、-PO(Me)(OH)、-SO 3 H、-SO 2 NH 2 、-SO 2 NHMe、-B(OH) 2 、 【Chemistry 12】 Selected from the group consisting of and tetrazolyl; Each R 6 These are 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; R 14 These are hydrogen, cyano, halo, hydroxyl, methyl, CH 2 F, or CH 2 OH is; and o is 1, 2, 3, or 4, the compound, or a pharmaceutically acceptable salt thereof, or a stereoisomer.
5. A compound according to claim 1, represented by any of the following formulas, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 13-1】 【Chemistry 13-2】 【Chemistry 13-3】 [Chemistry 13-4] 【Chemistry 13-5】 【Chemistry 13-6】 In the formula, each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; Each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; Each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 is alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylalkylene; R 5 は、-COOH、-COCF 3 、-C(OH)CF 3 、-CONHCN、-CONHOH、CONHOMe、-CONHSO 2 N (Me) 2 、-PO 3 H 2 、-PO(Me)(OH)、-SO 3 H、-SO 2 NH 2 、-SO 2 NHMe、-B(OH) 2 、 【Chemistry 14】 Selected from the group consisting of 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 These are hydrogen, cyano, halo, hydroxyl, methyl, CH 2 F, or CH 2 OH, The compound, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein 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.
6. A compound of formula XXX, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 15】 In the formula, W is N, CH, or C; when W is CH, adjacent dashed lines indicate single bonds; when W is C, adjacent dashed lines indicate double bonds; A 1 A 2 A 3 A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR 1 And; B 1 , B 2 , B 3 , and B 4 Of these, 0, 1, or 2 are N, and the rest are CH or CR 2 And; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR 6 And; L 1 is -O-, -CH 2 -, -NH-, -N(Me)-, -N(Et)-, -OCH 2 -ien-CH 2 O-, -NHCH 2 -, -N(Me)CH 2 -, and -SO 2 Selected from the group consisting of NH-; L 2 The bond is -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -CF 2 -, -CHF-, -CH(OH)-, NH-, -N(Me)-, and 【Chemistry 16】 Selected from the group consisting of; L 3 is, -CH 2 - or -C(O)-; Each R 1 These are independently alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Selected from the group consisting of NCO-; Each R 2 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; Each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCOs; R 4 is an unsubstituted alkyl, substituted alkyl, unsubstituted heteroalkyl, substituted heteroalkyl, unsubstituted heterocycloalkylalkylalkylene, or substituted heterocycloalkylalkylalkylene; R 5 は、-COOH、-COCF 3 、-C(OH)CF 3 、-CONHCN、-CONHOH、CONHOMe、-CONHSO 2 N (Me) 2 、-PO 3 H 2 、-PO(Me)(OH)、-SO 3 H、-SO 2 NH 2 、-SO 2 NHMe、-B(OH) 2 、 【Chemistry 17】 Selected from the group consisting of and tetrazolyl; Each R 6 These are alkyl, substituted alkyl, halo, hydroxyl, alkoxyl, and R. 11 R 12 NCO-, and R 11 R 12 Independently selected from a group consisting of N-; R 11 is hydrogen or alkyl; R 12 is hydrogen or alkyl; R 13 is hydrogen or alkyl; and The compound, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof, wherein o is an integer from 0 to 4.
7. A compound of formula XXXI, or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof: 【Chemistry 18】 In the formula, W is N, CH, or C; if W is CH, adjacent dashed lines indicate a single element; A 1 A 2 A 3 A 4 , and A 5 Of these, 0, 1, or 2 are N, and the rest are CH or CR 1 And; D 1 , D 2 , and D 3 Of these, 0, 1, or 2 are N, and the rest are CH or CR 6 And; Each R 1 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; L 1 is -O-, -CH 2 -, -NH-, -N(Me)-, -N(Et)-, -OCH 2 -ien-CH 2 O-, -NHCH 2 -, -N(Me)CH 2 -, and -SO 2 Selected from the group consisting of NH-; L 2 The bond is -C(O)-, -CH 2 -, -C(H)=, -SO 2 -, -O-, -CF 2 -, -CHF-, -CH(OH)-, -NH-, -N(Me)-, and 【Chemistry 19】 Selected from the group consisting of; L 3 is, -C 2 - or -C(O)-; Each R 3 These include alkyl, substituted alkyl, halo, cyano, azide, alkoxy, haloalkoxy, and R 11 R 12 Independently selected from the group consisting of NCO-; R 4 is an unsubstituted alkyl, substituted alkyl, unsubstituted arylalkylene, substituted arylalkylene, heteroalkyl, substituted heteroalkyl, unsubstituted heteroarylalkylene, substituted heteroarylalkylene, unsubstituted heterocycloalkylalkylene, or substituted heterocycloalkylalkylalkylene; R 5 は、-COOH、-COCF 3 、-C(OH)CF 3 、-CONHCN、-CONHOH、CONHOMe、-CONHSO 2 N (Me) 2 、-PO 3 H 2 、-PO(Me)(OH)、-SO 3 H、-SO 2 NH 2 、-SO 2 NHMe、-B(OH) 2 、 【Chemistry 20】 Selected from the group consisting of and tetrazolyl; Each R 6 These are 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, the compound, or a pharmaceutically acceptable salt thereof, or a stereoisomer.
8. Each R 2 and R 3 A compound according to any one of the prior claims, wherein is H or F.
9. A compound according to any one of the prior claims, wherein m is 0 and o is 0.
10. A compound according to any one of the prior claims, wherein W is N or CH.
11. A compound according to any one of the prior claims, wherein W is C.
12. A compound according to any one of the prior claims, wherein W is CH.
13. A compound according to any one of the prior claims, wherein W is N.
14. R 4 However, azetidine-3-ylmethyl, (3R)-azetidine-3-ylmethyl, (3S)-azetidine-3-ylmethyl, (S)-buta-4-yl-1,3-diol, butan-1-ylone, 1-(cyanomethyl)-cyclopropa-1-ylmethyl, (1-ethyl-1H-imidazole-5-yl)-methyl, 1-(fluoromethyl)-cyclopropa-1-ylmethyl, 1-hydroxyl-cyclopropa-1-ylmethyl, isoxazole-5-ylmethyl, (1-methyl-1H-imidazole-5-yl)-methyl, 1-methoxy-cyclopropa-1-ylmethyl, methoxyethane-2-yl, 1-(2-methoxyethyl)-cyclo A compound according to any one of the prior claims, selected from the group consisting of propa-1-ylmethyl, {[1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}, {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}, {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}, oxetane-2-ylmethyl, (2S)-oxetane-2-ylmethyl, oxeran-3-ylmethyl, (3R)-oxeran-3-ylmethyl, 1,3-oxazole-2-ylmethyl, and 2-oxabicyclo[2.1.1]hexa-1-ylmethyl.
15. R 4 The compound described in any one of the prior claims, selected from the group consisting of (1-ethyl-1H-imidazole-5-yl)-methyl, oxetane-2-yl-methyl, (2S)-oxetane-2-yl-methyl, oxeran-3-yl-methyl, (3R)-oxeran-3-yl-methyl, and 1,3-oxazole-2-yl-methyl.
16. R 4 However, azetidine-3-ylmethyl, (3R)-azetidine-3-ylmethyl, (3S)-azetidine-3-ylmethyl, (S)-buta-4-yl-1,3-diol, butan-1-ylone, 1-(cyanomethyl)-cyclopropa-1-ylmethyl, 1-(fluoromethyl)-cyclopropa-1-ylmethyl, 1-hydroxyl-cyclopropa-1-ylmethyl, isoxazole-5-ylmethyl, (1-methyl-1H-imidazole-5-yl)-methyl, 1-methoxy-cyclopropa-1-ylmethyl A compound according to any one of the prior claims, selected from the group consisting of methoxyethane-2-yl, 1-(2-methoxyethyl)-cyclopropa-1-yl-methyl, {[1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}, {[(2R)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}, {[(2S)-1-(1,2-oxazole-3-carbonyl)azetidine-2-yl]methyl}, and 2-oxabicyclo[2.1.1]hexa-1-yl-methyl.
17. R 4 The compound according to any one of claims 1 to 15, selected from the group consisting of oxetane-2-ylmethyl and (1-ethyl-1H-imidazole-5-yl)methyl.
18. R 4 The compound according to any one of claims 1 to 15, wherein is oxetane-2-ylmethyl.
19. R 4 The compound according to any one of claims 1 to 15, wherein is (2S)-oxetane-2-ylmethyl.
20. R 4 The compound according to any one of claims 1 to 15, wherein is (1-ethyl-1H-imidazole-5-yl)methyl.
21. R 4 The compound according to any one of claims 1 to 15, selected from the group consisting of oxeran-3-ylmethyl and 1,3-oxazole-2-ylmethyl.
22. R 4 The compound according to any one of claims 1 to 15, wherein is (3R)-oxeran-3-yl-methyl.
23. R 4 The compound according to any one of claims 1 to 15, wherein is 1,3-oxazole-2-ylmethyl.
24. R 4 H is given by equation XXX The compound according to any one of the prior claims.
25. R 5 The compound according to any one of the prior claims, wherein the compound is -COOH or -COOMe.
26. R 5 The compound according to any one of the prior claims, wherein the compound is -COOH.
27. R 5 The compound according to any one of claims 1 to 24, wherein the compound is tetrazolyl.
28. R 5 The compound according to any one of claims 1 to 24, wherein the compound is 1H-1,2,3,4-tetrazole-5-yl.
29. L 2 However, -CH 2 -, -C(O)-, or -SO 2 - The compound according to any one of the prior claims.
30. L 2 The compound according to any one of claims 1 to 28, wherein is -CH= or -O-.
31. L 2 However, -CF 2 The compound according to any one of claims 1 to 28, wherein the compound is -, -CHF-, or -CHOH-.
32. L 2 ga-CH 2 - The compound according to any one of claims 1 to 29.
33. L 2 The compound according to any one of claims 1 to 28, wherein is -NH- or -N(Me)-.
34. L 2 The combination is by formula XXX. The compound according to any one of the prior claims.
35. L 3 ga-CH 2 - The compound according to any one of the prior claims.
36. L 3 The compound according to any one of claims 1 to 35, wherein is -C(O)-.
37. L 1 However, -CH 2 O-, or -OCH 2 - is the case according to equation XXX. A compound according to any of the prior claims.
38. L 1 ga-CH 2 It is O- and L 2 However, -CH 2 The compound according to any one of claims 1 to 29 and 37, wherein it is - or -CO-.
39. L 1 However, -CH 2 O- and L 3 The compound according to any one of claims 1 to 29 and 36 to 38, wherein is -C(O)-.
40. L 1 The compound according to any one of claims 1 to 36, wherein the compound is -O-.
41. L 1 ga-CH 2 The compound according to any one of claims 1 to 39, wherein it is O-.
42. L 1 The compound according to any one of claims 1 to 36, wherein the compound is -NH-.
43. L 1 The compound according to any one of claims 1 to 36, wherein the compound is -N(Me)-.
44. L 1 The compound according to any one of claims 1 to 36, wherein the compound is -N(Et)-.
45. L 1 However, -OCH 2 - The compound according to any one of claims 1 to 37.
46. L 1 The compound according to any one of claims 1 to 36, wherein the compound is -OC(H,Me)-.
47. L 1 ga-CH 2 A compound according to any one of claims 1 to 39 and 41, wherein the compound is O-.
48. L 1 However, - NHCH 2 - The compound according to any one of claims 1 to 36.
49. L 1 However, -N(Me)CH 2 - The compound according to any one of claims 1 to 36.
50. L 1 However, -SO 2 The compound according to any one of claims 1 to 36, wherein it is NH-.
51. A compound according to any one of the prior claims selected from the following, or a pharmaceutically acceptable salt or solvate thereof: Table 1-1 Table 1-2 Table 1-3 Table 1-4 Table 1-5 Table 1-6 Table 1-7 Table 1-8 Table 1-9 Table 1-10 Table 1-11 Table 1-12 Table 1-13 Table 1-14 Table 1-15 Table 1-16 Table 1-17 Table 1-18 Table 1-19 Table 1-20 Table 1-21 Table 1-22 Table 1-23 Table 1-24 Table 1-25 Table 1-26 Table 1-27 Table 1-28 Table 1-29 Table 1-30 Table 1-31 Table 1-32 Table 1-33 Table 1-34 Table 1-35 Table 1-36 Table 1-37 Table 1-38 Table 1-39 Table 1-40 Table 1-41 Table 1-42 Table 1-43 Table 1-44 Table 1-45 Table 1-46 Table 1-47 Table 1-48 Table 1-49 Table 1-50 Table 1-51 Table 1-52 Table 1-53 Table 1-54 Table 1-55 Table 1-56 Table 1-57 Table 1-58 Table 1-59 Table 1-60 Table 1-61 Table 1-62 Table 1-63 Table 1-64 Table 1-65 Table 1-66 Table 1-67 Table 1-68 Table 1-69 Table 1-70 Table 1-71 Table 1-72 Table 1-73 Table 1-74 Table 1-75 Table 1-76 Table 1-77 Table 1-78 Table 1-79 Table 1-80 Table 1-81 Table 1-82 Table 1-83 Table 1-84
52. A pharmaceutical composition comprising a compound according to any one of the prior claims, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, excipients, or diluents.
53. A method for treating a metabolic disease or disorder, comprising the step of administering to a patient in need a therapeutically effective amount of a compound according to any one of claims 1 to 51, or a pharmaceutically acceptable salt thereof, or a therapeutically effective amount of a pharmaceutical composition according to claim 52.
54. A compound according to any one of claims 1 to 51, or a pharmaceutical composition according to claim 52, for use in treatment.
55. A compound according to any one of claims 1 to 51, or a pharmaceutical composition according to claim 52, for use in the treatment of metabolic diseases or metabolic disorders.
56. Use of a compound according to any one of claims 1 to 51, or a pharmaceutical composition according to claim 52, in the manufacture of a pharmaceutical for the treatment of metabolic diseases or metabolic disorders.