Heteroaryl compounds and their use in the treatment of medical conditions

Abstract

This invention provides heteroaryl compounds, pharmaceutical compositions, and their use in treating diseases or conditions such as proliferative disorders, inflammatory disorders, autoimmune disorders, or metabolic disorders.

Description

Cross-reference to related applications

[0001] This application claims the benefit and priority of U.S. Provisional Patent Application No. 63 / 585,430, filed on September 26, 2023, the contents of which are hereby incorporated by reference in their entirety. Technical Field

[0002] This invention provides heteroaryl compounds, pharmaceutical compositions, and their use in treating diseases or conditions such as proliferative disorders, inflammatory disorders, autoimmune disorders, or metabolic disorders. Background Technology

[0003] Despite the extensive research efforts and scientific advancements reported in the literature regarding cancer treatment, the disease remains a significant health concern. Solid tumors, including prostate, breast, and lung cancer, remain very prevalent in the world's population. Current treatment options for these cancers are not effective for all patients and / or may have serious adverse side effects. Furthermore, novel therapies that achieve anti-cancer effects through different mechanisms offer opportunities for more effective treatment of cancer and / or for treating cancers that have developed resistance to existing drugs.

[0004] Inflammatory conditions affect a significant number of patients and often involve a biological response to a stimulus that causes the immune system to attack the body's own cells or tissues. This can lead to abnormal inflammation and result in chronic pain, redness, swelling, stiffness, and / or damage to normal tissues. Current treatment options for these inflammatory conditions are not effective for all patients and / or may have serious adverse side effects.

[0005] Nicotinamide adenine dinucleotide (NAD+) is a cofactor that plays an important role in many essential physiological processes such as metabolism, energy production, DNA repair, and signal transduction. Nicotinamide phosphoribosyltransferase (NAmPRTase or NAMPT) is essential for the biosynthesis of NAD+. In mammals, the rate-limiting step in NAD+ biosynthesis is the rescue of NAM and its conversion to nicotinamide mononucleotide (NMN) catalyzed by NAMPT. Therefore, inhibition of NAMPT leads to NAD+ depletion and reduced proliferation and even death of diseased cells. Consequently, NAMPT inhibitors can be used to treat various cancers, metabolic disorders, and inflammatory conditions.

[0006] There is a need to develop new treatments and compounds to treat diseases or symptoms associated with NAMPT activity. This invention addresses these needs and provides other related advantages. Summary of the Invention

[0007] This invention provides heteroaryl compounds, pharmaceutical compositions, and their uses in treating diseases or conditions such as proliferative disorders, inflammatory disorders, autoimmune disorders, or metabolic disorders. In particular, one aspect of the invention provides a series of heteroaryl compounds, such as those represented by Formula I: (I) Or a pharmaceutically acceptable salt thereof, wherein the variables are as defined in the specific embodiments. Further descriptions in the specific embodiments include additional series of heteroaryl compounds. These compounds may be part of a pharmaceutical composition comprising a pharmaceutically acceptable carrier.

[0008] Another aspect of the present invention provides a series of heteroaryl compounds, such as those represented by formula I-1: (I-1) Or a pharmaceutically acceptable salt thereof, wherein the variables are as defined in the specific embodiments. Further descriptions in the specific embodiments include additional series of heteroaryl compounds. These compounds may be part of a pharmaceutical composition comprising a pharmaceutically acceptable carrier.

[0009] Another aspect of the invention provides a method for treating a disease or condition mediated by NAMPT. The method comprises administering a therapeutically effective amount of a compound described herein, such as a compound of formula I, I-1, IA, IB, IC, or ID, to a subject in need to treat the disease or condition, as further described in the specific embodiments.

[0010] Another aspect of the present invention provides a method for inhibiting the activity of NAMPT. The method comprises contacting NAMPT with an effective amount of a compound described herein (such as a compound of formula I, I-1, IA, IB, IC, or ID) to inhibit the activity of the NAMPT, as further described in the specific embodiments. Detailed Implementation

[0011] This invention provides heteroaryl compounds, pharmaceutical compositions, and their uses in the treatment of diseases or conditions such as proliferative disorders, inflammatory disorders, autoimmune disorders, or metabolic disorders. Unless otherwise noted, the invention is practiced using conventional techniques of organic chemistry, pharmacology, molecular biology (including recombinant techniques), cell biology, biochemistry, and immunology. Such techniques are described in references such as “Comprehensive Organic Synthesis” (edited by BM Trost and I. Fleming, 1991–1992); “Handbook of Experimental Immunology” (edited by DM Weir and CC Blackwell); “Current Protocols in Molecular Biology” (edited by FM Ausubel et al., 1987 and regularly updated); and “Current Protocols in Immunology” (edited by JE Coligan et al., 1991), each of which is incorporated herein by reference in its entirety.

[0012] The various aspects of the invention are described in sections below; however, the aspects of the invention described in a particular section are not limited to any particular section. Furthermore, when a variable is not subsequently defined, its prior definition shall prevail.

[0013] definition The compounds of this invention include those generally described herein, and are further illustrated by way of example the classes, subclasses and species disclosed herein. As used herein, unless otherwise indicated, the following definitions will apply. Unless otherwise indicated, these definitions apply whether the terms are used alone or in combination with other terms. Thus, the definition of “alkyl” applies to “alkyl” as well as the “alkyl” part of “-O-alkyl”, etc. For the purposes of this invention, chemical elements were identified according to the periodic table (CAS version), 75th edition, Handbook of Chemistry and Physics. Furthermore, the general principles of organic chemistry are described in “Organic Chemistry,” Thomas Sorrell, University Science Books, Sausalito: 1999, and “March's Advanced Organic Chemistry,” 5th edition, eds., Smith, MB and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference.

[0014] As used herein, the term "aliphatic" or "aliphatic group" means a straight-chain (i.e., unbranched) or branched substituted or unsubstituted hydrocarbon chain that is fully saturated or contains one or more unsaturated units, or a monocyclic or bicyclic hydrocarbon (also referred to herein as "alicyclic") that is fully saturated or contains one or more unsaturated units but is not aromatic, having a single connection point to the rest of the molecule. Unless otherwise stated, an aliphatic group contains 1-6 aliphatic carbon atoms. In some embodiments, the aliphatic group contains 1-5 aliphatic carbon atoms. In other embodiments, the aliphatic group contains 1-4 aliphatic carbon atoms. In still other embodiments, the aliphatic group contains 1-3 aliphatic carbon atoms, and in yet another embodiment, the aliphatic group contains 1-2 aliphatic carbon atoms. In some embodiments, "alicyclic" refers to a monocyclic C3-C6 hydrocarbon that is fully saturated or contains one or more unsaturated units but is not aromatic, having a single connection point to the rest of the molecule. Suitable aliphatic groups include, but are not limited to, straight-chain or branched substituted or unsubstituted alkyl, alkenyl, alkynyl and their hybrid groups, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

[0015] As used herein, the term "bicyclic ring" or "bicyclic ring system" refers to any bicyclic ring system, i.e., a carbocyclic or heterocyclic ring system, saturated or having one or more unsaturated units, having one or more common atoms between the two rings of the ring system. Therefore, the term includes any permissible ring fusion, such as ortho-fusion or spirocyclic. As used herein, the term "heterobicyclic" is a subset of "bicyclic," requiring the presence of one or more heteroatoms in one or both rings of the bicyclic ring. Such heteroatoms may be present at ring junctions and are optionally substituted, and may be selected from nitrogen (including N-oxides), oxygen, sulfur (including oxidized forms such as sulfones and sulfonates), phosphorus (including oxidized forms such as phosphates), boron, etc. In some embodiments, the bicyclic group has 7-12 ring members and 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. As used herein, the term "bridged bicyclic" refers to any bicyclic ring system, i.e., a carbocyclic or heterocyclic ring system, saturated or partially unsaturated, having at least one bridge. As defined by IUPAC, a “bridge” is an unbranched chain or atom or valence bond connecting two bridgeheads, wherein a “bridgehead” is any skeletal atom of the ring system bonded to three or more skeletal atoms (excluding hydrogen). In some embodiments, the bridged bicyclic group has 7-12 ring members and 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Such bridged bicyclic groups are well known in the art and include those groups listed below, wherein each group is connected to the remainder of the molecule at any substituted carbon or nitrogen atom. Unless otherwise stated, the bridged bicyclic group may optionally be substituted with one or more substituents as listed for aliphatic groups. Alternatively or additionally, any substituted nitrogen atom in the bridged bicyclic group may optionally be substituted. Exemplary bicyclic rings include: An exemplary bridged double ring includes: .

[0016] The term "lower alkyl" refers to C 1-4 Straight-chain or branched alkyl groups. Exemplary lower alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0017] The term "lower haloalkyl" refers to a C-aryl group that has been substituted with one or more halogen atoms. 1-4 Straight-chain or branched alkyl groups.

[0018] The term "heteroatom" refers to one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (including any oxidized form of nitrogen, sulfur, phosphorus, or silicon; any quaternized form of basic nitrogen; or a substituted nitrogen in a heterocyclic ring, such as N (e.g., in 3,4-dihydro-2-) H -pyrrole group), NH (as in pyrroleyl group) or NR + (e.g., in N-substituted pyrroleyl groups).

[0019] As used in this article, the term "unsaturated" means that a part has one or more unsaturated units.

[0020] As used in this article, the term "divalent C" 1-8 (or C) 1-6 "Saturated or unsaturated straight or branched hydrocarbon chains" refers to straight or branched divalent alkylene, alkenylene, and ynylene chains as defined herein.

[0021] The term "alkylene" refers to a divalent alkyl group. An "alkylene chain" is a polymethylene group, i.e., –(CH2). n – where n is a positive integer, preferably 1 to 6, 1 to 4, 1 to 3, 1 to 2, or 2 to 3. The substituted alkylene chain is a polymethylene group in which one or more methylene hydrogen atoms are replaced by a substituent. Suitable substituents include those described below for substituted aliphatic groups.

[0022] The term "-(C0 alkylene)-" refers to a bond. Therefore, the term "-(C0 alkylene)-" refers to a bond. 0-3 alkylene)-” encompasses both the bond (i.e., C0) and the bond (-(C) 1-3 (alkylene) group.

[0023] The term "alkenyl" refers to a divalent alkenyl group. A substituted alkenyl chain is a polymethylene group containing at least one double bond, wherein one or more hydrogen atoms are replaced by substituents. Suitable substituents include those described below for substituted aliphatic groups.

[0024] The term "halogen" refers to F, Cl, Br, or I.

[0025] The term "aryl" when used alone or as part of a larger portion of "aranyl," "aranalkoxy," or "aranoxyalkyl" refers to a monocyclic or bicyclic ring system having a total of five to fourteen ring members, wherein at least one ring in the system is aromatic, and wherein each ring in the system contains 3 to 7 ring members. The term "aryl" may be used interchangeably with the term "aryl ring." In some embodiments of the invention, "aryl" refers to an aromatic ring system, including but not limited to phenyl, biphenyl, naphthyl, anthracene, etc., which may have one or more substituents. The scope of the term "aryl" as used herein also includes groups in which an aromatic ring is fused with one or more non-aromatic rings, such as indanyl, phthalimide, naphthalimide, phenanthridine, or tetrahydronaphthyl, etc. The term "phenylene" refers to a polyvalent phenyl having an appropriate number of open valence states to satisfy the bonding requirements of the groups to which it is attached. For example, when "phenylene" has two groups attached to it (e.g., ), which is a divalent phenyl; when "phenylene" has three groups attached to it (e.g., It is a trivalent phenyl group. The term "aryl" refers to a divalent aryl group.

[0026] The terms "heteroaryl" and "heteroary-" used alone or as part of a larger portion (e.g., "heteroarylalkyl" or "heteroarylalkoxy") refer to a group having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; enjoying 6, 10, or 14 π electrons in the cyclic array; and having one to five heteroatoms in addition to carbon atoms. The term "heteroatom" refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur and any quaternized form of basic nitrogen. Heteroaryl groups include, but are not limited to, thienyl, furanyl, pyrroleyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiazolyl, pyridinyl, pyrazinyl, indoleazinyl, purine, naphthidyl, and pteridinyl. As used herein, the terms "heteroaryl" and "heteroary-" also include groups in which a heteroaryl ring is fused with one or more aryl, alicyclic, or heterocyclic rings, wherein, unless otherwise stated, the linking group or linking point is on the heteroaryl ring or on one of the rings fused with the heteroaryl ring. Non-limiting examples include indolyl, isoindolyl, benzothiophenyl, benzofuranyl, dibenzofuranyl, indazoleyl, benzimidazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, terolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4- H–Quinazinyl, carbazolyl, acridinel, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, and tetrahydroisoquinolinyl. Heteroaryl groups can be monocyclic or bicyclic. The term "heteroaryl" is used interchangeably with the terms "heteroaryl ring," "heteroaryl group," or "heteroarylene," any of which includes the optionally substituted ring. The term "heteroarylalkyl" refers to an alkyl group substituted with a heteroaryl group, wherein both the alkyl and heteroaryl portions are independently optionally substituted.

[0027] The term "hybrid aryl" refers to a polyvalent heteroaryl group that has an appropriate number of open valence states to satisfy the bonding requirements of the groups to which it is attached. For example, when a "hybrid aryl" has two groups attached to it, it is a divalent heteroaryl; when a "hybrid aryl" has three groups attached to it, it is a trivalent heteroaryl.

[0028] As used herein, the terms “heterocyclic,” “heterocyclic group,” “heterocyclic radical,” and “heterocyclic ring” are used interchangeably and refer to a stable 5- to 7-membered monocyclic or 7- to 10-membered bicyclic heterocyclic moiety that is saturated or partially unsaturated and has one or more, preferably one to four, heteroatoms as defined above, in addition to a carbon atom. When the term “nitrogen” is used to refer to the ring atom of a heterocycle, it includes substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0–3 heteroatoms selected from oxygen, sulfur, or nitrogen, nitrogen can be N (e.g., in 3,4-dihydro-2-dihydrogen ... H– In pyrroleyl), NH (as in pyrrolealkyl) or + NR (as in) N– (In substituted pyrrolidinyl groups).

[0029] Heterocyclic rings can be attached to their side groups at any heteroatom or carbon atom that results in a stable structure, and any ring atom can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic groups include, but are not limited to, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazine, dioxane, dioxopentyl, diazaheptanyl, oxazaheptanyl, thiazoheptanyl, morpholinyl, 2-oxa-6-azaspiro[3.3]heptane, and quininecycloyl. The terms “heterocyclic,” “heterocyclic group,” “heterocyclic ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical” are used interchangeably herein and also include groups in which the heterocyclic ring is fused with one or more aryl, heteroaryl, or alicyclic rings, such as indolinel, 3 H–Indolyl, chromyl, phenanthridine, or tetrahydroquinolinyl. The heterocyclic group can be monocyclic or bicyclic. The term "heterocyclic alkyl" refers to an alkyl group substituted with a heterocyclic group, wherein the alkyl and heterocyclic portions are independently optional substitutions. The term "oxo-heterocyclic" refers to a heterocyclic group substituted with one or more oxo groups. The term "hypo-heterocyclic" refers to a polyvalent heterocyclic group having an appropriate number of open valence states to satisfy the bonding requirements of the groups to which it is attached. For example, when a "hypo-heterocyclic" group has two groups attached to it, it is a divalent heterocyclic group; when a "hypo-heterocyclic" group has three groups attached to it, it is a trivalent heterocyclic group. The term "oxo-hypo-heterocyclic" refers to a polyvalent oxo-heterocyclic group having an appropriate number of open valence states to satisfy the bonding requirements of the groups to which it is attached.

[0030] As used herein, the term "partially unsaturated" refers to a ring moiety comprising at least one double or triple bond. The term "partially unsaturated" is intended to cover rings having multiple unsaturated sites, but is not intended to include aryl or heteroaryl moiety as defined herein.

[0031] As described herein, the compounds of the present invention may contain an "optionally substituted" portion. Generally, the term "substituted," whether or not preceded by the term "optionally," means that one or more hydrogens of the specified portion are replaced by suitable substituents. Unless otherwise noted, the "optionally substituted" group may have suitable substituents at each substituted position of the group, and the substituents at each position may be the same or different when more than one position in any given structure can be substituted by more than one substituent selected from the specified group. The combinations of substituents contemplated in this invention are preferably those that result in the formation of stable or chemically viable compounds. The term "stable," as used herein, means a compound that remains substantially unchanged when subjected to conditions permissible for its preparation, testing, and, in some embodiments, for its recovery and for use in one or more of the purposes disclosed herein.

[0032] Each optional substituent on the substituted carbon is independently selected from the following monovalent substituents: halogen; –(CH2). 0– 4R°;–(CH2) 0–4 OR°;-O(CH2) 0-4 R°、–O–(CH2) 0–4 C(O)OR°;–(CH2) 0–4 CH(OR°)2;–(CH2) 0–4 SR°; –(CH2) that can be replaced by R° 0–4 Ph; can be replaced by R° –(CH2) 0–4 O(CH2) 0–1 Ph; –CH=CH can be substituted by R°; –(CH2) can be substituted by R°. 0–4 O(CH2)0–1 -pyridyl; –NO2; –CN; –N3; -(CH2) 0–4 N(R°)2;–(CH2) 0–4 N(R°)C(O)R°; –N(R°)C(S)R°; –(CH2) 0–4 N(R°)C(O)NR°2; -N(R°)C(S)NR°2; –(CH2) 0–4 N(R°)C(O)OR°; –N(R°)N(R°)C(O)R°; –N(R°)N(R°)C(O)NR°2; –N(R°)N(R°)C(O)OR°; –(CH2) 0–4 C(O)R°; –C(S)R°; –(CH2) 0–4 C(O)OR°;–(CH2) 0–4 C(O)SR°;-(CH2) 0–4 C(O)OSiR°3;–(CH2) 0–4 OC(O)R°;–OC(O)(CH2) 0–4 SR–, SC(S)SR°; –(CH2) 0–4 SC(O)R°;–(CH2) 0–4 C(O)NR°2; –C(S)NR°2; –C(S)SR°; –SC(S)SR°, -(CH2) 0–4 OC(O)NR°2; -C(O)N(OR°)R°; –C(O)C(O)R°; –C(O)CH2C(O)R°; –C(NOR°)R°; –(CH2) 0–4 SSR°;–(CH2) 0–4 S(O)2R°;–(CH2) 0–4 S(O)₂OR°;–(CH₂) 0–4 OS(O)2R°; –S(O)2NR°2; –S(O)(NR°)R°; –S(O)2N=C(NR°2)2; –(CH2) 0–4 S(O)R°; -N(R°)S(O)2NR°2; –N(R°)S(O)2R°; –N(OR°)R°; –C(NH)NR°2; –P(O)2R°; –P(O)R°2; –OP(O)R°2; –OP(O)(OR°)2; SiR°3; –(C 1–4 (linear or branched alkylene)O–N(R°)2; or –(C 1–4 (Straight-chain or branched alkylene)C(O)O–N(R°)2.

[0033] Each R° is independently for hydrogen, C 1–6 Aliphatic groups, –CH2Ph, –O(CH2)0–1 Ph, -CH2-(5-6 membered heteroaryl ring), or a 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or, notwithstanding the foregoing definition, two independently occurring R° together with their intervening atoms form a 3-12 membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted by divalent substituents selected from =O and =S on the saturated carbon atom of R°; or each R° may optionally be substituted by a monovalent substituent independently selected from: halogens, -(CH2). 0–2 R ● 、–(halogenated) ● ), –(CH2) 0–2 OH, –(CH2) 0–2 OR ● –(CH2) 0–2 CH(OR ● )2;-O(halogenated R ● –CN, –N3, –(CH2) 0–2 C(O)R ● –(CH2) 0–2 C(O)OH, –(CH2) 0–2 C(O)OR ● –(CH2) 0–2 SR ● –(CH2) 0– 2SH、–(CH2) 0–2 NH2、–(CH2) 0–2 NHR ● –(CH2) 0–2 NR ● 2, –NO2, –SiR ● 3. –OSiR ● 3. -C(O)SR ● 、–(C 1–4 (straight-chain or branched alkylene)C(O)OR ● Or –SSR ● .

[0034] Each R ● Selected independently from C 1–4 Aliphatic group, –CH2Ph, –O(CH2) 0–1 Ph or a 5–6 member saturated, partially unsaturated, or aryl ring having 0–4 independent heteroatoms selected from nitrogen, oxygen, or sulfur, wherein each R ● It is unsubstituted, or substituted with one or more halogens if there is a preceding halogenation; or the optional substituent on the saturated carbon is independently selected from the following divalent substituents: =O, =S, =NNR. *2、=NNHC(O)R * =NNHC(O)OR * =NNHS(O)2R * =NR * =NOR * 、 –O(C(R) * 2)) 2–3 O – or –S(C(R) * 2)) 2–3 S–, or a divalent substituent bonded to an ortho-substituted carbon atom of an "optionally substituted" group, is –O(CR). * 2) 2–3 O–, where each independently occurring R * Selected from hydrogen, C 1–6 It is an aliphatic group or an unsubstituted 5–6 saturated, partially unsaturated or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0035] When R * It is C 1–6 When aliphatic groups are present, R * Optional halogenated, –R ● 、-(halogenated) ● -OH, -OR ● –O (halogenated R) ● ), –CN, –C(O)OH, –C(O)OR ● –NH2, –NHR ● –NR ● 2 or –NO2 substitution, where each R ● Selected independently from C 1–4 Aliphatic group, –CH2Ph, –O(CH2) 0–1 Ph or a 5–6 member saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein each R ● It is either unsubstituted or, in the case of prior halogenation, substituted by one or more halogens.

[0036] The optional substituents on the substituted nitrogen are independently –R † –NR † 2. –C(O)R † –C(O)OR † –C(O)C(O)R † –C(O)CH2C(O)R † -S(O)2R † -S(O)2NR † 2. –C(S)NR † 2. –C(NH)NR † 2 or –N(R)† )S(O)2R † ; where each R † Independently hydrogen, C 1–6 Aliphatic group, unsubstituted –OPh, or unsubstituted 5–6-membered saturated, partially unsaturated, or aryl ring having 0–4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur, or two independently occurring R groups. † Together with their intervening atoms, they form unsubstituted 3–12-membered saturated, partially unsaturated, or aryl monocyclic or bicyclic rings with 0–4 independently selected heteroatoms chosen from nitrogen, oxygen, or sulfur; wherein R † It is C 1–6 When aliphatic groups are present, R † Optional halogenated, –R ● -(halogenated R) ● -OH, -OR ● –O (halogenated R) ● ), –CN, –C(O)OH, –C(O)OR ● –NH2, –NHR ● –NR ● 2 or –NO2 substitution, where each R ● Selected independently from C 1–4 Aliphatic group, –CH2Ph, –O(CH2) 0–1 Ph or a 5–6 member saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, wherein each R ● It is either unsubstituted or, in the case of prior halogenation, substituted by one or more halogens.

[0037] As used herein, the term "pharmaceutically acceptable salt" means that salts suitable for use in contact with the tissues of humans and lower animals within the limits of reasonable medical judgment without excessive toxicity, irritation, allergic reactions, etc., and in proportion to a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, SM Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1–19, which is incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of the present invention include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts include salts formed by amino groups with inorganic acids (such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid) or with organic acids (such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid) or by other methods used in the art (such as ion exchange). Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, hydrogen sulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentanepropionate, disaccharide, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucono-heptahydrate, glyceryl phosphate, gluconate, hemisulfate, heptahydrate, hexanoate, hydroiodate, 2-hydroxy-ethanesulfonate, lacturonate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, dihydroxynaphthalate, pectate, persulfate, 3-phenylpropionate, phosphate, neopentanoate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc.

[0038] Furthermore, acids generally considered suitable for forming pharmaceutically useful salts from basic medicinal compounds are discussed, for example, in the following literature: P. Stahl et al., Camille G. (edited) Handbook of Pharmaceutical Salts. Properties, Selection and Use. (2002) Zurich: Wiley-VCH; S. Berge et al. Journal of Pharmaceutical Sciences (1977) 66(1) 1-19; P. Gould, International J. of Pharmaceutics (1986) 33 201-217; Anderson et al., The Practice of Medicinal Chemistry (1996), Academic Press, New York; and The Orange Book(Food & Drug Administration, Washington, DC, see its website). This publicly available information is incorporated herein by reference.

[0039] Salts derived from suitable bases include alkali metals, alkaline earth metals, ammonium, and nitrogen. + (C 1–4 Alkyl)4 salts. Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, etc. Where appropriate, further pharmaceutically acceptable salts include non-toxic ammonium, quaternary ammonium, and amine cations formed using counterions (such as halide, hydroxide, carboxyl, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate).

[0040] Unless otherwise stated, the structures described herein are intended to include all isomers (e.g., enantiomers, diastereomers, and geometric (or conformations)) of the structures; for example, R and S configurations, Z and E double bond isomers, and Z and E conformational isomers for each asymmetry center. Therefore, single stereochemical isomers of the compounds of the present invention, as well as mixtures of enantiomers, diastereomers, and geometric (or conformations), are all within the scope of the present invention. Unless otherwise stated, all tautomers of the compounds of the present invention are within the scope of the present invention. The present invention includes compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the structure of the present invention but including those with hydrogen replaced by deuterium or tritium, or those with... 13 C or 14 Compounds that enrich carbon to replace carbon are within the scope of this invention. Such compounds can be used, for example, as analytical tools, as probes in bioassays, or as therapeutic agents according to this invention.

[0041] A mixture of diastereomers can be separated into their individual diastereomers based on their physicochemical differences using methods known to those skilled in the art (e.g., by chromatography and / or fractional crystallization). Enantiomers can be separated by reacting the enantiomer mixture with a suitable optically active compound (e.g., a chiral auxiliary agent, such as a chiral alcohol or moselyl chloride) to convert the enantiomer mixture into a mixture of diastereomers, separating the diastereomers, and converting (e.g., hydrolyzing) the individual diastereomers into their respective pure enantiomers. Alternatively, specific enantiomers of the compounds of the present invention can be prepared by asymmetric synthesis. Furthermore, in the case where the molecule contains a basic functional group (e.g., amino) or an acidic functional group (e.g., carboxylic acid), a diastereomer salt is formed with a suitable optically active acid or base, followed by resolution of the thus formed diastereomer by fractional crystallization or chromatographic methods known in the art, and subsequently recovery of the pure enantiomer.

[0042] Individual stereoisomers of the compounds of the present invention may, for example, be substantially free of other isomers, or may exist, for example, in racemic form or mixed with all other or other selected stereoisomers. The chiral center in the compounds of the present invention may have a [characteristic / structure]. IUPAC The definition of the 1974 recommendation S or R Configuration. Furthermore, if the compounds described herein exist in a transisomer form (e.g., a substituted biaryl group), all such transisomer forms are considered part of this invention.

[0043] Chemical names, common names, and chemical structures can be used interchangeably to describe the same structure. If both chemical structures and chemical names are used to describe a chemical compound, and there is ambiguity between the structure and the name, the structure shall prevail. It should also be noted that any unsaturated carbon atoms and heteroatoms in the text, schemes, examples, and tables are considered to have a sufficient number of hydrogen atoms to satisfy valence bonds.

[0044] As used herein, the term “a (species)” means “one (species) or more (species)” and includes the plural form unless the context otherwise requires.

[0045] The term "alkyl" refers to a saturated straight-chain or branched hydrocarbon, such as a straight-chain or branched group with 1-12, 1-10, or 1-6 carbon atoms, referred to herein as C1-C1, respectively. 12 Alkyl, C1-C 10 Alkyl and C1-C6 alkyl. Exemplary alkyl groups include, but are not limited to, methyl, ethyl, propyl, isopropyl, 2-methyl-1-propyl, 2-methyl-2-propyl, 2-methyl-1-butyl, 3-methyl-1-butyl, 2-methyl-3-butyl, 2,2-dimethyl-1-propyl, 2-methyl-1-pentyl, 3-methyl-1-pentyl, 4-methyl-1-pentyl, 2-methyl-2-pentyl, 3-methyl-2-pentyl, 4-methyl-2-pentyl, 2,2-dimethyl-1-butyl, 3,3-dimethyl-1-butyl, 2-ethyl-1-butyl, butyl, isobutyl, tert-butyl, pentyl, isopentyl, neopentyl, hexyl, heptyl, octyl, etc.

[0046] The term "cycloalkyl" refers to a monovalent saturated cyclic, bicyclic, or bridged cyclic (e.g., adamantyl) hydrocarbon group derived from cycloalkanes with 3-12, 3-8, 4-8, or 4-6 carbons, and is referred to herein, for example, as "C3-C6 cycloalkyl". Exemplary cycloalkyl groups include cyclohexyl, cyclopentyl, cyclobutyl, and cyclopropyl. The term "cycloalkylene" refers to a divalent cycloalkyl group.

[0047] The term "haloalkyl" refers to an alkyl group substituted with at least one halogen. Exemplary haloalkyl groups include -CH2F, -CHF2, -CF3, -CH2CF3, -CF2CF3, etc. The term "haloalkylene" refers to a divalent haloalkyl group.

[0048] The term "hydroxyalkyl" refers to an alkyl group that is substituted with at least one hydroxyl group. Exemplary hydroxyalkyl groups include -CH2CH2OH, -C(H)(OH)CH3, -CH2C(H)(OH)CH2CH2OH, etc.

[0049] The generally accepted terms “alkenyl” and “alkynyl” in this field refer to unsaturated aliphatic groups that are similar in length and possible substitution to the alkyl groups described above, but each contains at least one double or triple bond.

[0050] The term "alkoxy" as generally accepted in this art refers to an alkyl group as defined above and having an oxygen group attached thereto. Representative alkoxy groups include methoxy, ethoxy, propoxy, tert-butoxy, etc. The term "haloalkoxy" refers to an alkoxy group substituted with at least one halogen. Exemplary haloalkoxy groups include -OCH2F, -OCHF2, -OCF3, -OCH2CF3, -OCF2CF3, etc.

[0051] The term "oxo" is generally accepted in this field to refer to an "=O" substituent. For example, cyclopentane substituted with an oxo group is cyclopentanone.

[0052] symbol" " " indicates a connection point.

[0053] When any substituent or variable appears more than once in any composition or compound of the present invention, unless otherwise indicated, its definition at each occurrence is independent of its definition at each other occurrence.

[0054] One or more compounds of the present invention can exist in an unsolvated form and in a solvated form with pharmaceutically acceptable solvents (such as water, ethanol, etc.), and the present invention is intended to cover both solvated and unsolvated forms. "Solvate" means the physical association of a compound of the present invention with one or more solvent molecules. This physical association involves varying degrees of ionic and covalent bonding, including hydrogen bonding. In some cases, solvates will be separable, for example when one or more solvent molecules are bound in the lattice of a crystalline solid. "Solvate" encompasses both solution phases and separable solvates. Non-limiting examples of suitable solvates include ethanolates, methanolates, etc. "Hydrate" is a solvate in which the solvent molecule is H₂O.

[0055] As used herein, the terms "subject" and "patient" are used interchangeably and refer to an organism to be treated by the methods of the present invention. Such organisms preferably include, but are not limited to, mammals (e.g., rodents, apes, horses, cattle, pigs, dogs, cats, etc.), and most preferably include humans.

[0056] The term "IC" is generally accepted in this field. 50 "This refers to the concentration of the compound required to achieve 50% inhibition of the target."

[0057] As used herein, the term "effective amount" means an amount of compound sufficient to achieve a beneficial or desired outcome (e.g., therapeutic, ameliorative, inhibitory, or preventative outcome). An effective amount may be administered by single or multiple applications, application, or dosing, and is not intended to be limited to a particular formulation or route of administration. As used herein, the term "treatment" includes any effect that results in improvement of symptoms, disease, condition, etc., or an amelioration of their symptoms, such as reduction, decrease, modulation, improvement, or elimination.

[0058] As used herein, the term "pharmaceutical composition" refers to a combination of an active agent and a carrier (inert or active) such that the composition is particularly suitable for diagnostic or therapeutic use in vivo or in vitro.

[0059] As used herein, the term “pharmaceuticalally acceptable carrier” means any standard pharmaceutical carrier, such as phosphate-buffered saline solutions, water, emulsions (e.g., oil / water or water / oil emulsions), and various types of wetting agents. Compositions may also include stabilizers and preservatives. For examples of carriers, stabilizers, and adjuvants, see, for example, Martin, Remington's Pharmaceutical Sciences, 15th edition, Mack Publ. Co., Easton, PA

[1975] .

[0060] For therapeutic purposes, salts of the compounds of the present invention are considered pharmaceutically acceptable. However, salts of non-pharmaceutically acceptable acids and bases may also be used, for example, to prepare or purify pharmaceutically acceptable compounds.

[0061] Furthermore, when the compounds of the present invention contain both a basic moiety (such as, but not limited to, pyridine or imidazole) and an acidic moiety (such as, but not limited to, carboxylic acid), zwitterions (“internal salts”) can be formed. Such acidic and basic salts used within the scope of the present invention are pharmaceutically acceptable (i.e., non-toxic and physiologically acceptable) salts. Such salts of the compounds of the present invention can be formed, for example, by reacting the compounds of the present invention with a certain amount (such as equivalents) of an acid or base in a medium (such as a medium in which the salt precipitates) or in an aqueous medium, followed by freeze-drying.

[0062] Throughout this specification, where compositions are described as having, including, or containing specific components, or where processes and methods are described as having, including, or containing specific steps, it is contemplated that the invention also includes compositions substantially consisting of or composed of the listed components, and processes and methods substantially consisting of or composed of the listed processing steps.

[0063] Generally, unless otherwise stated, the specified percentages of the composition are by weight.

[0064] I. Heteroaryl compounds One aspect of the present invention provides heteroaryl compounds. These compounds can be used in the pharmaceutical compositions and treatment methods described herein. Exemplary compounds and exemplary procedures for preparing these compounds are described in the following sections.

[0065] One aspect of the present invention provides compounds represented by formula I: (I) Or its pharmaceutically acceptable salt; wherein: A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 5-6-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur; A 2 It is a 4-8 member saturated or partially unsaturated heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5-8 membered saturated bicyclic carbocyclic group, or a covalent bond containing one heteroatom selected from nitrogen and oxygen, wherein the heterocyclic group, monocyclic carbocyclic group, and bicyclic carbocyclic group are separated by 0 or 1 R atoms. 3 replace; A 3 Is it an R that appears 0 or 1 times? 3 Substituted phenylene; R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 alkyl; R 2 Each time it appears, it independently represents halogenation or C. 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 3 Each occurrence independently represents halogenation or C. 1-4 alkyl; Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B-C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 , -C(O)-C(O)-OH, -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl) or -N(R 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl); i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replace; or j) Hydrogen; R 4 It is C 1-6 Hydroxyl group, 3-7 saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, 5-7 bis-oxo-heterocyclic group or 3-7 saturated carbocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups. R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), C 1-6 Alkoxy, -(C 1-6 alkylene)-N(R 1A(R) 1B ) or -(C 1-6 alkylene)-N(R 1A )-C(O)-O-(C 1-6 alkyl); R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl, C 1-4 Halogenated alkyl or -(C 1-4 alkylene)-(C 1-4 Alkyl groups); R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ), -(C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 ; R 8 It is C 1-4 Alkyl or -(C 0-4 alkylene)-(phenyl); R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C 1-4 alkyl); m and n are independently 1 or 2; p is 0, 1, 2, 3 or 4; x is 1, 2, 3, 4, or 5; and y and z are independently 1, 2, or 3; The condition is when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

[0066] The definition of the variable in Formula I above covers multiple chemical groups. This application considers embodiments in which, for example (i) the variable is defined as a single chemical group selected from those chemical groups listed above, (ii) the variable is defined as a set of two or more chemical groups selected from those listed above, and (iii) the compound is defined by a combination of variables, wherein the variable is defined by (i) or (ii).

[0067] In some embodiments, the compound is a compound of formula I.

[0068] As generally defined above, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 5-6-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur.

[0069] In some implementations, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 6-membered heteroaryl ring containing one or two nitrogen heteroatoms.

[0070] In some implementations, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring. In some embodiments, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 5-6 membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur. In some embodiments, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 5-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur. In some embodiments, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur.

[0071] In some implementations, A 1 It is R that appears in p times. 2 Replacement B 1It is a 6-membered aryl ring or a 6-membered heteroaryl ring containing one or two nitrogen heteroatoms. In some embodiments, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or In some implementations, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered heteroaryl ring containing one or two nitrogen heteroatoms. In some embodiments, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered heteroaryl ring containing two nitrogen-containing heteroatoms.

[0072] In some implementations, A 1 It is R that appears in p times. 2 Replacement R appears 1, 2 or 3 times 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement In some implementations, A 1 It is R that appears in p times. 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement In some implementations, A 1 It is R that appears in p times. 2 Replacement Or it may be caused by 1, 2 or 3 R occurrences 2 Replacement .

[0073] In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement R appears 1, 2 or 3 times 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement In some implementations, A 1Is it the 1, 2 or 3 occurrences of R? 2 Replacement R appears 1, 2 or 3 times 2 Replacement .

[0074] In some implementations, A 1 Is it an R that appears 0 or 1 times? 2 Replacement R appears once or twice 2 Replacement It may be caused by one or two occurrences of R. 2 Replacement In some implementations, A 1 Is it an R that appears 0 or 1 times? 2 Replacement Or replaced by one or two .

[0075] In some implementations, A 1 yes , , or Each of them is represented by p occurrences of R. 2 replace.

[0076] In some implementations, A 1 It is R that appears in p times. 2 Replacement In some implementations, A 1 Is it the 2, 3 or 4 occurrences of R? 2 Replacement In some implementations, A 1 Is it one or two Rs that appear? 2 Replacement In some implementations, A 1 It is caused by two Rs appearing. 2 Replacement In some implementations, A 1 It is caused by 3 Rs appearing 2 Replacement In some implementations, A 1 It is caused by 4 Rs appearing 2 Replacement .

[0077] In some implementations, A 1 It is R that appears in p times. 2 Replacement In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2Replacement In some implementations, A 1 Is it an R that appears 0 or 1 times? 2 Replacement In some implementations, A 1 It is R that appears in p times. 2 Replacement In some implementations, A 1 It is R that appears in p times. 2 Replacement .

[0078] In some implementations, A 1 It is R that appears in p times. 2 Replacement In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement In some implementations, A 1 Is it one or two Rs that appear? 2 Replacement In some implementations, A 1 It is caused by 1 occurrence of R 2 Replacement .

[0079] In some implementations, A 1 yes , , , or In some implementations, A 1 yes , , or .

[0080] In some implementations, A 1 yes or In some implementations, A 1 yes or In some implementations, A 1 yes , or In some implementations, A 1 yes or In some implementations, A 1 yes or .

[0081] In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes .

[0082] In some implementations, A 1 yes , , , , , , , , , , , or In some implementations, A 1 yes , , , , , , , , , , or .

[0083] In some implementations, A 1 yes , , , or In some implementations, A 1 yes , , or .

[0084] In some implementations, A 1 yes or In some implementations, A 1 yes or In some implementations, A 1 yes , or In some implementations, A 1 yes or In some implementations, A 1 yes or .

[0085] In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 Selected from the groups depicted in the compounds in Table 1 below.

[0086] As generally defined above, A 2 It is a 4-8 member saturated or partially unsaturated heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5-8 membered saturated bicyclic carbocyclic group, or a covalent bond containing one heteroatom selected from nitrogen and oxygen; wherein the heterocyclic group, monocyclic carbocyclic group, and bicyclic carbocyclic group are separated by 0 or 1 R atoms. 3 replace.

[0087] In some implementations, A 2It is a 6-membered saturated or partially unsaturated heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5-8 membered saturated bicyclic carbocyclic group, or a covalent bond containing one nitrogen atom; wherein the heterocyclic group, monocyclic carbocyclic group, and bicyclic carbocyclic group are separated by 0 or 1 R atoms. 3 replace.

[0088] In some implementations, A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbonyl group, or a 5-8-membered saturated bridged bicyclic carbonyl group containing one nitrogen atom, each of which is separated by 0 or 1 R atoms. 3 Replacement. In some implementations, A 2 It is a 6-membered saturated or partially unsaturated monocyclic subheterocyclic group, a 6-membered saturated or partially unsaturated monocyclic subcarbonyl group, or a 5-8 membered saturated bridged bicyclic subcarbonyl group containing one nitrogen atom.

[0089] In some implementations, A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group containing one nitrogen atom, wherein the heterocyclic group is separated by 0 or 1 R atoms. 3 Replacement. In some implementations, A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group containing one nitrogen atom, wherein the heterocyclic group is characterized by one R-atom. 3 Replacement. In some implementations, A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group containing one nitrogen atom.

[0090] In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 The substituted 6-membered saturated or partially unsaturated monocyclic carbonyl group. In some embodiments, A 2 It is caused by 1 occurrence of R 3 The substituted 6-membered saturated or partially unsaturated monocyclic carbonyl group. In some embodiments, A 2 It is a 6-membered saturated or partially unsaturated monocyclic subcarbonyl group.

[0091] In some implementation schemes, A 2 It is a 4-8 member saturated or partially unsaturated heterocyclic group containing one heteroatom selected from nitrogen and oxygen, wherein the heterocyclic group is separated by 0 or 1 R. 3 replace.

[0092] In some implementation schemes, A 2 Is it an R that appears 0 or 1 times? 3 The substituted 5-8 nucleotide saturated bicyclic subcarbonyl group. In some embodiments, A 2Is it an R that appears 0 or 1 times? 3 Replaced 5-8 nucleotide saturated bridged bicyclic subcarbonyl groups. In some embodiments, A 2 It is caused by 1 occurrence of R 3 Replaced 5-8 nucleotide saturated bridged bicyclic subcarbonyl groups. In some embodiments, A 2 It is a 5-8 saturated bridged bicyclic subcarbonyl group.

[0093] In some implementations, A 2 It is a 5-8 member saturated bridged bicyclic subcarbonyl group or a 5-8 member saturated or partially unsaturated bridged bicyclic subheterocyclic group containing one heteroatom selected from nitrogen and oxygen, each of which is separated by 0 or 1 R. 3 Replacement. In some implementations, A 2 It is a 5-8 member saturated bridged bicyclic subcarbonyl group or a 5-8 member saturated or partially unsaturated bridged bicyclic subheterocyclic group containing one heteroatom selected from nitrogen and oxygen.

[0094] In some implementations, A 2 It is a 5-8 member saturated or partially unsaturated bridged bicyclic subheterocyclic group containing one heteroatom selected from nitrogen and oxygen, wherein the bridged bicyclic subheterocyclic group is separated by 0 or 1 R atoms. 3 Replacement. In some implementations, A 2 It is a 5-8 member saturated or partially unsaturated bridged bicyclic subheterocyclic group containing one heteroatom selected from nitrogen and oxygen, wherein the bridged bicyclic subheterocyclic group is separated by one R. 3 Replacement. In some implementations, A 2 It is a 5-8 member saturated or partially unsaturated bridged bicyclic subheterocyclic group containing one heteroatom selected from nitrogen and oxygen.

[0095] In some implementation schemes, A 2 It includes 4-6 member saturated or partially unsaturated monocyclic heterocyclic groups containing one nitrogen heteroatom, 5-8 member saturated or partially unsaturated bridged bicyclic heterocyclic groups containing one heteroatom selected from oxygen and nitrogen, 6 member saturated or partially unsaturated monocyclic carbonyl groups, and 5-8 member saturated bridged bicyclic carbonyl groups, each of which is separated by 0 or 1 R. 3 Replace; or A 2 It is a covalent bond.

[0096] In some implementations, A 2 It is a 6-membered saturated or partially unsaturated heterocyclic group containing one nitrogen atom, wherein the heterocyclic group is separated by 0 or 1 R atoms. 3 Replacement. In some implementations, A 2 It is a 5-8 nucleotide saturated bicyclic carbocyclic group, wherein the bicyclic carbocyclic group is represented by 0 or 1 R groups. 3Replacement. In some implementations, A 2 It is a covalent bond.

[0097] In some implementations, A 2 yes , , , , , Each of them is represented by 0 or 1 occurrences of R. 3 Replacement. In some implementations, A 2 It is one of the following: a) or , where the nitrogen atom is attached to Z; b) or Where saturated carbon is bonded to Z; or c) or ; Where A 2 R appears 0 or 1 times 3 replace.

[0098] In some implementations, A 2 It is one of the following: a) or , where the nitrogen atom is attached to Z; b) or Where saturated carbon is bonded to Z; or c) or .

[0099] In some implementations, A 2 yes or Each of them is represented by 0 or 1 occurrences of R. 3 Replace, where A 2 The nitrogen atom is bonded to Z. In some embodiments, A 2 yes or A 2 The nitrogen atom is bonded to Z. In some embodiments, A 2 yes or , where saturated carbon is bonded to Z, where A 2 R appears 0 or 1 times 3 Replacement. In some implementations, A 2 yes or , where saturated carbon is bonded to Z. In some embodiments, A 2 yes or Each of them is represented by 0 or 1 occurrences of R. 3 Replacement. In some implementations, A 2 yes or .

[0100] In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement A 2 The nitrogen atom is bonded to Z. In some embodiments, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement A 2 The nitrogen atom is bonded to Z. In some embodiments, A 2 Is it an R that appears 0 or 1 times? 3 Replacement A 2 The saturated carbon is attached to Z.

[0101] In some implementations, A 2 yes In some implementations, A 2 yes In some implementations, A 2 yes In some implementations, A 2 yes A2 The nitrogen atom is bonded to Z. In some embodiments, A 2 yes In some implementations, A 2 yes In some implementations, A 2 yes In some implementations, A 2 yes A 2 The nitrogen atom is bonded to Z. In some embodiments, A 2 yes A 2 The saturated carbon is attached to Z.

[0102] In some implementations, A 2 R appearing 0 times 3 Replacement. In some implementations, A 2 Selected from the groups depicted in the compounds in Table 1 below.

[0103] As generally defined above, A 3 Is it an R that appears 0 or 1 times? 3 Substituted phenylene. In some embodiments, A 3 Is it an R that appears 0 or 1 times? 3 Substituted p-phenylene. In some embodiments, A 3 It is phenylene. In some embodiments, A 3 It is a phenylene oxide. In some embodiments, A 3 yes In some implementations, A 3 Selected from the groups depicted in the compounds in Table 1 below.

[0104] As generally defined above, R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 Alkyl group. In some embodiments, R 1A R 1B and R 1C It is hydrogen. In some implementations, R 1A and R 1B Both are hydrogen. In some implementations, R 1A and R 1B Both are methyl groups. In some embodiments, R 1A It is hydrogen. In some embodiments, R in at least one case 1A It is hydrogen. In some implementations, each R 1A Independently for C 1-4Alkyl group. In some embodiments, R 1B It is hydrogen. In some embodiments, R in at least one case 1B It is hydrogen. In some implementations, each R 1B Independently for C 1-4 Alkyl group. In some embodiments, R 1C It is hydrogen. In some embodiments, R in at least one case 1C It is hydrogen. In some implementations, each R 1C Independently for C 1-4 Alkyl group. In some embodiments, R 1A The groups are selected from those depicted in the compounds listed in Table 1 below. In some embodiments, R 1B The groups are selected from those depicted in the compounds listed in Table 1 below. In some embodiments, R 1C Selected from the groups depicted in the compounds in Table 1 below.

[0105] As generally defined above, R 2 Each time it appears, it independently represents halogenation or C. 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Alkyl or C 1-4 Hydroxyalkyl. In some embodiments, R 2 Each occurrence independently represents fluorination, chlorination, -CF3, -OCH3, -CH3, or -CH2OH. In some embodiments, R 2 Each occurrence independently represents halogenation. In some implementations, each R... 2 It can be fluorinated or chlorinated independently. In some embodiments, R 2 It is fluorinated. In some implementations, R 2 It is chlorinated. In some implementations, R 2 Selected from the groups depicted in the compounds in Table 1 below.

[0106] As generally defined above, R 3 Each occurrence independently represents halogenation or C. 1-4 Alkyl group. In some embodiments, R 3 Each occurrence independently represents halogenation. In some implementations, R 3 Each time it appears, it independently represents C. 1-4 Alkyl group. In some embodiments, R 3 It is fluorinated. In some implementations, R 3 It is chlorinated. In some implementations, R 3 It is methyl. In some embodiments, R 3 Selected from the groups depicted in the compounds in Table 1 below.

[0107] As defined above, Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R)1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 , -C(O)-C(O)-OH, -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation)1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl) or -N(R 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl); i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replace; or j) Hydrogen; The condition is when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

[0108] In some implementations, Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A)-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 -C(O)-C(O)-OH, -C(O)-O-(C1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 or -N(R) 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A)-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl); or i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A replace; The condition is when B 1 Is it an R that appears 0 or 1 times? 2 Substituted 6-membered aryl ring or B 1 It is R that appears 0 times 2 Replacement When Z is not -C(O)R 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

[0109] In some implementations, Z is one of the following: a) -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-O-(C 1-4 alkyl) or -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 Alkyl groups); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 or -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl); c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-OH, -C(O)-OH, -C(O)-O-(C1-6 Alkyl), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B ) or -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 (halogenated alkyl) or -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 ; f) -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl) or -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl); or i) Hydrogen.

[0110] In some implementations, Z is one of the following: a) -C(O)-(C 1-6hydroxyalkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -C(O)-N(R 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl); c) -C(O)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl) or -C(O)-C(O)-(C 1-6 hydroxyalkyl); d) -N(R 1A )-C(O)-C(O)-N(R1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl); f) -N(R 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl) or -N(R) 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 Alkyl); or h) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A replace.

[0111] In some embodiments, Z is selected from the above-mentioned groups, provided that B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is selected from the above-mentioned groups, provided that B... 1Is it an R that appears 0 or 1 times? 2 Substituted 6-membered aryl ring or B 1 It is R that appears 0 times 2 Replacement When Z is not -C(O)-(C 1-6 (hydroxyalkyl).

[0112] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-N(R 1B (R) 1C ), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -N(R) 1A )-C(O)-(C 1-4 alkylene group (5-6 membered saturated heterocyclic group containing 1 oxygen atom), -N(R 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A)-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -N(R 1A )-C(O)-N(R 1B )-[(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy group), -C(O)N(R 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy group, -C(O)-C(O)-OH, -C(O)-C(O)-N(R) 1A (R) 1B ), -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -C(O)-N(R) 1A )-S(O)2-R 7 -N(R) 1A )-S(O)2-R 7 -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy group), -C(O)-C(O)-N(R) 1A )-(C 1-4alkylene)-(5-membered heteroaryl containing 1-4 nitrogen atoms), -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 (Substitution) or hydrogen; condition is when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

[0113] In some implementations, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-7 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl groups and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl groups), -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl containing 1-4 nitrogen atoms), -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 Replacement), -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A )-C(O)-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl), -N(R) 1A )-C(O)-(each of which is controlled by a C1-4 Alkyl groups and a -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl groups), -S(O)2-(C 3-7 Cycloalkyl groups or 5-membered oxo-heterocyclic groups containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is defined by an R 1A replace.

[0114] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R)1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-S(O)2-R 7 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-R 5 -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-R 4 , -C(O)-C(O)-OH, -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B-C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl), -N(R) 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R)1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-S(O)2-R 7 -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-N(R 1B (R) 1C ), -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl); conditions are when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

[0115] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4(alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); conditions are when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

[0116] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); conditions are when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

[0117] In some implementations, Z is -C(O)-(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (Cycloalkyl). In some embodiments, Z is -C(O)-(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); conditions are when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)-(C 1-6 (hydroxyalkyl).

[0118] In some implementations, Z is -C(O)R 4 or -C(O)-(C 1-4 (alkylene)-R 4 In some implementations, Z is -C(O)R 4 or -C(O)-(C 1-4 (alkylene)-R 4 Condition B 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring.

[0119] In some implementations, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C1-6 alkoxy), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (Cycloalkyl). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (cycloalkyl).

[0120] In some implementations, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4-C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (Cycloalkyl). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 alkyl) or -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 In some implementations, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 alkyl) or -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (Cycloalkyl). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-O-(C 1-4 alkyl) or -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6Alkoxy group). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (cycloalkyl).

[0121] In some implementations, Z is -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 .

[0122] In some implementations, Z is -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A)-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl) or -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 (cycloalkyl).

[0123] In some implementations, Z is -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -C(O)-N(R 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl).

[0124] In some implementations, Z is -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 alkyl) or -C(O)-N(R 1A )-(C 1-4 (Haloalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 .

[0125] In some implementations, Z is -C(O)-C(O)-N(R) 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 , -C(O)-C(O)-OH, -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace).

[0126] In some implementations, Z is -C(O)-C(O)-N(R) 1A )-R 5 -C(O)-C(O)-N(R) 1A (R)1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 -C(O)-C(O)-OH, -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace).

[0127] In some implementations, -C(O)-C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl) or -C(O)-C(O)-(C 1-6 (hydroxyalkyl).

[0128] In some implementations, Z is -C(O)-C(O)-N(R) 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl) or -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 Or -C(O)-C(O)-OH. In some embodiments, Z is -C(O)-C(O)-N(R) 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl) or -C(O)-C(O)-N(R) 1A )-(C 1-4 Alkylene group (5-membered heteroaryl group containing 1-4 nitrogen atoms).

[0129] In some implementations, Z is -C(O)-C(O)-R 4 Or -C(O)-C(O)-OH. In some embodiments, Z is -C(O)-OH or -C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace).

[0130] In some implementations, Z is -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A)-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 Alkyl group). In some embodiments, Z is -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl).

[0131] In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R)1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl).

[0132] In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 (halogenated alkyl) or -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl).

[0133] In some implementations, Z is -N(R) 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A)-C(O)-O-(C 1-4 alkylene)-(phenyl) or -N(R 1A )-S(O)2-R 7 .

[0134] In some implementations, Z is -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 or -N(R) 1A )-S(O)2-R 7 In some implementations, Z is -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl) or -N(R) 1A )-S(O)2-R 7 In some implementations, Z is -N(R) 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl) or -N(R 1A )-C(O)-O-(C 1-4 (alkylene)-(phenyl).

[0135] In some implementations, Z is -N(R) 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl) or -N(R) 1A )-C(O)-(C 1-4 (alkylene)-(tetrahydrofuranyl or tetrahydropyranyl). In some embodiments, Z is -N(R 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl) or -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 In some implementations, Z is -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 or -N(R) 1A )-C(O)-O-(C 1-4 (alkylene)-(phenyl).

[0136] In some implementations, Z is -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A)-C(O)-N(R 1B (R) 1C In some implementations, Z is -S(O)2-(C). 1-6 hydroxyalkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C In some implementations, Z is -S(O)2-(C). 1-6 alkyl) or -S(O)2-(C 3-7 (cycloalkyl).

[0137] In some implementations, Z is -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 or -S(O)2-(C3-7 (Cycloalkyl). In some embodiments, Z is -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl) or -S(O)2-N(R 1A (R) 1B In some implementations, Z is -S(O)2-N(R). 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ).

[0138] In some implementations, Z is -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-[(C 1-4 [alkylene]-O-] x -(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 alkyl).

[0139] In some implementations, Z is -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl).

[0140] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl), -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-S(O)2-R 7 -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl group or a 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replacement; condition is when B 1 Is it an R that appears 0 or 1 times? 2When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl), -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-6 hydroxyalkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -S(O)2-N(R 1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 Alkyl); conditions are when B 1 Is it an R that appears 0 or 1 times? 2When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 .

[0141] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 and -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 and -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 Hydroxyalkyl); conditions are when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 .

[0142] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4Alkyl), -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl) or -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl) or -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 Hydroxyalkyl); conditions are when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 .

[0143] In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl) or -N(R 1A )-C(O)-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -N(R 1A )-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl) or -N(R 1A )-C(O)-(C 1-6 (hydroxyalkyl).

[0144] In some implementations, Z is -C(O)R 4 In some implementations, Z is -C(O)R 4 The condition is B. 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring. In some embodiments, Z is -C(O)-(C1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-(C 1-6 Hydroxyalkyl), under condition B 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring. In some embodiments, Z is -C(O)-(C 1-4 (alkylene)-R 4 In some implementations, Z is -C(O)-(C 1-4 (alkylene)-R 4 The condition is B. 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring.

[0145] In some implementations, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 In some implementations, Z is -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 (Cycloalkyl). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C replaced by a -OH group) 3-8 (Cycloalkyl). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 5-8 Bridged bicyclic cycloalkyl groups). In some embodiments, Z is -C(O)- (wherein each is separated by a C).1-4 Alkyl and an -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl group. In some embodiments, Z is -C(O)- (substituted with a -N(R)-). 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (Cycloalkyl). In some embodiments, Z is -C(O)- (intercalated by a -N(R)-). 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) co-substituted C 3-7 (cycloalkyl).

[0146] In some implementations, Z is -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-(C replaced by one halogenated group) 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1A (R) 1B In some implementations, Z is -C(O)-N(R). 1A )-(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A )-(C 1-4 (Haloalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A )-[(C1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B In some implementations, Z is -C(O)-N(R). 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 In some implementations, Z is -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A )-(C 0-4 (alkylene)-(tetrahydrofuranyl or tetrahydropyranyl). In some embodiments, Z is -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 (Cycloalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-S(O)2-R 7 .

[0147] In some implementations, Z is -C(O)-C(O)-N(R) 1A )-R 5 In some implementations, Z is -C(O)-C(O)-N(R) 1A )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -C(O)-C(O)-N(R 1A (R) 1BIn some implementations, Z is -C(O)-C(O)-N(R). 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-C(O)-N(R) 1A )-(C 1-4 Alkylene group (a 5-membered heteroaryl group containing 1-4 nitrogen atoms). In some embodiments, Z is -C(O)-C(O)-R 4 In some implementations, Z is -C(O)-C(O)-OH.

[0148] In some embodiments, Z is -C(O)-OH. In some embodiments, Z is -C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B In some implementations, Z is -C(O)-O-(with one occurrence of -N(R)). 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 Hydroxyalkyl). In some embodiments, Z is -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace).

[0149] In some implementations, Z is -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -N(R 1A )-C(O)-C(O)-N(R 1B (R) 1C In some implementations, Z is -N(R). 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -N(R)1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl).

[0150] In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 Hydroxyalkyl). In some embodiments, Z is -N(R 1A )-C(O)-N(R 1B )-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -N(R 1A )-C(O)-N(R 1B (R) 1C In some implementations, Z is -N(R). 1A )-C(O)-N(R 1B )-(C 1-4 (Haloalkyl). In some embodiments, Z is -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 (alkylene)-(tetrahydrofuranyl or tetrahydropyranyl). In some embodiments, Z is -N(R 1A Z is -C(O)-(morpholinyl). In some embodiments, Z is -N(R 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl).

[0151] In some implementations, Z is -N(R) 1A )-C(O)-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -N(R 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B)-S(O)2-(C 1-4 Alkyl group). In some embodiments, Z is -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 In some implementations, Z is -N(R) 1A )-C(O)-O-(C 1-4 (alkylene)-(phenyl). In some embodiments, Z is -N(R 1A )-C(O)-(C 1-4 (alkylene)-(tetrahydrofuranyl or tetrahydropyranyl). In some embodiments, Z is -N(R 1A )-S(O)2-R 7 In some implementations, Z is -N(R) 1A )-S(O)2-(C 0-4 alkylene)-N(R 1A (R) 1B In some implementations, Z is -N(R). 1A )-S(O)2-(C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -N(R) 1A )-S(O)2-N(R 1B )-C(O)-OR 8 In some implementations, Z is -N(R) 1A )-S(O)2-N(R 1B )-CO2-(C 1-4 (alkylene)-(phenyl).

[0152] In some implementations, Z is -S(O)2-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -S(O)2-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-(C 1-4 alkylene)-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 In some implementations, Z is -S(O)2-[(C 1-4 [alkylene]-O-] x -(C1-6 Alkyl group). In some embodiments, Z is -S(O)2-(C 3-7 (Cycloalkyl). In some embodiments, Z is -S(O)2-N(R 1A )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -S(O)2-N(R 1A (R) 1B In some implementations, Z is -S(O)2-N(R). 1A )-C(O)-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-N(R) 1A )-C(O)-N(R 1B (R) 1C ).

[0153] In some implementations, Z is -(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -(C 1-4 (alkylene)-C(O)-OH. In some embodiments, Z is -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl).

[0154] In some embodiments, Z is a 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replacement. In some implementations, Z is replaced by a C. 1-4 Alkyl-substituted oxazolidinone or imidazolidinone. In some embodiments, Z is hydrogen.

[0155] In some implementations, Z is , , , , , , , , , , , , , , , , , , , , , , , , , , , or .

[0156] In some implementations, Z is , , , , , , , , , , , , , , , , , , , , , , or .

[0157] In some implementations, Z is , , , , , , , , , , , , , , , , , , , , , or In some implementations, Z is , , , , , , , , , , , , , , , , , , , , , or The condition is when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not... .

[0158] In some implementations, Z is , , , , , , , , or The condition is when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not... In some implementations, Z is , , or The condition is when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not... .

[0159] In some implementations, Z is , , , , or The condition is when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not... In some implementations, Z is , or The condition is when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not... In some implementations, Z is , , , or In some implementations, Z is or In some implementations, Z is , or .

[0160] In some implementations, Z is , , , , , , , , or In some implementations, Z is , , , or In some implementations, Z is , or In some implementations, Z is , or In some implementations, Z is , , or In some implementations, Z is or .

[0161] In some implementations, Z is , , or In some implementations, Z is , , , , , , or In some implementations, Z is , , or .

[0162] In some implementations, Z is In some implementations, Z is The condition is B. 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring. In some embodiments, Z is... In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is The condition is B. 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring. In some embodiments, Z is... In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is .

[0163] In some implementations, Z is , , , , , or In some implementations, Z is , , , , , , , , , , , , , , , , , or In some implementations, Z is , , , , , , , , or In some implementations, Z is , , , , , , , , , , , , , , or In some implementations, Z is , , , , , , , , , , , or In some implementations, Z is , , , , , or In some implementations, Z is , , , , , , , or In some implementations, Z is or .

[0164] In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is .

[0165] The above text discusses the presence of -C(O)R. 4 -C(O)-(C 1-4 (alkylene)-R 4 and / or -C(O)-(C 1-6 In certain implementations of the variable Z (hydroxyalkyl), it is specified that when B 1 Is it an R that appears 0 or 1 times? 2 Substituted 6-membered aryl ring or B 1 It is R that appears 0 times 2 Replacement When Z is not -C(O)R 4 -C(O)-(C 1-6 hydroxyalkyl) or -C(O)-(C 1-4 (alkylene)-R 4 .

[0166] In some embodiments, Z is selected from the groups depicted in the compounds in Table 1 below.

[0167] As generally defined above, R 4 It is C 1-6 Hydroxyl group, 3-7 saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, 5-7 bis-oxo-heterocyclic group or 3-7 saturated carbocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups.

[0168] In some implementation schemes, R 4 It is a 3-7 membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, a 5-7 membered di-oxo-heterocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, or a 3-7 membered saturated carbocyclic group, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups.

[0169] In some implementations, R 4 It is C 1-6 Hydroxyl alkyl, a 3-7 membered saturated heterocyclic group or a 3-7 membered saturated carbocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by one or more hydroxyl groups. In some embodiments, R 4 It is C 1-6 Hydroxyalkyl. In some embodiments, R 4It is a 3-7 membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 3-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 4-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 5-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 6-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or two hydroxyl groups. In some embodiments, R 4 It is a 7-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 3-7 member saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 3-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 4-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 5-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 6-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 7-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 5-7 membered di-oxo-heterocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen, and oxygen. In some embodiments, R 4 Selected from the groups depicted in the compounds in Table 1 below.

[0170] As generally defined above, R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), C 1-6 Alkoxy, -(C 1-6 alkylene)-N(R 1A (R)1B ) or -(C 1-6 alkylene)-N(R 1A )-C(O)-O-(C 1-6 Alkyl group). In some embodiments, R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy) or C 1-6 Alkyl group. In some embodiments, R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl or C 1-6 Alkyl group. In some embodiments, R 5 It is C 1-6 Alkyl group. In some embodiments, R 5 Yes -CH3. In some implementations, R 5 It is C 1-6 Hydroxyalkyl. In some embodiments, R 5 It is C 1-6 Alkyl group. In some embodiments, R 5 Yes - (C 1-4 alkylene)-(C 1-4 alkoxy) or -(C 1-6 alkylene)-N(R 1A (R) 1B In some implementations, R 5 Yes - (C 1-4 alkylene)-(C 1-4 Alkyl group). In some embodiments, R 5 Yes - (C 1-6 alkylene)-N(R 1A (R) 1B In some implementations, R 5 Yes - (C 1-6 alkylene)-N(R 1A )-C(O)-O-(C 1-6 Alkyl). In some embodiments, R 5 Selected from the groups depicted in the compounds in Table 1 below.

[0171] As generally defined above, R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl, C 1-4 Halogenated alkyl or -(C 1-4 alkylene)-(C 1-4 Alkyl group). In some embodiments, R 6 It is C 1-4Alkyl, C 1-4 Hydroxyalkyl or C 1-4 Halogenated alkyl groups. In some embodiments, R 6 It is C 1-4 Alkyl group. In some embodiments, R 6 Yes -CH3. In some implementations, R 6 It is C 1-4 Hydroxyalkyl. In some embodiments, R 6 It is C 1-4 Halogenated alkyl groups. In some embodiments, R 6 Yes - (C 1-4 alkylene)-(C 1-4 Alkyl group). In some embodiments, R 6 Selected from the groups depicted in the compounds in Table 1 below.

[0172] As generally defined above, R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ), -(C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 In some implementations, R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy or C 1-6 Hydroxyalkyl. In some embodiments, R 7 Yes - (C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ), -(C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 In some implementations, R 7 Yes - (C 0-4 alkylene)-N(R 1A (R) 1B ), -(C 0-6alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 In some implementations, R 7 It is -N(R) 1A (R) 1B ), -N(R 1B )-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 In some implementations, R 7 Yes - (C 1-4 alkylene)-N(R 1A (R) 1B ) or -(C 1-6 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl group). In some embodiments, R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ) or -N(R 1B )-C(O)-OR 8 In some implementations, R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, -(C 0-4 alkylene)-N(R 1A (R) 1B ) or -N(R 1B )-C(O)-OR 8 .

[0173] In some implementations, R 7 It is C 1-4 Alkyl group. In some embodiments, R 7 Yes -CH3. In some implementations, R 7 It is C 1-4 Alkyl group. In some embodiments, R 7 It is C 1-6 Hydroxyalkyl. In some embodiments, R 7 Yes - (C 0-4 alkylene)-N(R 1A (R) 1B In some implementations, R7 It is -N(R) 1A (R) 1B In some implementations, R 7 Yes - (C 1-4 alkylene)-N(R 1A (R) 1B In some implementations, R 7 It is -N(R) 1B )-C(O)-OR 8 In some implementations, R 7 Yes - (C 1-4 alkylene)-(C 1-4 Alkyl group). In some embodiments, R 7 Yes - (C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl). In some embodiments, R 7 It is -N(R) 1B )-C(O)-(C 1-4 Alkyl). In some embodiments, R 7 Yes - (C 1-6 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl). In some embodiments, R 7 Selected from the groups depicted in the compounds in Table 1 below.

[0174] As generally defined above, R 8 It is C 1-4 Alkyl or -(C 0-4 (alkylene)-(phenyl). In some embodiments, R 8 It is C 1-4 Alkyl group. In some embodiments, R 8 Yes -CH3. In some implementations, R 8 Yes - (C 0-4 (alkylene)-(phenyl). In some embodiments, R 8 Selected from the groups depicted in the compounds in Table 1 below.

[0175] As generally defined above, R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C 1-4 Alkyl). In some embodiments, R 9 It is an oxidation process. In some implementations, R... 9 It is C 1-4 Alkyl group. In some embodiments, R 9 Yes -CH3. In some implementations, R9 It is a hydroxyl group. In some embodiments, R 9 It is -C(O)-O-(C 1-4 Alkyl). In some embodiments, R 9 Selected from the groups depicted in the compounds in Table 1 below.

[0176] As generally defined above, m and n are independently 1 or 2. In some embodiments, m and n are 1. In some embodiments, m is 1. In some embodiments, m is 2. In some embodiments, n is 1. In some embodiments, n is 2. In some embodiments, m is selected from the values ​​shown in the compounds in Table 1 below. In some embodiments, n is selected from the values ​​shown in the compounds in Table 1 below.

[0177] As generally defined above, p is 0, 1, 2, 3, or 4. In some embodiments, p is 0. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is 0 or 1. In some embodiments, p is 1 or 2. In some embodiments, p is 2 or 3. In some embodiments, p is 3 or 4. In some embodiments, p is 0, 1, or 2. In some embodiments, p is 1, 2, or 3. In some embodiments, p is 2, 3, or 4. In some embodiments, p is 0, 1, 2, or 3. In some embodiments, p is 1, 2, 3, or 4. In some embodiments, p is selected from the values ​​shown for the compounds in Table 1 below.

[0178] As generally defined above, x is 1, 2, 3, 4, or 5. In some embodiments, x is 1. In some embodiments, x is 2. In some embodiments, x is 3. In some embodiments, x is 4. In some embodiments, x is 5. In some embodiments, x is selected from the values ​​shown for the compounds in Table 1 below.

[0179] As generally defined above, y and z are independently 1, 2, or 3. In some embodiments, y is 1. In some embodiments, y is 2. In some embodiments, y is 3. In some embodiments, y is selected from the values ​​shown in the compounds in Table 1 below. In some embodiments, z is 1. In some embodiments, z is 2. In some embodiments, z is 3. In some embodiments, z is selected from the values ​​shown in the compounds in Table 1 below.

[0180] The foregoing describes several embodiments involving compounds of Formula I. This patent application specifically covers all combinations of the described embodiments.

[0181] Another aspect of the present invention provides compounds represented by formula IB: (IB) Or its pharmaceutically acceptable salt; wherein: A 1 It is R that appears in p times. 2 Replacement R appears 1, 2 or 3 times 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement ; A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbocyclic group, or a 5-8-membered saturated bridged bicyclic carbocyclic group containing one nitrogen atom, wherein the heterocyclic group, monocyclic carbocyclic group, and bicyclic carbocyclic group are separated by 0 or 1 R atoms. 3 replace; R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 alkyl; R 2 Each time it appears, it independently represents halogenation or C. 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 3 Is it halogenated or C 1-4 alkyl; Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C1-6 alkoxy), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A)-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 , -C(O)-C(O)-OH, -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl) or -N(R 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl); i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replace; or j) Hydrogen; R 4 It is C 1-6 Hydroxyl group, 3-7 saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, 5-7 bis-oxo-heterocyclic group or 3-7 saturated carbocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups. R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), C 1-6 Alkoxy, -(C 1-6 alkylene)-N(R 1A (R) 1B ) or -(C 1-6 alkylene)-N(R 1A )-C(O)-O-(C 1-6 alkyl); R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl, C 1-4 Halogenated alkyl or -(C 1-4 alkylene)-(C 1-4 Alkyl groups); R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ), -(C 0-6 alkylene)-N(R 1B)-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 ; R 8 It is C 1-4 Alkyl or -(C 0-4 alkylene)-(phenyl); R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C 1-4 alkyl); p is 0, 1, 2, 3 or 4; x is 1, 2, 3, 4, or 5; and y and z are 1, 2 or 3 independently.

[0182] In the above formula IB, the definition of a variable covers multiple chemical groups. This application considers embodiments in which, for example (i) the variable is defined as a single chemical group selected from those chemical groups listed above, (ii) the variable is defined as a collection of two or more chemical groups selected from those listed above, and (iii) the compound is defined by a combination of variables, wherein the variable is defined by (i) or (ii).

[0183] In some embodiments, the compound is a compound of formula IB.

[0184] As generally defined above, A 1 It is R that appears in p times. 2 Replacement R appears 1, 2 or 3 times 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement In some implementations, A 1 It is R that appears in p times. 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement In some implementations, A 1 It is R that appears in p times. 2 Replacement Or it may be caused by 1, 2 or 3 R occurrences 2 Replacement .

[0185] In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement R appears 1, 2 or 3 times 2Replacement Or by 2, 3 or 4 R occurrences 2 Replacement In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement R appears 1, 2 or 3 times 2 Replacement .

[0186] In some implementations, A 1 It is R that appears in p times. 2 Replacement In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement In some implementations, A 1 Is it an R that appears 0 or 1 times? 2 Replacement .

[0187] In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement In some implementations, A 1 Is it one or two Rs that appear? 2 Replacement In some implementations, A 1 It is caused by 1 occurrence of R 2 Replacement .

[0188] In some implementations, A 1 Is it the 2, 3 or 4 occurrences of R? 2 Replacement In some implementations, A 1 It is caused by two Rs appearing. 2 Replacement In some implementations, A 1 It is caused by 3 Rs appearing 2 Replacement In some implementations, A 1 It is caused by 4 Rs appearing 2 Replacement .

[0189] In some implementations, A 1 yes , , , or In some implementations, A 1 yes , , or .

[0190] In some implementations, A 1 yes or In some implementations, A 1 yes , or In some implementations, A 1 yes or In some implementations, A 1 yes or .

[0191] In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes .

[0192] In some implementations, A 1 yes , , , or In some implementations, A 1 yes , , or .

[0193] In some implementations, A 1 yes or In some implementations, A 1 yes , or In some implementations, A 1 yes or In some implementations, A 1 yes or .

[0194] In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes .

[0195] As generally defined above, A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbocyclic group, or a 5-8-membered saturated bridged bicyclic carbocyclic group containing one nitrogen atom, wherein the heterocyclic group, monocyclic carbocyclic group, and bicyclic carbocyclic group are separated by 0 or 1 R atoms. 3 replace.

[0196] In some implementations, A 2 It is a 6-membered saturated or partially unsaturated monocyclic subheterocyclic group, a 6-membered saturated or partially unsaturated monocyclic subcarbonyl group, or a 5-8 membered saturated bridged bicyclic subcarbonyl group containing one nitrogen atom.

[0197] In some implementations, A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group containing one nitrogen atom, wherein the heterocyclic group is separated by 0 or 1 R atoms. 3 Replacement. In some implementations, A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group containing one nitrogen atom, wherein the heterocyclic group is characterized by one R-atom. 3 Replacement. In some implementations, A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group containing one nitrogen atom.

[0198] In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 The substituted 6-membered saturated or partially unsaturated monocyclic carbonyl group. In some embodiments, A2 It is caused by 1 occurrence of R 3 The substituted 6-membered saturated or partially unsaturated monocyclic carbonyl group. In some embodiments, A 2 It is a 6-membered saturated or partially unsaturated monocyclic subcarbonyl group.

[0199] In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replaced 5-8 nucleotide saturated bridged bicyclic subcarbonyl groups. In some embodiments, A 2 It is caused by 1 occurrence of R 3 Replaced 5-8 nucleotide saturated bridged bicyclic subcarbonyl groups. In some embodiments, A 2 It is a 5-8 saturated bridged bicyclic subcarbonyl group.

[0200] In some implementations, A 2 yes , , , , , Each of them is represented by 0 or 1 occurrences of R. 3 Replacement. In some implementations, A 2 It is one of the following: a) or , where the nitrogen atom is attached to Z; b) or Where saturated carbon is bonded to Z; or c) or ; Where A 2 R appears 0 or 1 times 3 replace.

[0201] In some implementations, A 2 It is one of the following: a) or , where the nitrogen atom is attached to Z; b) or Where saturated carbon is bonded to Z; or c) or .

[0202] In some implementations, A 2 yes or Each of them is represented by 0 or 1 occurrences of R. 3 Replace, where A2 The nitrogen atom is bonded to Z. In some embodiments, A 2 yes or A 2 The nitrogen atom is bonded to Z. In some embodiments, A 2 yes or , where saturated carbon is bonded to Z, where A 2 R appears 0 or 1 times 3 Replacement. In some implementations, A 2 yes or , where saturated carbon is bonded to Z. In some embodiments, A 2 yes or Each of them is represented by 0 or 1 occurrences of R. 3 Replacement. In some implementations, A 2 yes or .

[0203] In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement A 2 The nitrogen atom is bonded to Z. In some embodiments, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement A 2 The saturated carbon is attached to Z.

[0204] In some implementations, A 2 yes In some implementations, A 2yes In some implementations, A 2 yes In some implementations, A 2 yes A 2 The nitrogen atom is bonded to Z. In some embodiments, A 2 yes In some implementations, A 2 yes In some implementations, A 2 yes A 2 The saturated carbon is bonded to Z. In some embodiments, A 2 R appearing 0 times 3 replace.

[0205] As generally defined above, R 3 Is it halogenated or C 1-4 Alkyl group. In some embodiments, R 3 It is halogenated. In some implementations, R 3 It is C 1-4 Alkyl group. In some embodiments, R 3 It is a methyl group.

[0206] In some implementations, variable R 1A , R 1B , R 1C , R 2 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 The definition of each of p, x, y, z, and Z is one of the implementation schemes described in combination I above.

[0207] The foregoing describes several embodiments of compounds relating to formula IB. This patent application specifically covers all combinations of the described embodiments.

[0208] Another aspect of the present invention provides compounds represented by formula IC: (IC) Or its pharmaceutically acceptable salt; wherein: A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 6-membered heteroaryl ring containing one or two nitrogen atoms; A 2 It is a 5-8 member saturated bridged bicyclic carbocyclic group or a 5-8 member saturated or partially unsaturated bridged bicyclic heterocyclic group containing one heteroatom selected from nitrogen and oxygen, wherein the bicyclic carbocyclic group and the heterocyclic group are separated by 0 or 1 R. 3 replace; R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 alkyl; R 2 Each time it appears, it independently represents halogenation or C. 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 3 Is it halogenated or C 1-4 alkyl; Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R)1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 , -C(O)-C(O)-OH, -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R)1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl) or -N(R 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl); i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replace; or j) Hydrogen; R 4 It is C 1-6 Hydroxyl group, 3-7 saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, 5-7 bis-oxo-heterocyclic group or 3-7 saturated carbocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups. R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), C 1-6 Alkoxy, -(C 1-6 alkylene)-N(R 1A (R) 1B ) or -(C 1-6 alkylene)-N(R 1A )-C(O)-O-(C 1-6 alkyl); R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl, C 1-4 Halogenated alkyl or -(C 1-4 alkylene)-(C 1-4 Alkyl groups); R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ), -(C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 ; R 8 It is C 1-4 Alkyl or -(C 0-4 alkylene)-(phenyl); R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C1-4 alkyl); p is 0, 1, 2, 3 or 4; x is 1, 2, 3, 4, or 5; and y and z are 1, 2 or 3 independently.

[0209] In the above formula IC, the definition of a variable covers multiple chemical groups. This application contemplates embodiments in which, for example (i) the variable is defined as a single chemical group selected from those chemical groups listed above, (ii) the variable is defined as a collection of two or more chemical groups selected from those listed above, and (iii) the compound is defined by a combination of variables, wherein the variable is defined by (i) or (ii).

[0210] In some embodiments, the compound is a compound of formula IC.

[0211] As generally defined above, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 6-membered heteroaryl ring containing one or two nitrogen heteroatoms.

[0212] In some implementations, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or In some implementations, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered heteroaryl ring containing one or two nitrogen heteroatoms. In some embodiments, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered heteroaryl ring containing two nitrogen-containing heteroatoms.

[0213] In some implementations, A 1 It is R that appears in p times. 2 Replacement R appears 1, 2 or 3 times 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement In some implementations, A 1 It is R that appears in p times. 2 Replacement Or by 2, 3 or 4 R occurrences2 Replacement In some implementations, A 1 It is R that appears in p times. 2 Replacement Or it may be caused by 1, 2 or 3 R occurrences 2 Replacement .

[0214] In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement R appears 1, 2 or 3 times 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement R appears 1, 2 or 3 times 2 Replacement .

[0215] In some implementations, A 1 Is it an R that appears 0 or 1 times? 2 Replacement R appears once or twice 2 Replacement It may be caused by one or two occurrences of R. 2 Replacement In some implementations, A 1 Is it an R that appears 0 or 1 times? 2 Replacement Or replaced by one or two .

[0216] In some implementations, A 1 It is R that appears in p times. 2 Replacement In some implementations, A 1 It is either R that appears 2, 3, or 4 times. 2 Replacement In some implementations, A 1 Is it one or two Rs that appear? 2 Replacement In some implementations, A1 Is or is two occurrences of R 2 Replacement In some implementations, A 1 It is caused by 3 Rs appearing 2 Replacement In some implementations, A 1 It is caused by 4 Rs appearing 2 Replacement .

[0217] In some implementations, A 1 It is R that appears in p times. 2 Replacement In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement In some implementations, A 1 Is it an R that appears 0 or 1 times? 2 Replacement .

[0218] In some implementations, A 1 It is R that appears in p times. 2 Replacement In some implementations, A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement In some implementations, A 1 Is it one or two Rs that appear? 2 Replacement In some implementations, A 1 It is caused by 1 occurrence of R 2 Replacement .

[0219] In some implementations, A 1 yes , , , or In some implementations, A 1 yes , , or .

[0220] In some implementations, A 1 yes or In some implementations, A 1 yes or In some implementations, A 1 yes , or In some implementations, A 1 yes or In some implementations, A 1 yes or .

[0221] In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes .

[0222] In some implementations, A 1 yes , , , , , , , , , , or .

[0223] In some implementations, A 1 yes , , , or In some implementations, A 1 yes , , or .

[0224] In some implementations, A 1 yes or In some implementations, A 1 yes or In some implementations, A 1 yes , or In some implementations, A 1 yes or In some implementations, A 1 yes or .

[0225] In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes .

[0226] As generally defined above, A 2 It is a 5-8 member saturated bridged bicyclic carbocyclic group or a 5-8 member saturated or partially unsaturated bridged bicyclic heterocyclic group containing one heteroatom selected from nitrogen and oxygen, wherein the bicyclic carbocyclic group and the heterocyclic group are separated by 0 or 1 R. 3 Replacement. In some implementations, A 2 It is a 5-8 member saturated bridged bicyclic subcarbonyl group or a 5-8 member saturated or partially unsaturated bridged bicyclic subheterocyclic group containing one heteroatom selected from nitrogen and oxygen.

[0227] In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replaced 5-8 nucleotide saturated bridged bicyclic subcarbonyl groups. In some embodiments, A 2 It is caused by 1 occurrence of R 3Replaced 5-8 nucleotide saturated bridged bicyclic subcarbonyl groups. In some embodiments, A 2 It is a 5-8 saturated bridged bicyclic subcarbonyl group.

[0228] In some implementations, A 2 It is a 5-8 member saturated or partially unsaturated bridged bicyclic subheterocyclic group containing one heteroatom selected from nitrogen and oxygen, wherein the bridged bicyclic subheterocyclic group is separated by 0 or 1 R atoms. 3 Replacement. In some implementations, A 2 It is a 5-8 member saturated or partially unsaturated bridged bicyclic subheterocyclic group containing one heteroatom selected from nitrogen and oxygen, wherein the bridged bicyclic subheterocyclic group is separated by one R. 3 Replacement. In some implementations, A 2 It is a 5-8 member saturated or partially unsaturated bridged bicyclic subheterocyclic group containing one heteroatom selected from nitrogen and oxygen.

[0229] In some implementations, A 2 yes or Each of them is represented by 0 or 1 occurrences of R. 3 Replacement. In some implementations, A 2 yes or In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement A 2 The nitrogen atom is bonded to Z. In some embodiments, A 2 yes In some implementations, A 2 yes In some implementations, A 2 yes In some implementations, A 2 yes A 2 The nitrogen atom is attached to Z.

[0230] In some implementations, A 2R appearing 0 times 3 replace.

[0231] As generally defined above, R 3 Is it halogenated or C 1-4 Alkyl group. In some embodiments, R 3 It is halogenated. In some implementations, R 3 It is C 1-4 Alkyl group. In some embodiments, R 3 It is a methyl group.

[0232] As defined above, Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A(R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 , -C(O)-C(O)-OH, -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R6 -N(R) 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl) or -N(R 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl); i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replace; or j) Hydrogen.

[0233] In some implementations, Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R)1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R)1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 -C(O)-C(O)-OH, -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-]x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 or -N(R) 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl); or i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A replace.

[0234] In some implementations, Z is one of the following: a) -C(O)-(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -C(O)-N(R 1A)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl); c) -C(O)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl) or -C(O)-C(O)-(C 1-6 hydroxyalkyl); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl); f) -N(R 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl) or -N(R) 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A )-(C1-6 hydroxyalkyl), -S(O)2-N(R 1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 Alkyl); or h) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A replace.

[0235] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (cycloalkyl).

[0236] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (cycloalkyl).

[0237] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl), -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-C(O)-N(R)1A )-R 5 -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-S(O)2-R 7 -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl group or a 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replacement. In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl), -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R)1A )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-6 hydroxyalkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -S(O)2-N(R 1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 alkyl).

[0238] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 and -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 1-6hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl) or -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 (hydroxyalkyl).

[0239] In some implementations, the variable Z is defined as one of the implementations described above with respect to Equation I. In some implementations, the variable Z is defined as one of the implementations described below in conjunction with Equation ID.

[0240] In some implementations, variable R 1A R 1B R 1C R 2 R 4 R 5 R 6 R 7 R 8 R 9 The definition of each of p, x, y, and z is one of the implementation schemes described in the above-mentioned combination formula I.

[0241] The foregoing describes several embodiments of compounds relating to formula IC. This patent application specifically covers all combinations of the described embodiments.

[0242] Another aspect of the present invention provides compounds represented by formula ID: (ID) Or its pharmaceutically acceptable salt; wherein: A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 6-membered heteroaryl ring containing one or two nitrogen atoms; A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbocyclic group, or a 5-8-membered saturated bridged bicyclic carbocyclic group containing one nitrogen atom, wherein the heterocyclic group, monocyclic carbocyclic group, and bicyclic carbocyclic group are separated by 0 or 1 R atoms. 3 replace; R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 alkyl; R 2 Each time it appears, it independently represents halogenation or C.1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 3 Is it halogenated or C 1-4 alkyl; Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R)1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 -C(O)-C(O)-OH, -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R)1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 or -N(R) 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl); or i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A replace; R 4 It is C 1-6 Hydroxyl group, 3-7 saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, 5-7 bis-oxo-heterocyclic group or 3-7 saturated carbocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups. R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), C 1-6 Alkoxy, -(C 1-6 alkylene)-N(R 1A (R) 1B ) or -(C 1-6 alkylene)-N(R 1A )-C(O)-O-(C 1-6 alkyl); R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl, C 1-4 Halogenated alkyl or -(C 1-4 alkylene)-(C 1-4 Alkyl groups); R 7 It is C 1-4 Alkyl, C 1-4Alkoxy, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ), -(C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 ; R 8 It is C 1-4 Alkyl or -(C 0-4 alkylene)-(phenyl); R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C 1-4 alkyl); p is 0, 1, 2, 3 or 4; x is 1, 2, 3, 4, or 5; and z is 1, 2, or 3; The condition is when B 1 Is it an R that appears 0 or 1 times? 2 Substituted 6-membered aryl ring or B 1 It is R that appears 0 times 2 Replacement When Z is not -C(O)R 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

[0243] The definition of the variable in the above formula ID covers multiple chemical groups. This application considers embodiments in which, for example (i) the variable is defined as a single chemical group selected from those chemical groups listed above, (ii) the variable is defined as a set of two or more chemical groups selected from those listed above, and (iii) the compound is defined by a combination of variables, wherein the variable is defined by (i) or (ii).

[0244] In some embodiments, the compound is a compound of formula ID.

[0245] In some implementations, variable A 1 The definition is one of the implementation schemes described above for the combined IC.

[0246] In some implementations, variable A 2 and R 3Each of these is defined as one of the implementation schemes described in the combined IB above.

[0247] As defined above, Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R)1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 -C(O)-C(O)-OH, -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 or -N(R) 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl); or i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A replace; The condition is when B 1 Is it an R that appears 0 or 1 times? 2 Substituted 6-membered aryl ring or B 1 It is R that appears 0 times 2 Replacement When Z is not -C(O)R 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

[0248] In some implementations, Z is one of the following: a) -C(O)-(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A)-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -C(O)-N(R 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl); c) -C(O)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl) or -C(O)-C(O)-(C 1-6 hydroxyalkyl); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl); f) -N(R 1A)-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl) or -N(R) 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 Alkyl); or h) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A replace; The condition is when B 1 Is it an R that appears 0 or 1 times? 2 Substituted 6-membered aryl ring or B 1 It is R that appears 0 times 2 Replacement When Z is not -C(O)-(C 1-6 (hydroxyalkyl).

[0249] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); conditions are when B 1 Is it an R that appears 0 or 1 times? 2 Substituted 6-membered aryl ring or B 1 It is R that appears 0 times 2 Replacement When Z is not -C(O)R 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

[0250] In some implementations, Z is -C(O)-(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (Cycloalkyl). In some embodiments, Z is -C(O)-(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); conditions are when B 1 Is it an R that appears 0 or 1 times? 2 Substituted 6-membered aryl ring or B 1 It is R that appears 0 times 2 Replacement When Z is not -C(O)-(C 1-6 (hydroxyalkyl).

[0251] In some implementations, Z is -C(O)R 4 or -C(O)-(C 1-4 (alkylene)-R 4 In some implementations, Z is -C(O)R 4 or -C(O)-(C 1-4 (alkylene)-R 4 Condition B 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring or the presence of 0 R 2 Replacement .

[0252] In some implementations, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (cycloalkyl).

[0253] In some implementations, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (Cycloalkyl). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 alkyl) or -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 In some implementations, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 alkyl) or -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4Alkyl group). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (Cycloalkyl). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (cycloalkyl).

[0254] In some implementations, Z is -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 .

[0255] In some implementations, Z is -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl) or -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 (cycloalkyl).

[0256] In some implementations, Z is -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -C(O)-N(R 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl).

[0257] In some implementations, Z is -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 alkyl) or -C(O)-N(R 1A )-(C 1-4 (Haloalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 .

[0258] In some implementations, Z is -C(O)-C(O)-N(R) 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 -C(O)-C(O)-OH, -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R)1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace).

[0259] In some implementations, -C(O)-C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl) or -C(O)-C(O)-(C 1-6 (hydroxyalkyl).

[0260] In some implementations, Z is -C(O)-C(O)-N(R) 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl) or -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 Or -C(O)-C(O)-OH. In some embodiments, Z is -C(O)-C(O)-N(R) 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R)1A )-S(O)2-(C 1-6 Alkyl) or -C(O)-C(O)-N(R) 1A )-(C 1-4 Alkylene group (5-membered heteroaryl group containing 1-4 nitrogen atoms).

[0261] In some implementations, Z is -C(O)-C(O)-R 4 Or -C(O)-C(O)-OH. In some embodiments, Z is -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace).

[0262] In some implementations, Z is -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 Alkyl group). In some embodiments, Z is -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C)-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl).

[0263] In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl).

[0264] In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 (halogenated alkyl) or -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 In some implementations, Z is -N(R) 1A)-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl).

[0265] In some implementations, Z is -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 or -N(R) 1A )-S(O)2-R 7 In some implementations, Z is -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl) or -N(R) 1A )-S(O)2-R 7 In some implementations, Z is -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl) or -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 .

[0266] In some implementations, Z is -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C In some implementations, Z is -S(O)2-(C). 1-6 hydroxyalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-N(R) 1A )-(C 1-6 hydroxyalkyl) or -S(O)2-N(R 1A (R) 1B In some implementations, Z is -S(O)2-N(R). 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C In some implementations, Z is -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R)1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-[(C 1-4 [alkylene]-O-] x -(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 alkyl).

[0267] In some implementations, Z is -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl).

[0268] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 and -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 and -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 Hydroxyalkyl); conditions are when B 1 Is it an R that appears 0 or 1 times? 2 Substituted 6-membered aryl ring or B 1 It is R that appears 0 times 2 Replacement When Z is not -C(O)R 4 .

[0269] In some implementations, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl) or -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -C(O)R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl) or -N(R 1A )-C(O)-C(O)-N(R1B )-(C 1-6 Hydroxyalkyl); conditions are when B 1 Is it an R that appears 0 or 1 times? 2 Substituted 6-membered aryl ring or B 1 It is R that appears 0 times 2 Replacement When Z is not -C(O)R 4 .

[0270] In some implementations, Z is -C(O)R 4 In some implementations, Z is -C(O)R 4 The condition is B. 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring or the presence of 0 R 2 Replacement In some implementations, Z is -C(O)-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-(C 1-6 Hydroxyalkyl), under condition B 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring or the presence of 0 R 2 Replacement In some implementations, Z is -C(O)-(C 1-4 (alkylene)-R 4 In some implementations, Z is -C(O)-(C 1-4 (alkylene)-R 4 The condition is B. 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring or the presence of 0 R 2 Replacement .

[0271] In some implementations, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 In some implementations, Z is -C(O)-(C 1-4 alkylene)-N(R 1A)-C(O)-(R appearing z times) 9 Replacement C 3-8 (Cycloalkyl). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C replaced by a -OH group) 3-8 (Cycloalkyl). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 5-8 Bridged bicyclic cycloalkyl groups). In some embodiments, Z is -C(O)- (wherein each is separated by a C). 1-4 Alkyl and an -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl group. In some embodiments, Z is -C(O)- (substituted with a -N(R)-). 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (Cycloalkyl). In some embodiments, Z is -C(O)- (intercalated by a -N(R)-). 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) co-substituted C 3-7 (cycloalkyl).

[0272] In some implementations, Z is -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-(C replaced by one halogenated group) 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1A (R) 1B In some implementations, Z is -C(O)-N(R). 1A )-(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A )-(C 1-4 (Haloalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-(C 1-4alkylene)-O-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B In some implementations, Z is -C(O)-N(R). 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 In some implementations, Z is -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A )-(C 0-4 (alkylene)-(tetrahydrofuranyl or tetrahydropyranyl). In some embodiments, Z is -C(O)-N(R 1A )-(C 1-4 alkylene)-(C3-7 (Cycloalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-S(O)2-R 7 .

[0273] In some implementations, Z is -C(O)-C(O)-N(R) 1A )-R 5 In some implementations, Z is -C(O)-C(O)-N(R) 1A )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -C(O)-C(O)-N(R 1A (R) 1B In some implementations, Z is -C(O)-C(O)-N(R). 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-C(O)-N(R) 1A )-(C 1-4 Alkylene group (a 5-membered heteroaryl group containing 1-4 nitrogen atoms). In some embodiments, Z is -C(O)-C(O)-R 4 In some implementations, Z is -C(O)-C(O)-OH.

[0274] In some implementations, Z is -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B In some implementations, Z is -C(O)-O-(with one occurrence of -N(R)). 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 Hydroxyalkyl). In some embodiments, Z is -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace).

[0275] In some implementations, Z is -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6Hydroxyalkyl). In some embodiments, Z is -N(R 1A )-C(O)-C(O)-N(R 1B (R) 1C In some implementations, Z is -N(R). 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl).

[0276] In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 Hydroxyalkyl). In some embodiments, Z is -N(R 1A )-C(O)-N(R 1B )-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -N(R 1A )-C(O)-N(R 1B (R) 1C In some implementations, Z is -N(R). 1A )-C(O)-N(R 1B )-(C 1-4 (Haloalkyl). In some embodiments, Z is -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 (alkylene)-(tetrahydrofuranyl or tetrahydropyranyl). In some embodiments, Z is -N(R 1A Z is -C(O)-(morpholinyl). In some embodiments, Z is -N(R 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl).

[0277] In some implementations, Z is -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl group). In some embodiments, Z is -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 In some implementations, Z is -N(R) 1A )-S(O)2-R 7 In some implementations, Z is -N(R) 1A )-S(O)2-(C 0-4 alkylene)-N(R 1A (R) 1B In some implementations, Z is -N(R). 1A )-S(O)2-(C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl group). In some embodiments, Z is -N(R) 1A )-S(O)2-N(R 1B )-C(O)-OR 8 In some implementations, Z is -N(R) 1A )-S(O)2-N(R 1B )-CO2-(C 1-4 (alkylene)-(phenyl).

[0278] In some implementations, Z is -S(O)2-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -S(O)2-(C 1-4 alkylene)-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 In some implementations, Z is -S(O)2-[(C 1-4 [alkylene]-O-] x -(C1-6 Alkyl group). In some embodiments, Z is -S(O)2-N(R) 1A )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -S(O)2-N(R 1A (R) 1B In some implementations, Z is -S(O)2-N(R). 1A )-C(O)-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-N(R) 1A )-C(O)-N(R 1B (R) 1C ).

[0279] In some implementations, Z is -(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -(C 1-4 (alkylene)-C(O)-OH. In some embodiments, Z is -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl).

[0280] In some embodiments, Z is a 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replacement. In some implementations, Z is replaced by a C. 1-4 Alkyl-substituted oxazolidinone or imidazolidinone.

[0281] In some implementations, Z is , , , , , , , , , , , , , , , , , , , , , or In some implementations, Z is , , , , , , , , , , , , , , , , , , , , , or The condition is if B 1 Is it an R that appears 0 or 1 times? 2 The substituted 6-membered aryl ring or the presence of 0 R 2 Replacement Then Z is not .

[0282] In some implementations, Z is , , or The condition is if B 1 Is it an R that appears 0 or 1 times? 2 The substituted 6-membered aryl ring or the presence of 0 R 2 Replacement Then Z is not .

[0283] In some implementations, Z is , , , , or The condition is if B 1 Is it an R that appears 0 or 1 times? 2 The substituted 6-membered aryl ring or the presence of 0 R 2 Replacement Then Z is not In some implementations, Z is , or The condition is if B 1 Is it an R that appears 0 or 1 times? 2 The substituted 6-membered aryl ring or the presence of 0 R 2 Replacement Then Z is not In some implementations, Z is , , , or In some implementations, Z is or In some implementations, Z is , or .

[0284] In some implementations, Z is , , , , , , , , or In some implementations, Z is , , , or In some implementations, Z is , or In some implementations, Z is or .

[0285] In some implementations, Z is , , or The condition is if B 1 Is it an R that appears 0 or 1 times? 2 The substituted 6-membered aryl ring or the presence of 0 R 2 Replacement Then Z is not .

[0286] In some implementations, Z is In some implementations, Z is Condition B 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring or the presence of 0 R2 Replacement In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is Condition B 1 Not R that appears 0 or 1 2 The substituted 6-membered aryl ring or the presence of 0 R 2 Replacement In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is .

[0287] In some implementations, Z is , , , , , or In some implementations, Z is , , , , , , , , or In some implementations, Z is , , , , , , , , , , , or In some implementations, Z is , , , , , or In some implementations, Z is or .

[0288] As generally defined above, z is 1, 2, or 3. In some implementations, z is 1. In some implementations, z is 2. In some implementations, z is 3.

[0289] In some implementations, variable R 1A R 1B R 1C R 2 R 4 R 5 R 6 R 7 R 8 R 9 The definition of each of p and x is one of the implementation schemes described in the above-mentioned combination formula I.

[0290] The foregoing describes several embodiments of compounds relating to formula ID. This patent application specifically covers all combinations of the described embodiments.

[0291] Another aspect of the present invention provides a compound represented by formula I-1: (I-1) Or its pharmaceutically acceptable salt; wherein: A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 5-6-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur; A 2It is a 6-membered saturated or partially unsaturated heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5-8-membered saturated bicyclic carbocyclic group, or a covalent bond containing one heteroatom selected from nitrogen, wherein the heterocyclic group, monocyclic carbocyclic group, and bicyclic carbocyclic group are separated by 0 or 1 R atoms. 3 replace; R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 alkyl; R 2 Each occurrence independently represents halogenation; R 3 Is it halogenated or C 1-4 alkyl; Z is -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-N(R 1B (R) 1C ), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -N(R) 1A )-C(O)-(C 1-4 alkylene group (5-6 membered saturated heterocyclic group containing 1 oxygen atom), -N(R1A )-C(O)-O-(C 1-4 alkylene)-(phenyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -N(R 1A )-C(O)-N(R 1B )-[(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy group), -C(O)N(R 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy group, -C(O)-C(O)-OH, -C(O)-C(O)-N(R) 1A (R) 1B ), -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -C(O)-N(R) 1A )-S(O)2-R 7 -N(R) 1A )-S(O)2-R 7 -N(R)1A )-S(O)2-N(R 1B )-CO2-(C 1-4 alkylene)-phenyl, -C(O)-C(O)-N(R 1A )-S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy group), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl containing 1-4 nitrogen atoms), -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 (Substitution) or hydrogen; R 4 It is C 1-6 Hydroxyl group, 3-7 saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, 5-7 bis-oxo-heterocyclic group or 3-7 saturated carbocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups. R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy) or C 1-6 Alkoxy; R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl or C 1-4 Halogenated alkyl groups; R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ) or -N(R 1B )-C(O)-OR 8 ; R 8 It is C 1-4 Alkyl or -(C 0-4 alkylene)-(phenyl); R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C1-4 alkyl); m is 1 or 2; n is 1 or 2; p is 0, 1, 2, 3 or 4; x is 1, 2, 3, 4, or 5; and y and z are independently 1, 2, or 3; The condition is when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

[0292] The definition of the variable in Equation I-1 above covers multiple chemical groups. This application considers embodiments in which, for example (i) the variable is defined as a single chemical group selected from those chemical groups listed above, (ii) the variable is defined as a set of two or more chemical groups selected from those listed above, and (iii) the compound is defined by a combination of variables, wherein the variable is defined by (i) or (ii).

[0293] In some embodiments, the compound is a compound of formula I-1.

[0294] As generally defined above, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 5-6-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur. In some embodiments, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring. In some embodiments, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 5-6 membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur. In some embodiments, A 1 It is R that appears in p times. 2 Replacement B 1 It is a 5-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur. In some embodiments, A 1 It is R that appears in p times. 2 Replacement B 1It is a 6-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur.

[0295] In some implementations, A 1 yes , , or Each of these is replaced by p halogenated atoms. In some implementations, A 1 It was replaced by p instances of halogenated atoms. In some implementations, A 1 It was replaced by p instances of halogenated atoms. In some implementations, A 1 It was replaced by p instances of halogenated atoms. In some implementations, A 1 It was replaced by p instances of halogenated atoms. .

[0296] In some implementations, A 1 yes , , , , , , , , , , or In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A1 yes In some implementations, A 1 The groups are selected from those described in compounds I-1 to I-180 in Table 1 below.

[0297] As generally defined above, A 2 It is a 6-membered saturated or partially unsaturated heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5-8-membered saturated bicyclic carbocyclic group, or a covalent bond containing one heteroatom selected from nitrogen, wherein the heterocyclic group, monocyclic carbocyclic group, and bicyclic carbocyclic group are separated by 0 or 1 R atoms. 3 Replacement. In some implementations, A 2 Each of them is represented by 0 or 1 occurrences of R. 3 Replacement , , , , , Or a covalent bond, where *** is the connection point with Z. In some implementations, A 2 It is a 6-membered saturated or partially unsaturated heterocyclic group containing one heteroatom selected from nitrogen, wherein the heterocyclic group is separated by 0 or 1 R atoms. 3 Replacement. In some implementations, A 2 It is a 6-membered saturated or partially unsaturated monocyclic carbocyclic group, wherein the monocyclic carbocyclic group is represented by 0 or 1 R groups. 3 Replacement. In some implementations, A 2 It is a 5-8 nucleotide saturated bicyclic carbocyclic group, wherein the bicyclic carbocyclic group is represented by 0 or 1 R groups. 3 Replacement. In some implementations, A 2 It is a covalent bond. In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement , where *** is the connection point with Z. In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement , where *** is the connection point with Z. In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement , where *** is the connection point with Z. In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement , where *** is the connection point with Z. In some implementations, A 2 Is it an R that appears 0 or 1 times? 3Replacement , where *** is the connection point with Z. In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement , where *** is the connection point with Z. In some implementations, A 2 yes or Each of them is represented by 0 or 1 occurrences of R. 3 Replace, where *** is the connection point with Z. In some implementations, A 2 The groups are selected from those described in compounds I-1 to I-180 in Table 1 below.

[0298] As generally defined above, R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 Alkyl group. In some embodiments, R 1A It is hydrogen. In some implementations, R 1A It is C 1-4 Alkyl group. In some embodiments, R 1B It is hydrogen. In some implementations, R 1B It is C 1-4 Alkyl group. In some embodiments, R 1C It is hydrogen. In some implementations, R 1C It is C 1-4 Alkyl group. In some embodiments, R 1A and R 1B Both are hydrogen. In some implementations, R 1A and R 1B Both are methyl groups. In some embodiments, R 1A The groups are selected from those described in compounds I-1 to I-180 in Table 1 below.

[0299] As generally defined above, R 2 Each occurrence independently represents halogenation. In some implementations, R 2 It is either fluorinated or chlorinated. In some embodiments, R 2 It is fluorinated. In some implementations, R 2 It is chlorinated. In some implementations, R 2 The groups are selected from those described in compounds I-1 to I-180 in Table 1 below.

[0300] As generally defined above, R 3 Is it halogenated or C 1-4 Alkyl group. In some embodiments, R 3 It is halogenated. In some implementations, R3 It is C 1-4 Alkyl group. In some embodiments, R 3 It is fluorinated. In some implementations, R 3 It is chlorinated. In some implementations, R 3 It is methyl. In some embodiments, R 3 The groups are selected from those described in compounds I-1 to I-180 in Table 1 below.

[0301] As generally defined above, Z is -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-N(R 1B (R) 1C ), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -N(R) 1A )-C(O)-(C 1-4 alkylene group (5-6 membered saturated heterocyclic group containing 1 oxygen atom), -N(R 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-]x -R 6 -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -N(R 1A )-C(O)-N(R 1B )-[(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy group), -C(O)N(R 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy group, -C(O)-C(O)-OH, -C(O)-C(O)-N(R) 1A (R) 1B ), -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -C(O)-N(R) 1A )-S(O)2-R 7 -N(R) 1A )-S(O)2-R 7 -N(R) 1A )-S(O)2-N(R 1B )-CO2-(C 1-4 alkylene)-phenyl, -C(O)-C(O)-N(R 1A )-S(O)2-(C1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy group), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl containing 1-4 nitrogen atoms), -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 (Substitute) or hydrogen.

[0302] In some embodiments, Z is hydrogen. In some embodiments, Z is... , , , , or In some implementations, Z is , , , , , , , , , , , , , , , , , or In some implementations, Z is , , , , , , , , or In some implementations, Z is , , , , , , , , , , , , , , or In some implementations, Z is , , , , , , , , , , , or In some implementations, Z is , , , , , or In some implementations, Z is , , , , , , , or In some implementations, Z is or .

[0303] In some implementations, Z is... In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is .

[0304] In some implementations, Z is -C(O)R 4 In some implementations, Z is -C(O)-(C 1-4 (alkylene)-R 4 In some embodiments, Z is -C(O)-OH. In some embodiments, Z is -C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A (R) 1B In some implementations, Z is -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B In some implementations, Z is -C(O)-O-(with one occurrence of -N(R)). 1A (R) 1B ) replaced by C 1-4alkylene)-(C 1-4 Hydroxyalkyl). In some embodiments, Z is -S(O)2-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-(C 3-7 (Cycloalkyl). In some embodiments, Z is -S(O)2-N(R 1A (R) 1B In some implementations, Z is -S(O)2-N(R). 1A )-C(O)-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-N(R) 1A )-C(O)-N(R 1B (R) 1C In some implementations, Z is -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 In some implementations, Z is -N(R) 1A )-C(O)-(C 1-4 Alkylene group (5-6 membered saturated heterocyclic group containing one oxygen atom). In some embodiments, Z is -N(R 1A )-C(O)-O-(C 1-4 (alkylene)-(phenyl). In some embodiments, Z is -N(R 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 In some implementations, Z is -C(O)-N(R) 1A )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B In some implementations, Z is -N(R). 1A )-C(O)-N(R 1B )-[(C1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-C(O)-OH. In some embodiments, Z is -C(O)-C(O)-N(R) 1A (R) 1B In some implementations, Z is -N(R). 1A )-C(O)-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-C(O)-N(R) 1A )-R 5 In some implementations, Z is -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C In some implementations, Z is -C(O)-N(R). 1A )-S(O)2-R 7 In some implementations, Z is -N(R) 1A )-S(O)2-R 7 In some implementations, Z is -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy group), -C(O)-C(O)-N(R) 1A )-(C 1-4 Alkylene)-(a 5-membered heteroaryl group containing 1-4 nitrogen atoms). In some embodiments, Z is -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 (Replacement). In some implementations, Z is hydrogen.

[0305] In some implementations, Z is -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)N(R 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 Alkyl group). In some embodiments, Z is -N(R)1A )-S(O)2-N(R 1B )-CO2-(C 1-4 (alkylene)-phenyl.

[0306] In some embodiments, Z is selected from the groups depicted in compounds I-1 to I-180 in Table 1 below.

[0307] As generally defined above, R 4 It is C 1-6 Hydroxyl alkyl, a 3-7 membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, a 5-7 membered di-oxo-heterocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen, and oxygen, or a 3-7 membered saturated carbocyclic group, wherein the heterocyclic group and carbocyclic group are substituted with 0 or 1 hydroxyl groups. In some embodiments, R 4 It is C 1-6 Hydroxyl alkyl, a 3-7 membered saturated heterocyclic group or a 3-7 membered saturated carbocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by one or more hydroxyl groups. In some embodiments, R 4 It is C 1-6 Hydroxyalkyl. In some embodiments, R 4 It is a 3-7 membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 3-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 4-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 5-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 6-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or two hydroxyl groups. In some embodiments, R 4 It is a 7-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 3-7 member saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 3-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4It is a 4-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 5-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 6-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 7-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 5-7 membered di-oxo-heterocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen, and oxygen. In some embodiments, R 4 The groups are selected from those described in compounds I-1 to I-180 in Table 1 below.

[0308] As generally defined above, R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy) or C 1-6 Alkyl group. In some embodiments, R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl or C 1-6 Alkyl group. In some embodiments, R 5 It is C 1-6 Alkyl group. In some embodiments, R 5 It is C 1-6 Hydroxyalkyl. In some embodiments, R 5 It is C 1-6 Alkyl group. In some embodiments, R 5 Yes - (C 1-4 alkylene)-(C 1-4 Alkyl group). In some embodiments, R 5 The groups are selected from those described in compounds I-1 to I-180 in Table 1 below.

[0309] As generally defined above, R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl or C 1-4 Halogenated alkyl groups. In some embodiments, R 6 It is C 1-4 Alkyl group. In some embodiments, R 6 It is C 1-4 Hydroxyalkyl. In some embodiments, R 6 It is C 1-4 Halogenated alkyl groups. In some embodiments, R6 The groups are selected from those described in compounds I-1 to I-180 in Table 1 below.

[0310] As generally defined above, R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ) or -N(R 1B )-C(O)-OR 8 In some implementations, R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, -(C 0-4 alkylene)-N(R 1A (R) 1B ) or -N(R 1B )-C(O)-OR 8 In some implementations, R 7 It is C 1-4 Alkyl group. In some embodiments, R 7 It is C 1-4 Alkyl group. In some embodiments, R 7 Yes - (C 0-4 alkylene)-N(R 1A (R) 1B In some implementations, R 7 It is -N(R) 1B )-C(O)-OR 8 In some implementations, R 7 Yes - (C 1-4 alkylene)-(C 1-4 Alkyl group). In some embodiments, R 7 The groups are selected from those described in compounds I-1 to I-180 in Table 1 below.

[0311] As generally defined above, R 8 It is C 1-4 Alkyl or -(C 0-4 (alkylene)-(phenyl). In some embodiments, R 8 It is C 1-4 Alkyl group. In some embodiments, R 8 Yes - (C 0-4 (alkylene)-(phenyl). In some embodiments, R 8 The groups are selected from those described in compounds I-1 to I-180 in Table 1 below.

[0312] As generally defined above, R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C 1-4 Alkyl). In some embodiments, R 9 It is an oxidation process. In some implementations, R... 9 It is C 1-4 Alkyl group. In some embodiments, R 9 It is a hydroxyl group. In some embodiments, R 9 It is -C(O)-O-(C 1-4 Alkyl). In some embodiments, R 9 The groups are selected from those described in compounds I-1 to I-180 in Table 1 below.

[0313] As generally defined above, m is 1 or 2. In some implementations, m is 1. In some implementations, m is 2.

[0314] As generally defined above, n is 1 or 2. In some implementations, n is 1. In some implementations, n is 2.

[0315] As generally defined above, p is 0, 1, 2, 3, or 4. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is selected from the corresponding values ​​of the groups depicted in compounds I-1 to I-180 of Table 1 below.

[0316] As generally defined above, x is 1, 2, 3, 4, or 5. In some embodiments, x is 1. In some embodiments, x is 2. In some embodiments, x is 3. In some embodiments, x is 4. In some embodiments, x is 5. In some embodiments, x is selected from the corresponding values ​​of the groups depicted in compounds I-1 to I-180 in Table 1 below.

[0317] As generally defined above, y and z are independently 1, 2, or 3. In some embodiments, y is 1. In some embodiments, y is selected from the corresponding value of the groups depicted in the compounds in Table 1 below. In some embodiments, y is 2. In some embodiments, y is 3. In some embodiments, z is 1. In some embodiments, z is 2. In some embodiments, z is 3. In some embodiments, z is selected from the corresponding value of the groups depicted in compounds I-1 to I-180 in Table 1 below.

[0318] The foregoing describes several embodiments of compounds relating to formula I-1. This patent application specifically covers all combinations of the described embodiments.

[0319] In some embodiments, the compounds of formula I are further defined by formula Ia: (Ia) Or its pharmaceutically acceptable salt. In some embodiments, variable A 1 A 2 R 1 The definition of Z is one of the implementation schemes described above regarding Equation I. In some implementation schemes, variable A... 1 A 2 R 1 The definition of Z is one of the implementation schemes described above with respect to Equation I-1.

[0320] In some embodiments, the compounds of formula I are further defined by formula Ib: (Ib) Or its pharmaceutically acceptable salt, wherein: B 1 It is a 6-membered aryl ring or a 5-6-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur, wherein the aryl and heteroaryl groups are represented by p R atoms. 2 replace.

[0321] In some implementations, variable A 2 R 1 The definition of Z is one of the implementation schemes described above regarding Equation I. In some implementation schemes, variable A... 2 R 1 The definition of Z is one of the implementation schemes described above with respect to Equation I-1.

[0322] In some implementations, B 1 yes , , or Each of these is replaced by 0, 1, 2, 3, or 4 halogenated groups. In some embodiments, B 1 yes , , , , , , , , , , or .

[0323] The foregoing describes several embodiments of compounds of formula Ib. This patent application specifically covers all combinations of the described embodiments.

[0324] In some embodiments, the compounds of formula I are further defined by formula Ic: (Ic) Or its pharmaceutically acceptable salt, wherein: B 1 It is a 6-membered aryl ring or a 5-6-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur, wherein the aryl and heteroaryl groups are represented by p R atoms. 2 Replacement. In some implementations, variable A 2 R 1 The definition of Z is one of the implementation schemes described above regarding Equation I. In some implementation schemes, variable A... 2 R 1 The definition of Z is one of the implementation schemes described above with respect to Equation I-1. In some implementation schemes, B 1 yes , , or Each of these is replaced by 0, 1, 2, 3, or 4 halogenated groups. In some embodiments, B 1 yes , , , , , , , , , , or .

[0325] The foregoing describes several embodiments of compounds relating to formula Ic. This patent application specifically covers all combinations of the described embodiments.

[0326] In some embodiments, the compounds of formula I are further defined by formula Id: (Id) Or a pharmaceutically acceptable salt thereof, wherein X is -C(H)- or -N-. In some embodiments, X is -C(H)-. In some embodiments, X is -C(R)-. 2 )-, and the aromatic ring of isoindoline is surrounded by 0, 1, 2 or 3 additional R- 2 Replacement. In some implementations, X is -C(R) 2 )-, and the aromatic ring of isoindoline is not affected by any additional R. 2 Replacement. In some implementations, X is -C(R)2 )-, and the aromatic ring of isoindoline is separated by an additional R 2 Replacement. In some implementations, X is -C(R) 2 )-, and the aromatic ring of isoindoline is separated by two additional R- 2 Replacement. In some implementations, X is -N-. In some implementations, variable A 2 R 2 The definitions of , p, and Z are one of the implementation schemes described above with respect to Equation I. In some implementation schemes, variable A 2 R 2 The definitions of , p and Z are one of the implementation schemes described above with respect to Equation I-1.

[0327] In some embodiments, the compounds of formula I are further defined by formula Ie: (Ie) Or a pharmaceutically acceptable salt thereof, wherein Y and Q each independently represent N or S. In some embodiments, variable A 2 The definition of Z is one of the implementation schemes described above regarding Equation I. In some implementation schemes, variable A... 2 The definition of Z is one of the implementation schemes described above with respect to Equation I-1.

[0328] In some embodiments, the compounds of formula I are further defined by formulas If, Ig, Ih, or Ii: Or its pharmaceutically acceptable salt. In some embodiments, variable R 2 The definitions of , p, and Z are one of the implementation schemes described above with respect to Equation I. In some implementation schemes, the variable R... 2 The definitions of , p and Z are one of the implementation schemes described above with respect to Equation I-1.

[0329] In some embodiments, the compounds of formula I are further defined by formula Ij or Ik: Or its pharmaceutically acceptable salt. In some embodiments, variable R 2 The definitions of , p, and Z are one of the implementation schemes described above with respect to Equation I. In some implementation schemes, the variable R... 2 The definitions of , p and Z are one of the implementation schemes described above with respect to Equation I-1.

[0330] In some embodiments, the compounds of formula I are further defined by formula II: (Il) Or a pharmaceutically acceptable salt thereof. In some embodiments, the variable Z is defined as one of the embodiments described above with respect to Formula I. In some embodiments, the variable Z is defined as one of the embodiments described above with respect to Formula I-1.

[0331] The foregoing describes several embodiments of compounds of formula Il. This patent application specifically covers all combinations of the described embodiments.

[0332] Another aspect of the present invention provides compounds represented by formula IA: (IA) Or its pharmaceutically acceptable salt; wherein: A 1 yes , , or Each of them is replaced by p occurrences of halogenated halogens; A 2 It is a covalent bond; or A 2 yes , , , , or Each of them is represented by 0 or 1 occurrences of R. 3 Replace, where *** is the connection point with Z; R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 alkyl; R 3 Is it halogenated or C 1-4 alkyl; Z is -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C1-4 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-N(R 1B (R) 1C ), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -N(R) 1A )-C(O)-(C 1-4 alkylene group (5-6 membered saturated heterocyclic group containing 1 oxygen atom), -N(R 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -N(R 1A )-C(O)-N(R 1B )-[(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy group, -C(O)-C(O)-OH, -C(O)-C(O)-N(R) 1A (R) 1B ), -N(R1A )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -C(O)-N(R) 1A )-S(O)2-R 7 -N(R) 1A )-S(O)2-R 7 -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy group), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl containing 1-4 nitrogen atoms), -C(O)-O-(C 1-4 Alkylene group (a 5-membered saturated heterocyclic group containing one nitrogen atom and one oxygen atom) or hydrogen, wherein the heterocyclic group is represented by z R atoms. 9 replace); R 4 It is C 1-6 Hydroxyl alkyl, 3-7 membered saturated heterocyclic group or 3-7 membered saturated carbocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups; R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl or C 1-6 Alkoxy; R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl or C 1-4 Halogenated alkyl groups; R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, -(C 0-4 alkylene)-N(R 1A (R) 1B ) or -N(R 1B )-C(O)-OR 8 ; R 8 It is C 1-4 Alkyl or -(C 0-4 alkylene)-(phenyl); R9 It is oxygen, C 1-4 Alkyl or -C(O)-O-(C 1-4 alkyl); p is 0, 1, 2, 3 or 4; x is 1, 2, 3, 4, or 5; and y and z are 1, 2 or 3 independently.

[0333] In the above formula IA, the definition of the variable covers multiple chemical groups. This application contemplates embodiments in which, for example (i) the variable is defined as a single chemical group selected from those chemical groups listed above, (ii) the variable is defined as a collection of two or more chemical groups selected from those listed above, and (iii) the compound is defined by a combination of variables, wherein the variable is defined by (i) or (ii).

[0334] In some embodiments, the compound is a compound of formula IA.

[0335] As generally defined above, A 1 yes , , or Each of these is replaced by p halogenated atoms. In some implementations, A 1 It was replaced by p instances of halogenated atoms. In some implementations, A 1 It was replaced by p instances of halogenated atoms. In some implementations, A 1 It was replaced by p instances of halogenated atoms. In some implementations, A 1 It was replaced by p instances of halogenated atoms. In some implementations, A 1 yes , , , , , , , , , , or In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 yes In some implementations, A 1 Selected from the groups depicted in the compounds in Table 1 below.

[0336] As generally defined above, A 2 It is a covalent bond; or A 2 yes , , , , or Each of them is represented by 0 or 1 occurrences of R. 3 Replace, where *** is the connection point with Z. In some implementations, A 2 It is a covalent bond. In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement , where *** is the connection point with Z. In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement , where *** is the connection point with Z. In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement , where *** is the connection point with Z. In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement , where *** is the connection point with Z. In some implementations, A 2 Is it an R that appears 0 or 1 times? 3 Replacement , where *** is the connection point with Z. In some implementations, A 2 Is it an R that appears 0 or 1 times?3 Replacement , where *** is the connection point with Z. In some implementations, A 2 yes or Each of them is represented by 0 or 1 occurrences of R. 3 Replace, where *** is the connection point with Z. In some implementations, A 2 Selected from the groups depicted in the compounds in Table 1 below.

[0337] As generally defined above, R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 Alkyl group. In some embodiments, R 1A It is hydrogen. In some implementations, R 1A It is C 1-4 Alkyl group. In some embodiments, R 1B It is hydrogen. In some implementations, R 1B It is C 1-4 Alkyl group. In some embodiments, R 1C It is hydrogen. In some implementations, R 1C It is C 1-4 Alkyl group. In some embodiments, R 1A and R 1B Both are hydrogen. In some implementations, R 1A and R 1B Both are methyl groups. In some embodiments, R 1A Selected from the groups depicted in the compounds in Table 1 below.

[0338] As generally defined above, R 3 Is it halogenated or C 1-4 Alkyl group. In some embodiments, R 3 It is halogenated. In some implementations, R 3 It is C 1-4 Alkyl group. In some embodiments, R 3 It is fluorinated. In some implementations, R 3 It is chlorinated. In some implementations, R 3 It is methyl. In some embodiments, R 3 Selected from the groups depicted in the compounds in Table 1 below.

[0339] As generally defined above, Z is -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-OH, -C(O)-O-(C 1-6Alkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-N(R 1B (R) 1C ), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -N(R) 1A )-C(O)-(C 1-4 alkylene group (5-6 membered saturated heterocyclic group containing 1 oxygen atom), -N(R 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -N(R 1A)-C(O)-N(R 1B )-[(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy group, -C(O)-C(O)-OH, -C(O)-C(O)-N(R) 1A (R) 1B ), -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -C(O)-N(R) 1A )-S(O)2-R 7 -N(R) 1A )-S(O)2-R 7 -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy group), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl containing 1-4 nitrogen atoms), -C(O)-O-(C 1-4 Alkylene group (a 5-membered saturated heterocyclic group containing one nitrogen atom and one oxygen atom) or hydrogen, wherein the heterocyclic group is represented by z R atoms. 9 Substitution. In some embodiments, Z is hydrogen. In some embodiments, Z is , , , , or In some implementations, Z is , , , , , , , , , , , , , , , , , or In some implementations, Z is , , , , , , , , or In some implementations, Z is , , , , , , , , , , , , , , or In some implementations, Z is , , , , , , , , , , , or In some implementations, Z is , , , , , or In some implementations, Z is , , , , , , , or In some implementations, Z is or .

[0340] In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is In some implementations, Z is .

[0341] In some implementations, Z is -C(O)R 4 In some implementations, Z is -C(O)-(C 1-4 (alkylene)-R 4 In some embodiments, Z is -C(O)-OH. In some embodiments, Z is -C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-N(R) 1A (R) 1B In some implementations, Z is -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B In some implementations, Z is -C(O)-O-(with one occurrence of -N(R)). 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 Hydroxyalkyl). In some embodiments, Z is -S(O)2-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-(C 3-7 (Cycloalkyl). In some embodiments, Z is -S(O)2-N(R 1A (R) 1B In some implementations, Z is -S(O)2-N(R). 1A )-C(O)-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl group). In some embodiments, Z is -S(O)2-N(R) 1A )-C(O)-N(R 1B (R) 1C In some implementations, Z is -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 In some implementations, Z is -N(R) 1A )-C(O)-(C 1-4 Alkylene group (5-6 membered saturated heterocyclic group containing one oxygen atom). In some embodiments, Z is -N(R 1A )-C(O)-O-(C 1-4(alkylene)-(phenyl). In some embodiments, Z is -N(R 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 In some implementations, Z is -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 In some implementations, Z is -C(O)-N(R) 1A )-(C 1-6 (Hydroxyalkyl). In some embodiments, Z is -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B In some implementations, Z is -N(R). 1A )-C(O)-N(R 1B )-[(C 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 Alkyl group). In some embodiments, Z is -C(O)-C(O)-OH. In some embodiments, Z is -C(O)-C(O)-N(R) 1A (R) 1B In some implementations, Z is -N(R). 1A )-C(O)-(C 1-6 Hydroxyalkyl). In some embodiments, Z is -C(O)-C(O)-N(R) 1A )-R 5 In some implementations, Z is -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C In some implementations, Z is -C(O)-N(R). 1A )-S(O)2-R 7 In some implementations, Z is -N(R) 1A )-S(O)2-R 7 In some implementations, Z is -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy group), -C(O)-C(O)-N(R) 1A )-(C 1-4 Alkylene)-(a 5-membered heteroaryl group containing 1-4 nitrogen atoms). In some embodiments, Z is -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 (Substitution). In some embodiments, Z is hydrogen. In some embodiments, Z is selected from the groups depicted in the compounds in Table 1 below.

[0342] As generally defined above, R 4 It is C 1-6 Hydroxyl alkyl, a 3-7 membered saturated heterocyclic group or a 3-7 membered saturated carbocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by one or more hydroxyl groups. In some embodiments, R 4 It is C 1-6 Hydroxyalkyl. In some embodiments, R 4 It is a 3-7 membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 3-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 4-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 5-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 6-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or two hydroxyl groups. In some embodiments, R 4 It is a 7-membered saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, wherein the heterocyclic group is substituted by one or more hydroxyl groups. In some embodiments, R 4 It is a 3-7 member saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 3-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4It is a 4-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 5-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 6-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 It is a 7-membered saturated carbocyclic group, wherein the carbocyclic group is substituted by 0 or 1 hydroxyl groups. In some embodiments, R 4 Selected from the groups depicted in the compounds in Table 1 below.

[0343] As generally defined above, R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl or C 1-6 Alkyl group. In some embodiments, R 5 It is C 1-6 Alkyl group. In some embodiments, R 5 It is C 1-6 Hydroxyalkyl. In some embodiments, R 5 It is C 1-6 Alkyl group. In some embodiments, R 5 Selected from the groups depicted in the compounds in Table 1 below.

[0344] As generally defined above, R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl or C 1-4 Halogenated alkyl groups. In some embodiments, R 6 It is C 1-4 Alkyl group. In some embodiments, R 6 It is C 1-4 Hydroxyalkyl. In some embodiments, R 6 It is C 1-4 Halogenated alkyl groups. In some embodiments, R 6 Selected from the groups depicted in the compounds in Table 1 below.

[0345] As generally defined above, R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, -(C 0-4 alkylene)-N(R 1A (R) 1B ) or -N(R 1B )-C(O)-OR 8 In some implementations, R 7 It is C 1-4 Alkyl group. In some embodiments, R7 It is C 1-4 Alkyl group. In some embodiments, R 7 Yes - (C 0-4 alkylene)-N(R 1A (R) 1B In some implementations, R 7 It is -N(R) 1B )-C(O)-OR 8 In some implementations, R 7 Selected from the groups depicted in the compounds in Table 1 below.

[0346] As generally defined above, R 8 It is C 1-4 Alkyl or -(C 0-4 (alkylene)-(phenyl). In some embodiments, R 8 It is C 1-4 Alkyl group. In some embodiments, R 8 Yes - (C 0-4 (alkylene)-(phenyl). In some embodiments, R 8 Selected from the groups depicted in the compounds in Table 1 below.

[0347] As generally defined above, R 9 It is oxygen, C 1-4 Alkyl or -C(O)-O-(C 1-4 Alkyl). In some embodiments, R 9 It is an oxidation process. In some implementations, R... 9 It is C 1-4 Alkyl group. In some embodiments, R 9 It is -C(O)-O-(C 1-4 Alkyl). In some embodiments, R 9 Selected from the groups depicted in the compounds in Table 1 below.

[0348] As generally defined above, p is 0, 1, 2, 3, or 4. In some embodiments, p is 1. In some embodiments, p is 2. In some embodiments, p is 3. In some embodiments, p is 4. In some embodiments, p is selected from the corresponding values ​​of the groups depicted in the compounds in Table 1 below.

[0349] As generally defined above, x is 1, 2, 3, 4, or 5. In some embodiments, x is 1. In some embodiments, x is 2. In some embodiments, x is 3. In some embodiments, x is 4. In some embodiments, x is 5. In some embodiments, x is selected from the corresponding values ​​of the groups depicted in the compounds in Table 1 below.

[0350] As generally defined above, y and z are independently 1, 2, or 3. In some embodiments, y is 1. In some embodiments, y is 2. In some embodiments, y is 3. In some embodiments, y is selected from the corresponding values ​​of the groups depicted in the compounds in Table 1 below. In some embodiments, z is 1. In some embodiments, z is 2. In some embodiments, z is 3. In some embodiments, z is selected from the corresponding values ​​of the groups depicted in the compounds in Table 1 below.

[0351] The foregoing describes several embodiments of compounds relating to formula IA. This patent application specifically covers all combinations of the described embodiments.

[0352] In the above formula IA, the definition of the variable covers multiple chemical groups. This application contemplates embodiments in which, for example, i) the variable is defined as a single chemical group selected from those chemical groups listed above, ii) the variable is defined as a collection of two or more chemical groups selected from those chemical groups listed above, and iii) the compound is defined by a combination of variables, wherein the variable is defined by (i) or (ii).

[0353] Exemplary specific compounds In some embodiments, the compound is a compound in Table 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound in Table 1. In some embodiments, the compound is a compound selected from I-1 to I-180 in Table 1 or a pharmaceutically acceptable salt thereof. In some embodiments, the compound is a compound selected from I-1 to I-180 in Table 1.

[0354] Table 1. Exemplary Compounds

[0355] In some embodiments, the compound is a compound in Table 1 or a pharmaceutically acceptable salt thereof, wherein at least one activity of the compound in one of the biochemical assays in Table 3 is "A" or "B". In some embodiments, the compound is a compound in Table 1 or a pharmaceutically acceptable salt thereof, wherein at least one activity of the compound in one of the biochemical assays in Table 3 is "A". In some embodiments, the compound is a compound in Table 1 or a pharmaceutically acceptable salt thereof, wherein at least one activity of the compound in one of the cell-based assays in Table 3 is "A" or "B". In some embodiments, the compound is a compound in Table 1 or a pharmaceutically acceptable salt thereof, wherein at least one activity of the compound in one of the cell-based assays in Table 3 is "A".

[0356] In some embodiments, the compound is a compound in Table 1, wherein at least one activity of the compound in one of the biochemical assays in Table 3 is "A" or "B". In some embodiments, the compound is a compound in Table 1, wherein at least one activity of the compound in one of the biochemical assays in Table 3 is "A". In some embodiments, the compound is a compound in Table 1, wherein at least one activity of the compound in one of the cell-based assays in Table 3 is "A". In some embodiments, the compound is a compound in Table 1, wherein at least one activity of the compound in one of the cell-based assays in Table 3 is "A".

[0357] In some embodiments, the compound is a compound in Table 1 or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula IB. In some embodiments, the compound is a compound in Table 1, wherein the compound is a compound of formula IB. In some embodiments, the compound is a compound in Table 1 or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula IC. In some embodiments, the compound is a compound in Table 1, wherein the compound is a compound of formula IC. In some embodiments, the compound is a compound in Table 1 or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula ID. In some embodiments, the compound is a compound in Table 1, wherein the compound is a compound of formula ID.

[0358] In some embodiments, the compound is one of the compounds in the table below or a pharmaceutically acceptable salt thereof: .

[0359] In some embodiments, the compound is a compound listed in the table above. In some embodiments, the compound is a compound listed in the table above or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula IB. In some embodiments, the compound is a compound listed in the table above, wherein the compound is a compound of formula IB. In some embodiments, the compound is a compound listed in the table above or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula IC. In some embodiments, the compound is a compound listed in the table above, wherein the compound is a compound of formula IC. In some embodiments, the compound is a compound listed in the table above or a pharmaceutically acceptable salt thereof, wherein the compound is a compound of formula ID. In some embodiments, the compound is a compound listed in the table above, wherein the compound is a compound of formula ID.

[0360] In some embodiments, the compound is one of the following: , , , , , , , , or .

[0361] Synthesis method The following synthetic schemes illustrate methods for preparing the compounds described herein. These schemes are given for illustrative purposes and are not intended to limit the scope or nature of the invention. The starting materials shown in the schemes are commercially available or can be prepared based on procedures described in the literature.

[0362] Scheme 1 illustrates a general method for preparing heteroaryl compound F. Amine A is coupled with a protected piperidine or other suitable reagent (e.g., cyclohexane, bicyclo[2.2.2]octane, dihydropyridine, etc.) using, for example, Suzuki or Stille coupling, to obtain compound B. Compound B is reacted with an acyl chloride to form urethane C. Uracarbamate C is then reacted with an optionally substituted isoindoline or other heteroaryl compound (e.g., pyrrolo-pyridine, pyrrolo-pyrazine, pyrrolo-thiazole, etc.) to form a protected isoindoline compound D. Compound D is deprotected to give a free amine compound E, which is then reacted with a carboxylic acid to form heteroaryl compound F. The Z group present in formulas I, I-1, IA, IB, IC, or ID above, and A... 2 Depending on the type of ring, other conventional methods can be used to replace the amine-carboxylic acid coupling step to convert compound E into heteroaryl F.

[0363] Option 1. In this scheme, those skilled in the art of organic synthesis will understand that the functional groups present on the various parts of the molecule should be compatible with the proposed reagents and reactions. Substituents incompatible with the reaction conditions will be readily apparent to those skilled in the art, and therefore alternative methods (e.g., using protecting groups or alternative reactions) will be indicated. Protecting group chemistry and strategies are well known in the art, for example, as described in detail in “Protecting Groups in Organic Synthesis,” TW Greene and PGM Wuts, 3rd edition, John Wiley & Sons, 1999, the entire contents of which are hereby incorporated by reference. Those skilled in the art can also readily modify the modular synthetic route shown in Scheme 1 by functional group transformations of the intermediates and the final compound to obtain other compounds. Such functional group transformations are well known in the art, for example, as described in “Comprehensive Organic Synthesis” (edited by BM Trost and I. Fleming, 1991–1992).

[0364] II. Therapeutic Applications The heteroaryl compounds described herein, such as compounds of formula I, I-1, IA, IB, IC, or ID, or other compounds in Part I, provide therapeutic benefits to subjects suffering from NAMPT-mediated diseases or symptoms. A description of exemplary therapeutic applications is provided below.

[0365] One aspect of the present invention provides a method for treating a disease or condition mediated by NAMPT. The method comprises administering a therapeutically effective amount of a compound described herein, such as a compound of formula I, I-1, IA, IB, IC, or ID, to a subject in need to treat the disease or condition.

[0366] Another aspect of the invention provides a method for treating the diseases or symptoms described herein. The method comprises administering a therapeutically effective amount of a compound described herein, such as a compound of formula I, I-1, IA, IB, IC, or ID, to a subject in need to treat the disease or symptom.

[0367] Another aspect of the present invention provides a method for inhibiting the activity of NAMPT. The method comprises contacting NAMPT with an effective amount of a compound described herein (such as a compound of formula I, I-1, IA, IB, IC, or ID) to inhibit the activity of the NAMPT.

[0368] In some embodiments, the disease or symptom is selected from proliferative disorders (e.g., cancer, tumor formation), inflammatory disorders (e.g., chronic inflammatory disorders, acute inflammatory disorders, autoinflammatory disorders), autoimmune disorders, fibrotic disorders, metabolic disorders, cardiovascular disorders, cerebrovascular disorders, and excessive inflammatory responses driven by myeloid cells in COVID-19 infection.

[0369] In some embodiments, the NAMPT-mediated disease or condition is NAMPT-negative cancer. In some embodiments, the NAMPT-mediated disease or condition is psoriasis, dermatitis, vitiligo, ichthyosis, alopecia areata, epidermolysis bullosa, hidradenitis suppurativa, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, or kidney disease. In some embodiments, the NAMPT-mediated disease or condition is inflammatory bowel disease.

[0370] In some embodiments, the heteroaryl compounds described herein, such as compounds of formula I, I-1, IA, IB, IC, or ID, or other compounds in Part I, provide therapeutic benefits to subjects suffering from cancer (e.g., pancreatic cancer, melanoma, glioma, lung cancer, colon cancer, rectal cancer, breast cancer, cervical cancer, prostate cancer, gastric cancer, skin cancer, liver cancer, bile duct cancer, nervous system cancer, lymphoma, leukemia), intestinal diseases or inflammatory bowel disease, hyperactive T-cell diseases, psoriasis, neurodegenerative diseases, acute kidney disease, inflammation, stroke, acute infarction, inflammatory bowel disease, acute lung injury, rheumatoid arthritis, nephropathy, fibrosis, or sepsis.

[0371] Another aspect of the invention provides the use of the compounds described herein (such as compounds of formula I, I-1, IA, IB, IC, or ID, or other compounds in Part I) in the preparation of a medicament. In some embodiments, the medicament is used to treat the diseases or conditions described herein, such as proliferative disorders, inflammatory disorders, or metabolic disorders.

[0372] Another aspect of the invention provides the use of the compounds described herein (such as compounds of formula I, I-1, IA, IB, IC or ID, or other compounds in Part I) for the treatment of diseases or conditions (such as those described herein).

[0373] In some implementations, the subject is a person. In some implementations, the subject is an adult. In some implementations, the subject is a child. In some implementations, the subject is an elderly person.

[0374] Exemplary diseases or symptoms Exemplary diseases and conditions include, but are not limited to, those described herein. In some embodiments, the disease or condition is a proliferative condition (e.g., cancer, tumor formation), an inflammatory condition (e.g., chronic inflammatory condition, acute inflammatory condition, autoinflammatory condition), an autoimmune condition, a fibrotic condition, a metabolic condition, a cardiovascular condition, a cerebrovascular condition, or an excessive inflammatory response driven by myeloid cells in COVID-19 infection. In some embodiments, the proliferative disease is cancer. In some embodiments, the proliferative disease is pancreatic cancer, melanoma, glioma, lung cancer, colon cancer, rectal cancer, breast cancer, cervical cancer, prostate cancer, gastric cancer, skin cancer, liver cancer, bile duct cancer, nervous system cancer, lymphoma, leukemia, or a combination thereof. In some embodiments, the disease or condition is an inflammatory condition (e.g., intestinal disease or inflammatory bowel disease, hyperactive T-cell disease, psoriasis, neurodegenerative disease, acute kidney disease, inflammation, stroke, acute infarction, inflammatory bowel disease, acute lung injury, rheumatoid arthritis, nephropathy, fibrosis, or sepsis). In some embodiments, the disease or symptom is NAPRT-negative cancer. In some embodiments, the disease or symptom is psoriasis, dermatitis, vitiligo, ichthyosis, alopecia areata, epidermolysis bullosa, hidradenitis suppurativa, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, or kidney disease. In some embodiments, the disease or symptom is inflammatory bowel disease.

[0375] Exemplary proliferative diseases include, but are not limited to, those described herein. In some embodiments, the proliferative disease or symptom to be treated or prevented using the compounds described herein is cancer.

[0376] Other exemplary cancers include, but are not limited to, acoustic neuroma; adenocarcinoma; adrenal carcinoma; anal cancer; angiosarcoma (e.g., lymphangiosarcoma, lymphangioendothelial sarcoma, angiosarcoma); appendix cancer; benign monoclonal immunoglobulinosis; biliary tract cancer (e.g., bile duct cancer); bladder cancer; breast cancer (e.g., adenocarcinoma of the breast, papillary carcinoma of the breast, breast cancer, medullary carcinoma of the breast, triple-negative breast cancer (TNBC)); brain cancer (e.g., meningioma, glioblastoma, glioma (e.g., astrocytoma)). Oligodendroglioma; medulloblastoma; bronchial carcinoma; carcinoid tumor; cervical cancer (e.g., cervical adenocarcinoma); chordoma; craniopharyngioma; colorectal cancer (e.g., colon cancer, rectal cancer, colorectal adenocarcinoma); connective tissue carcinoma; epithelial carcinoma; ependymoma; endothelial sarcoma (e.g., Kaposi's sarcoma, multiple idiopathic hemorrhagic sarcoma); endometrial cancer (e.g., uterine cancer, uterine sarcoma); esophageal cancer (e.g., esophageal adenocarcinoma, Barrett's adenocarcinoma); Ewing's sarcoma; ocular cancer (e.g. Intraocular melanoma, retinoblastoma; familial eosinophilia; gallbladder cancer; gastric cancer (e.g., gastric adenocarcinoma); gastrointestinal stromal tumor (GIST); germ cell cancer; head and neck cancer (e.g., head and neck squamous cell carcinoma, oral cancer (e.g., oral squamous cell carcinoma), pharyngeal cancer (e.g., laryngeal cancer, pharyngeal cancer, nasopharyngeal cancer, oropharyngeal cancer)); heavy chain disease (e.g., alpha chain disease, gamma chain disease, μ chain disease); hemangioblastoma; hypopharyngeal cancer; inflammatory myofibroblastic tumor; immune cell amyloidosis. Degeneration; renal cell carcinoma (e.g., nephroblastoma (also known as Wilms' tumor), renal cell carcinoma); liver cancer (e.g., hepatocellular carcinoma (HCC), malignant hepatocellular carcinoma); lung cancer (e.g., bronchogenic carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), lung adenocarcinoma); leiomyosarcoma (LMS); mastocytosis (e.g., systemic mastocytosis); muscle cancer; myelodysplastic syndrome (MDS); mesothelioma; myeloproliferative disorder (MPD) (e.g., polycythemia vera (PV), essential thrombocythemia (ET), unexplained myeloid metaplasia (AMM, also known as myelofibrosis (MF)), chronic idiopathic myelofibrosis, chronic myeloid leukemia (CML), chronic neutrophilic leukemia (CNL), eosinophilic syndrome (HES)); neuroblastoma; neurofibroma (e.g., neurofibromatosis type 1 or 2 (NF), Schwann cell carcinoma); neuroendocrine carcinoma (e.g., gastrointestinal pancreatic neuroendocrine tumor (GEP-NET), carcinoid tumor); osteosarcoma (e.g., bone cancer); ovarian cancer (e.g., cystadenocarcinoma, ovarian embryonal carcinoma, ovarian adenocarcinoma); papillary adenocarcinoma; pancreatic cancer (e.g., pancreatic adenocarcinoma, intraductal papillary mucinous tumor (IPMN), islet cell tumor); penile cancer (e.g., Paget's disease of the penis and scrotum); pineal tumor; primitive neuroectodermal tumor (PNT); plasmacytoma; paraneoplastic syndromes;Intraepithelial neoplasia; prostate cancer (e.g., prostate adenocarcinoma); rectal cancer; rhabdomyosarcoma; salivary gland cancer; skin cancer (e.g., squamous cell carcinoma (SCC), keratoacanthoma (KA), melanoma, basal cell carcinoma (BCC)); small bowel cancer (e.g., appendix cancer); soft tissue sarcoma (e.g., malignant fibrous histiocytoma (MFH), liposarcoma, malignant peripheral nerve sheath tumor (MPNST), chondrosarcoma, fibrosarcoma, myxosarcoma); sebaceous gland cancer; small bowel cancer; sweat gland cancer; synovial tumor; testicular cancer (e.g., seminoma, embryonal testicular carcinoma); thyroid cancer (e.g., papillary thyroid carcinoma (PTC), medullary thyroid carcinoma); urethral cancer; vaginal cancer; vulvar cancer (e.g., vulvar Paget's disease); Burkitt lymphoma; primary intraocular lymphoma; classical Hodgkin's lymphoma; biphenotypic acute leukemia; T-cell lymphoma; nasal T-cell lymphoma; enteropathy-type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma; blastic NK-cell lymphoma; T-cell prolymphocytic leukemia and NK-cell leukemia.

[0377] In some embodiments, the cancer is a hematologic malignancy. Exemplary hematologic malignancies include, but are not limited to, leukemias such as acute lymphoblastic leukemia (ALL) (e.g., B-cell ALL, T-cell ALL), acute myeloid leukemia (AML) (e.g., B-cell AML, T-cell AML), chronic myeloid leukemia (CML) (e.g., B-cell CML, T-cell CML), chronic lymphocytic leukemia (CLL) (e.g., B-cell CLL, T-cell CLL), acute non-lymphocytic leukemia (ANLL), acute promyelocytic leukemia (APL), and acute myelomonocytic leukemia (AMMoL); lymphomas such as Hodgkin lymphoma (HL) (e.g., B-cell HL, T-cell HL) and non-Hodgkin lymphoma (NHL) (e.g., B-cell NHL), such as diffuse large cell lymphoma (DLCL) (e.g., diffuse large B-cell lymphoma (DLBCL, e.g., activated B-cell (ABC) DLBCL). (ABC-DLBCL), follicular lymphoma, chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL), mantle cell lymphoma (MCL), marginal zone B-cell lymphoma (e.g., mucosa-associated lymphoid tissue (MALT) lymphoma, nodal marginal zone B-cell lymphoma, splenic marginal zone B-cell lymphoma), primary mediastinal B-cell lymphoma, Burkitt lymphoma, Waldenström macroglobulinemia (WM, lymphoplasmacytic lymphoma), hairy cell leukemia (HCL), immunoblastic large cell lymphoma, precursor B-cell lymphoblastic lymphoma, central nervous system (CNS) lymphoma (e.g., primary CNS lymphoma and secondary CNS lymphoma); and T-cell NHL, such as precursor T-cell lymphoblastic lymphoma / leukemia, peripheral T-cell lymphoma (PTCL) (e.g., cutaneous T-cell lymphoma (CTCL)). (e.g., mycosis fungoides, Cezari syndrome); angioimmunoblastic T-cell lymphoma, extranodal natural killer T-cell lymphoma, enteropathy-type T-cell lymphoma, subcutaneous panniculitis-like T-cell lymphoma, and anaplastic large cell lymphoma); immune-exempt site lymphomas (e.g., brain lymphoma, ocular lymphoma, placental lymphoma, fetal lymphoma, testicular lymphoma); mixed types of one or more of the above-described leukemias / lymphomas; myelodysplastic syndromes; multiple myeloma (MM); heavy chain diseases (e.g., alpha chain disease, gamma chain disease, μ chain disease), polycythemia vera, Wilms' tumor, and Ewing's sarcoma.

[0378] In some embodiments, the disease or condition is cancer. In some embodiments, the disease or condition is angiogenesis. In some embodiments, the disease or condition is multiple myeloma. In some embodiments, the disease or condition is leukemia (e.g., acute lymphoblastic leukemia, acute and chronic myeloid leukemia, chronic lymphocytic leukemia, acute lymphoblastic leukemia, chronic myelomonocytic leukemia, or promyelocytic leukemia).

[0379] In some embodiments, the cancer is a solid tumor, leukemia, or lymphoma. In some embodiments, the cancer is ovarian cancer, uterine cancer, endometrial cancer, cervical cancer, prostate cancer, testicular cancer, breast cancer, brain cancer, lung cancer, oral cancer, esophageal cancer, head and neck cancer, stomach cancer, colon cancer, rectal cancer, skin cancer, sebaceous gland cancer, bile duct and gallbladder cancer, liver cancer, pancreatic cancer, bladder cancer, urethral cancer, kidney cancer, eye cancer, or thyroid cancer.

[0380] In some embodiments, the disease or symptom is lymphoma (e.g., B-cell lymphoma, T-cell lymphoma, mantle cell lymphoma, diffuse large B-cell lymphoma, pilocytic lymphoma, Burkitt lymphoma, mast cell tumor, Hodgkin's disease, or non-Hodgkin's disease). In some embodiments, the disease or symptom is myelodysplastic syndrome. In some embodiments, the disease or symptom is fibrosarcoma. In some embodiments, the disease or symptom is rhabdomyosarcoma. In some embodiments, the disease or symptom is astrocytoma. In some embodiments, the disease or symptom is neuroblastoma. In some embodiments, the disease or symptom is glioma and schwannoma. In some embodiments, the disease or symptom is melanoma. In some embodiments, the disease or symptom is seminoma. In some embodiments, the disease or symptom is teratoma. In some embodiments, the disease or symptom is osteosarcoma. In some embodiments, the disease or symptom is xeroderma pigmentosum. In some embodiments, the disease or symptom is keratotic acanthoma. In some embodiments, the disease or symptom is follicular thyroid carcinoma. In some embodiments, the disease or symptom is Kaposi's sarcoma. In some embodiments, the disease or symptom is melanoma. In some embodiments, the disease or symptom is teratoma. In some embodiments, the disease or symptom is rhabdomyosarcoma. In some embodiments, the disease or symptom is metastatic and bone disease. In some embodiments, the disease or symptom is bone cancer. In some embodiments, the disease or symptom is oropharyngeal cancer. In some embodiments, the disease or symptom is esophageal cancer. In some embodiments, the disease or symptom is laryngeal cancer. In some embodiments, the disease or symptom is stomach cancer. In some embodiments, the disease or symptom is intestinal cancer. In some embodiments, the disease or symptom is colon cancer. In some embodiments, the disease or symptom is rectal cancer. In some embodiments, the disease or symptom is lung cancer (e.g., non-small cell lung cancer or small cell lung cancer). In some embodiments, the disease or symptom is liver cancer. In some embodiments, the disease or symptom is pancreatic cancer. In some embodiments, the disease or symptom is neurogenic cancer. In some embodiments, the disease or symptom is brain cancer (e.g., glioma or glioblastoma multiforme). In some embodiments, the disease or symptom is head and neck cancer. In some embodiments, the disease or symptom is pharyngeal cancer. In some embodiments, the disease or symptom is ovarian cancer. In some embodiments, the disease or symptom is uterine cancer. In some embodiments, the disease or symptom is prostate cancer. In some embodiments, the disease or symptom is testicular cancer. In some embodiments, the disease or symptom is bladder cancer. In some embodiments, the disease or symptom is kidney cancer.In some embodiments, the disease or symptom is breast cancer. In some embodiments, the disease or symptom is gallbladder cancer. In some embodiments, the disease or symptom is cervical cancer. In some embodiments, the disease or symptom is thyroid cancer. In some embodiments, the disease or symptom is prostate cancer. In some embodiments, the disease or symptom is skin cancer (e.g., squamous cell carcinoma of the skin). In some embodiments, the disease or symptom is a solid tumor. In some embodiments, the disease or symptom is gastric cancer. In some embodiments, the disease or symptom is hepatocellular carcinoma. In some embodiments, the disease or symptom is peripheral nerve sheath tumor. In some embodiments, the disease or symptom is pulmonary hypertension.

[0381] In some embodiments, the disease is cancer associated with a viral infection. In some embodiments, the disease is cancer caused by an infection with an oncogenic virus. In some embodiments, the oncogenic virus is hepatitis A, hepatitis B, hepatitis C, human T-lymphotropic virus (HTLV), human papillomavirus (HPV), Kaposi's sarcoma-associated herpesvirus (HHV-8), Merkel cell polyomavirus, or Epstein-Barr virus (EBV). In some embodiments, the disease is human T-lymphotropic virus. In some embodiments, the disease is Kaposi's sarcoma-associated herpesvirus. In some embodiments, the disease is Epstein-Barr virus. Leukemias and lymphomas that may be associated with oncogenic viruses include: for HTLV, adult T-cell leukemia; for HHV-8, Kassman disease and primary exudative lymphoma; for EBV, Burkitt lymphoma, Hodgkin's lymphoma, and post-transplant lymphoproliferative disorders.

[0382] In some embodiments, the disease or condition is an inflammatory condition or an allergic condition. In some embodiments, the disease or condition is an inflammatory condition such as autoimmune diseases, chronic inflammatory diseases, acute inflammatory diseases, autoinflammatory diseases, fibrotic diseases, metabolic diseases, tumor formation, cardiovascular or cerebrovascular diseases, and the excessive inflammatory response driven by myeloid cells in COVID-19 infection. In some embodiments, the disease or condition is an allergic condition such as asthma and allergic rhinitis.

[0383] In some embodiments, the disease or symptom is a tissue disease or condition, as well as a systemic disease [e.g., systemic lupus erythematosus (SLE); immune thrombocytopenic purpura (ITP); autoimmune hemolytic anemia (AHA); autoimmune neutropenia (AIN); Evans syndrome; proliferative and hyperproliferative disorders such as cancer, atherosclerosis, rheumatoid arthritis, psoriasis, idiopathic pulmonary fibrosis, scleroderma, cirrhosis; and acquired immunodeficiency syndrome (AIDS)]. In some embodiments, the disease or symptom is an immune-mediated disease, such as allogeneic graft rejection (e.g., rejection of transplanted organs or tissues). In some embodiments, the disease or symptom is tissue damage (e.g., associated with organ transplantation or revascularization surgery). In some embodiments, the disease or symptom is a respiratory disease or condition (e.g., asthma). In some embodiments, the disease or symptom is allergic rhinitis. In some embodiments, the disease or symptom is a disease or condition of the bones and joints (e.g., arthritis, rheumatoid arthritis). In some embodiments, the disease or symptom is a skin disease or condition. In some embodiments, the disease or symptom is a gastrointestinal disease or condition.

[0384] Exemplary respiratory diseases include, but are not limited to, those described herein. In some embodiments, the disease or symptom is a reversible obstructive airway disease, such as asthma (e.g., bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma, and dust asthma). In some embodiments, the disease or symptom is chronic or refractory asthma (e.g., late-stage asthma with airway hyperresponsiveness). In some embodiments, the disease or symptom is bronchitis. In some embodiments, the disease or symptom is a symptom characterized by inflammation of the nasal mucosa. In some embodiments, the disease or symptom is acute rhinitis. In some embodiments, the disease or symptom is allergic rhinitis. In some embodiments, the disease or symptom is atrophic rhinitis. In some embodiments, the disease or symptom is chronic rhinitis (e.g., caseous rhinitis, hypertrophic rhinitis, purulent rhinitis, dry rhinitis, and drug-induced rhinitis). In some embodiments, the disease or symptom is membranous rhinitis (e.g., groborrhea rhinitis, fibrinous rhinitis, pseudomembranous rhinitis, and scrofula). In some embodiments, the disease or symptom is seasonal rhinitis [e.g., neurogenic rhinitis (hay fever), vasomotor rhinitis, sarcoidosis, farmer's lung, and related diseases such as fibrotic lung and idiopathic interstitial pneumonia].

[0385] Exemplary bone and joint diseases include, but are not limited to, those described herein. In some embodiments, the disease or condition includes pannus formation. In some embodiments, the disease or condition does not include pannus formation. In some embodiments, the disease or condition is rheumatoid arthritis. In some embodiments, the disease or condition is seronegative spondyloarthritis (e.g., ankylosing spondylitis, psoriatic arthritis, and Reiter's disease). In some embodiments, the disease or condition is Behçet's disease. In some embodiments, the disease or condition is Sjögren's syndrome. In some embodiments, the disease or condition is systemic sclerosis.

[0386] Exemplary skin diseases and conditions include, but are not limited to, those described herein. In some embodiments, the disease or condition is psoriasis. In some embodiments, the disease or condition is systemic sclerosis. In some embodiments, the disease or condition is dermatitis. In some embodiments, the disease or condition is atopic dermatitis. In some embodiments, the disease or condition is contact dermatitis. In some embodiments, the disease or condition is eczematous dermatitis. In some embodiments, the disease or condition is seborrheic dermatitis. In some embodiments, the disease or condition is lichen planus. In some embodiments, the disease or condition is pemphigus. In some embodiments, the disease or condition is bullous pemphigus. In some embodiments, the disease or condition is bullous epidermolysis bullosa. In some embodiments, the disease or condition is urticaria. In some embodiments, the disease or condition is angioedema. In some embodiments, the disease or condition is vasculitis. In some embodiments, the disease or condition is erythema. In some embodiments, the disease or symptom is cutaneous eosinophilia. In some embodiments, the disease or symptom is uveitis. In some embodiments, the disease or symptom is hair loss. In some embodiments, the disease or symptom is alopecia areata. In some embodiments, the disease or symptom is alopecia areata. In some embodiments, the disease or symptom is vernal conjunctivitis.

[0387] Exemplary gastrointestinal diseases and conditions include, but are not limited to, those described herein. In some embodiments, the disease or condition is celiac disease. In some embodiments, the disease or condition is proctitis. In some embodiments, the disease or condition is eosinophilic gastroenteritis. In some embodiments, the disease or condition is mastocytosis. In some embodiments, the disease or condition is pancreatitis. In some embodiments, the disease or condition is Crohn's disease. In some embodiments, the disease or condition is ulcerative colitis. In some embodiments, the disease or condition is a food-related allergy (e.g., migraine, rhinitis, and eczema) affecting areas far from the intestines.

[0388] Exemplary other tissue diseases and conditions, as well as systemic diseases, include, but are not limited to, those described herein. In some embodiments, the disease or condition is multiple sclerosis. In some embodiments, the disease or condition is atherosclerosis. In some embodiments, the disease or condition is acquired immunodeficiency syndrome (AIDS). In some embodiments, the disease or condition is lupus. In some embodiments, the disease or condition is lupus erythematosus. In some embodiments, the disease or condition is systemic lupus erythematosus. In some embodiments, the disease or condition is Hashimoto's thyroiditis. In some embodiments, the disease or condition is myasthenia gravis. In some embodiments, the disease or condition is type 1 diabetes mellitus. In some embodiments, the disease or condition is nephrotic syndrome. In some embodiments, the disease or condition is eosinophilic fasciitis. In some embodiments, the disease or condition is hyperIgE syndrome. In some embodiments, the disease or condition is lepromatous leprosy. In some embodiments, the disease or condition is Cezari syndrome. In some embodiments, the disease or symptom is idiopathic thrombocytopenic purpura. In some embodiments, the disease or symptom is restenosis after angioplasty. In some embodiments, the disease or symptom is a tumor (e.g., leukemia, lymphoma). In some embodiments, the disease or symptom is atherosclerosis.

[0389] Exemplary allogeneic graft rejections include, but are not limited to, those described herein. In some embodiments, the disease or symptom is acute or chronic allogeneic graft rejection (e.g., after a kidney, heart, liver, lung, bone marrow, skin, or cornea transplant). In some embodiments, the disease or symptom is chronic allogeneic graft rejection (e.g., after a kidney, heart, liver, lung, bone marrow, skin, or cornea transplant). In some embodiments, the disease or symptom is chronic graft-versus-host disease.

[0390] In some embodiments, the disease or symptom is an acute inflammatory condition. In some embodiments, the disease or symptom is an autoinflammatory condition. In some embodiments, the disease or symptom is a fibrotic condition. In some embodiments, the disease or symptom is a metabolic condition. In some embodiments, the disease or symptom is tumor formation. In some embodiments, the disease or symptom is a cardiovascular or cerebrovascular condition. In some embodiments, the disease or symptom is an excessive inflammatory response driven by myeloid cells in COVID-19 infection.

[0391] In some embodiments, the disease or symptom is ...

Claims

1. A compound represented by formula I: (I) Or its pharmaceutically acceptable salt; wherein: A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 5-6-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur; A 2 is a 4-8 membered saturated or partially unsaturated heterocyclylidene group containing 1 heteroatom selected from nitrogen and oxygen, a 6 membered saturated or partially unsaturated carbocyclylidene group, a 5-8 membered saturated bicyclylidene group, or a covalent bond, wherein the heterocyclylidene, carbocyclylidene and bicyclylidene groups are substituted with 0 or 1 occurrence of R 3 substituent; A 3 is phenylene substituted with 0 or 1 occurrence R 3 substituted with 0 or 1 occurrence R R 1A , R 1B , and R 1C each independently represents, at each occurrence, hydrogen or C 1-4 alkyl; R 2 independently at each occurrence represents halo, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 alkyl or C 1-4 hydroxyalkyl; R 3 independently for each occurrence represents halo or C 1-4 alkyl; Z is one of the following: a) -C(O)R 4 , -C(O)-(C 1-4 alkylene)-R 4 , -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 , -C(O)-(C 1-4 alkylene)-O-(C 1-4 alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 9 cycloalkyl substituted with z occurrences of R 3-8 ), -C(O)-(azetidinyl, pyrrolidinyl, or piperidinyl wherein each is substituted with one C 1-4 alkyl and one -OH), or -C(O)-(C 1A cycloalkyl substituted with one -N(R 1-6 )-S(O)2-(C 1A alkyl) or -N(R 1-6 )-C(O)-(C 3-7 alkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 , -C(O)-C(O)-OH, -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl) or -N(R 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl); i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replace; or j) Hydrogen; R 4 It is C 1-6 Hydroxyl group, 3-7 saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, 5-7 bis-oxo-heterocyclic group or 3-7 saturated carbocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups. R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), C 1-6 Alkoxy, -(C 1-6 alkylene)-N(R 1A (R) 1B ) or -(C 1-6 alkylene)-N(R 1A )-C(O)-O-(C 1-6 alkyl); R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl, C 1-4 Halogenated alkyl or -(C 1-4 alkylene)-(C 1-4 Alkyl groups); R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ), -(C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 ; R 8 It is C 1-4 Alkyl or -(C 0-4 alkylene)-(phenyl); R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C 1-4 alkyl); m and n are independently 1 or 2; p is 0, 1, 2, 3 or 4; x is 1, 2, 3, 4, or 5; and y and z are independently 1, 2, or 3; The condition is when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

2. The compound of claim 1, wherein A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 6-membered heteroaryl ring containing one or two nitrogen heteroatoms.

3. The compound of claim 1 or 2, wherein m and n are 1.

4. The compound according to any one of claims 1-3, wherein A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbonyl group, or a 5-8-membered saturated bridged bicyclic carbonyl group containing one nitrogen atom, each of which is separated by 0 or 1 R atoms. 3 replace.

5. The compound according to any one of claims 1-4, wherein A 3 Is it an R that appears 0 or 1 times? 3 Substituted p-phenylene.

6. The compound according to any one of claims 1-5, wherein the compound is a compound of formula I.

7. The compound according to any one of claims 1-5, wherein the compound is represented by formula IB: (IB) Or its pharmaceutically acceptable salt; wherein: A 1 It is R that appears in p times. 2 Replacement R appears 1, 2 or 3 times 2 Replacement Or by 2, 3 or 4 R occurrences 2 Replacement ; A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbonyl group, or a 5-8-membered saturated bridged bicyclic carbonyl group containing one nitrogen atom, each of which is separated by 0 or 1 R atoms. 3 replace; R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 alkyl; R 2 Each time it appears, it independently represents halogenation or C. 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 3 Is it halogenated or C 1-4 alkyl; Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 , -C(O)-C(O)-OH, -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl) or -N(R 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl); i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replace; or j) Hydrogen; R 4 It is C 1-6 Hydroxyl group, 3-7 saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, 5-7 bis-oxo-heterocyclic group or 3-7 saturated carbocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups. R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), C 1-6 Alkoxy, -(C 1-6 alkylene)-N(R 1A (R) 1B ) or -(C 1-6 alkylene)-N(R 1A )-C(O)-O-(C 1-6 alkyl); R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl, C 1-4 Halogenated alkyl or -(C 1-4 alkylene)-(C 1-4 Alkyl groups); R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ), -(C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 ; R 8 It is C 1-4 Alkyl or -(C 0-4 alkylene)-(phenyl); R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C 1-4 alkyl); p is 0, 1, 2, 3 or 4; x is 1, 2, 3, 4, or 5; and y and z are 1, 2 or 3 independently.

8. The compound of claim 7, wherein the compound is a compound of formula IB.

9. The compound according to any one of claims 1-8, wherein A 2 yes or Each of them is represented by 0 or 1 occurrences of R. 3 Replace, where A 2 The nitrogen atom is attached to Z.

10. The compound according to any one of claims 1-8, wherein A 2 yes or , where saturated carbon is bonded to Z, where A 2 R appears 0 or 1 times 3 replace.

11. The compound according to any one of claims 1-8, wherein A 2 Is it an R that appears 0 or 1 times? 3 Replacement .

12. The compound according to any one of claims 1-8, wherein A 2 Is it an R that appears 0 or 1 times? 3 Replacement .

13. A compound represented by formula IC: (IC) Or its pharmaceutically acceptable salt; wherein: A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 6-membered heteroaryl ring containing one or two nitrogen atoms; A 2 It is a 5-8 member saturated bridged bicyclic subcarbonyl group or a 5-8 member saturated or partially unsaturated bridged bicyclic subheterocyclic group containing one heteroatom selected from nitrogen and oxygen, each of which is separated by 0 or 1 R. 3 replace; R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 alkyl; R 2 Each time it appears, it independently represents halogenation or C. 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 3 Is it halogenated or C 1-4 alkyl; Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-O-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 , -C(O)-C(O)-OH, -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl) or -N(R 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl); i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A Replace; or j) Hydrogen; R 4 It is C 1-6 Hydroxyl group, 3-7 saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, 5-7 bis-oxo-heterocyclic group or 3-7 saturated carbocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups. R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), C 1-6 Alkoxy, -(C 1-6 alkylene)-N(R 1A (R) 1B ) or -(C 1-6 alkylene)-N(R 1A )-C(O)-O-(C 1-6 alkyl); R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl, C 1-4 Halogenated alkyl or -(C 1-4 alkylene)-(C 1-4 Alkyl groups); R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ), -(C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 ; R 8 It is C 1-4 Alkyl or -(C 0-4 alkylene)-(phenyl); R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C 1-4 alkyl); p is 0, 1, 2, 3 or 4; x is 1, 2, 3, 4, or 5; and y and z are 1, 2 or 3 independently.

14. The compound of claim 13, wherein the compound is a compound of formula C1.

15. The compound of claim 13 or 14, wherein A 2 Is it an R that appears 0 or 1 times? 3 Replacement .

16. The compound according to any one of claims 1-5, wherein the compound is represented by formula ID: (ID) Or its pharmaceutically acceptable salt; wherein: A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 6-membered heteroaryl ring containing one or two nitrogen atoms; A 2 It is a 6-membered saturated or partially unsaturated monocyclic heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbocyclic group, or a 5-8-membered saturated bridged bicyclic carbocyclic group containing one nitrogen atom, wherein the heterocyclic group, monocyclic carbocyclic group, and bicyclic carbocyclic group are separated by 0 or 1 R atoms. 3 replace; R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 alkyl; R 2 Each time it appears, it independently represents halogenation or C. 1-4 Haloalkyl, C 1-4 Alkoxy, C 1-4 Alkyl or C 1-4 Hydroxyalkyl; R 3 Is it halogenated or C 1-4 alkyl; Z is one of the following: a) -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 Alkyl), -C(O)-N(R) 1A )-(C 1-4 Halogenated alkyl groups), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 ; c) -C(O)-C(O)-N(R 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 -C(O)-C(O)-OH, -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted nitrogen-containing heterocyclic butyl, pyrrolidinyl, or piperidinyl); f) -N(R 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 or -N(R) 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ); h) -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl); or i) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A replace; R 4 It is C 1-6 Hydroxyl group, 3-7 saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, 5-7 bis-oxo-heterocyclic group or 3-7 saturated carbocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups. R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), C 1-6 Alkoxy, -(C 1-6 alkylene)-N(R 1A (R) 1B ) or -(C 1-6 alkylene)-N(R 1A )-C(O)-O-(C 1-6 alkyl); R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl, C 1-4 Halogenated alkyl or -(C 1-4 alkylene)-(C 1-4 Alkyl groups); R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ), -(C 0-6 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -N(R) 1B )-C(O)-OR 8 ; R 8 It is C 1-4 Alkyl or -(C 0-4 alkylene)-(phenyl); R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C 1-4 alkyl); p is 0, 1, 2, 3 or 4; x is 1, 2, 3, 4, or 5; and z is 1, 2, or 3; The condition is when B 1 Is it an R that appears 0 or 1 times? 2 Substituted 6-membered aryl ring or B 1 It is R that appears 0 times 2 Replacement When Z is not -C(O)R 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

17. The compound of claim 16, wherein the compound is a compound of formula ID.

18. The compound of claim 16 or 17, wherein A 2 yes or Each of them is represented by 0 or 1 occurrences of R. 3 Replace, where A 2 The nitrogen atom is attached to Z.

19. The compound of claim 16 or 17, wherein A 2 yes or , where saturated carbon is bonded to Z, where A 2 R appears 0 or 1 times 3 replace.

20. The compound of claim 16 or 17, wherein A 2 Is it an R that appears 0 or 1 times? 3 Replacement .

21. The compound of claim 16 or 17, wherein A 2 Is it an R that appears 0 or 1 times? 3 Replacement .

22. The compound according to any one of claims 1-6 or 13-21, wherein A 1 It is R that appears in p times. 2 Replacement .

23. The compound according to any one of claims 1-6 or 13-21, wherein A 1 yes or .

24. The compound according to any one of claims 1-21, wherein A 1 Is it the 2, 3 or 4 occurrences of R? 2 Replacement .

25. The compound according to any one of claims 1-21, wherein A 1 yes or .

26. The compound according to any one of claims 1-21, wherein A 1 Is it the 1, 2 or 3 occurrences of R? 2 Replacement .

27. The compound according to any one of claims 1-21, wherein A 1 yes .

28. The compound according to any one of claims 1-21, wherein A 1 It is R that appears in p times. 2 Replacement .

29. The compound according to any one of claims 1-21, wherein A 1 yes .

30. The compound according to any one of claims 1-22 or 28, wherein p is 1, 2 or 3.

31. The compound according to any one of claims 1-30, wherein R 2 Each occurrence indicates halogenation independently.

32. The compound according to any one of claims 1-30, wherein R 2 It is fluorinated.

33. The compound according to any one of claims 1-6 or 13-21, wherein A 1 yes or .

34. The compound according to any one of claims 1-21, wherein A 1 yes or .

35. The compound according to any one of claims 1-21, wherein A 1 yes .

36. The compound according to any one of claims 1-21, wherein A 1 yes .

37. The compound according to any one of claims 1-36, wherein A 2 R appearing 0 times 3 replace.

38. The compound according to any one of claims 1-37, wherein Z is one of the following: a) -C(O)-(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl) or -C(O)- (with a -N(R) 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 cycloalkyl); b) -C(O)-N(R 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl) or -C(O)-N(R 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl); c) -C(O)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl) or -C(O)-C(O)-(C 1-6 hydroxyalkyl); d) -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl); e) -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl); f) -N(R 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl) or -N(R) 1A )-S(O)2-R 7 ; g) -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A )-C(O)-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-O-(C 1-6 Alkyl); or h) A 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A replace.

39. The compound according to any one of claims 1-37, wherein Z is -C(O)R 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

40. The compound according to any one of claims 1-37, wherein Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-(C 1-4 alkylene)-N(R 1A )-S(O)2-(C 1-4 alkyl) or -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-R 4 .

41. The compound according to any one of claims 1-40, wherein R 4 It is C 1-6 Hydroxyalkyl.

42. The compound according to any one of claims 1-37, wherein Z is -C(O)-(C 1-4 alkylene)-N(R 1A )-C(O)-(R appearing z times) 9 Replacement C 3-8 cycloalkyl), -C(O)- (each of which is separated by a C 1-4 Alkyl and a -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl) or -C(O)- (with a -N(R)- 1A )-S(O)2-(C 1-6 alkyl) or -N(R) 1A )-C(O)-(C 1-6 alkyl) substituted C 3-7 (cycloalkyl).

43. The compound according to any one of claims 1-37, wherein Z is -C(O)-N(R) 1A )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-N(R) 1A )-(C 1-6 alkyl) or -C(O)-N(R 1A )-(C 1-4 (Halogenated alkyl groups).

44. The compound according to any one of claims 1-37, wherein Z is -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] x -(C 1-6 alkoxy group), -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1B )-S(O)2-R 6 -C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 Alkyl), -C(O)-N(R) 1A )-(C 0-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -C(O)-N(R 1A )-(C 1-4 alkylene)-(C 3-7 cycloalkyl) or -C(O)-N(R 1A )-S(O)2-R 7 。 45. The compound according to any one of claims 1-37, wherein Z is -C(O)-C(O)-N(R) 1A )-R 5 -C(O)-C(O)-N(R) 1A (R) 1B -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-4 Alkyl), -C(O)-C(O)-N(R) 1A )-S(O)2-(C 1-6 Alkyl), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl group containing 1-4 nitrogen atoms), -C(O)-C(O)-R 4 Or -C(O)-C(O)-OH.

46. ​​The compound according to any one of claims 1-37, wherein Z is -C(O)-C(O)-N(R) 1A )-(C 1-6 (hydroxyalkyl).

47. The compound according to any one of claims 1-37, wherein Z is -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl) or -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 replace).

48. The compound according to any one of claims 1-37, wherein Z is -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-C(O)-N(R 1B )-(C 1-4 alkylene)-N(R 1C )-C(O)-(C 1-4 alkyl) or -N(R) 1A )-C(O)-C(O)-N(R 1B )-(C 1-6 alkylene)-N(R 1C )-S(O)2-(C 1-4 alkyl).

49. The compound according to any one of claims 1-37, wherein Z is -N(R 1A )-C(O)-N(R 1B )-(C replaced by 0 or 1 halogenation) 1-6 hydroxyalkyl), -N(R) 1A )-C(O)-N(R 1B (R) 1C ), -N(R 1A )-C(O)-N(R 1B )-(C 1-4 Halogenated alkyl), -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-(C 1-4 alkylene)-(tetrahydrofuranyl or tetrahydropyranyl), -N(R 1A -C(O)-(morpholinyl) or -N(R) 1A )-C(O)-(each of which is controlled by a C 1-4 Alkyl and an -OH-substituted azahexacyclic butyl, pyrrolidinyl, or piperidinyl).

50. The compound according to any one of claims 1-37, wherein Z is -N(R 1A )-C(O)-N(R 1B )-(C 1-6 (hydroxyalkyl).

51. The compound according to any one of claims 1-37, wherein Z is -N(R 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-C(O)-(C 1-4 alkyl), -N(R) 1A )-C(O)-(C 1-4 alkylene)-N(R 1B )-S(O)2-(C 1-4 alkyl) or -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 .

52. The compound according to any one of claims 1-37, wherein Z is -N(R 1A )-S(O)2-R 7 .

53. The compound according to any one of claims 1-37, wherein Z is -S(O)2-(C 1-6 hydroxyalkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy), -S(O)2-(C 1-4 alkylene)-C(O)-O-(C 1-6 Alkyl), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -S(O)2-N(R) 1A )-(C 1-6 hydroxyalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 alkyl) or -S(O)2-N(R 1A )-C(O)-N(R 1B (R) 1C ).

54. The compound according to any one of claims 1-37, wherein Z is -(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-N(R 1A )-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -(C 1-4 alkylene)-C(O)-OH or -(C 1-4 alkylene)-C(O)-O-(C 1-6 alkyl).

55. The compound of any one of claims 1-37, wherein Z is a 5-membered oxo-heterocyclic group containing two independently selected cyclic heteroatoms chosen from nitrogen and oxygen, wherein the oxo-heterocyclic group is separated by an R 1A replace.

56. The compound according to any one of claims 1-37, wherein Z is -S(O)2-(C 1-6 (hydroxyalkyl).

57. The compound according to any one of claims 1-37, wherein Z is , , , , , , , , , , , , , , , , , , , , , or .

58. The compound according to any one of claims 1-37, wherein Z is .

59. The compound according to any one of claims 1-37, wherein Z is or .

60. The compound according to any one of claims 1-37, wherein Z is , , , or .

61. The compound according to any one of claims 1-37, wherein Z is .

62. The compound according to any one of claims 1-55, wherein R 1A R 1B and R 1C It is hydrogen.

63. A compound represented by formula I-1: (I-1) Or its pharmaceutically acceptable salt; wherein: A 1 It is R that appears in p times. 2 Replacement B 1 It is a 6-membered aryl ring or a 5-6-membered heteroaryl ring containing one or two heteroatoms independently selected from nitrogen and sulfur; A 2 It is a 6-membered saturated or partially unsaturated heterocyclic group, a 6-membered saturated or partially unsaturated monocyclic carbocyclic group, a 5-8-membered saturated bicyclic carbocyclic group, or a covalent bond containing one heteroatom selected from nitrogen, wherein the heterocyclic group, monocyclic carbocyclic group, and bicyclic carbocyclic group are separated by 0 or 1 R atoms. 3 replace; R 1A R 1B and R 1C Each time it appears, it independently represents either hydrogen or carbon. 1-4 alkyl; R 2 Each occurrence independently represents halogenation; R 3 Is it halogenated or C 1-4 alkyl; Z is -C(O)R 4 -C(O)-(C 1-4 (alkylene)-R 4 -C(O)-OH, -C(O)-O-(C 1-6 Alkyl), -C(O)-N(R) 1A (R) 1B ), -C(O)-O-(C 1-4 alkylene)-O-(C 1-4 alkylene)-N(R 1A (R) 1B -C(O)-O-(with 1 occurrence of -N(R) 1A (R) 1B ) replaced by C 1-4 alkylene)-(C 1-4 hydroxyalkyl), -S(O)2-(C 1-6 Alkyl), -S(O)2-(C 3-7 cycloalkyl), -S(O)2-N(R 1A (R) 1B -S(O)2-N(R) 1A )-C(O)-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-O-(C 1-6 Alkyl), -S(O)2-N(R) 1A )-C(O)-N(R 1B (R) 1C ), -S(O)2-[(C 1-4 [alkylene]-O-] x -R 5 -N(R) 1A )-C(O)-(C 1-4 alkylene group (5-6 membered saturated heterocyclic group containing 1 oxygen atom), -N(R 1A )-C(O)-O-(C 1-4 alkylene)-(phenyl), -N(R) 1A )-C(O)-O-[(C 1-4 [alkylene]-O-] x -R 6 -N(R) 1A )-C(O)-N(R 1B )-[(C 1-4 [alkylene]-O-] x -R 6 -C(O)-N(R) 1A )-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-(C 1-4 alkylene)-O-(C 1-6 hydroxyalkyl), -C(O)-N(R) 1A )-[(C 1-4 [alkylene]-O-] x -(C 1-4 alkylene)-N(R 1A (R) 1B ), -N(R 1A )-C(O)-N(R 1B )-[(C 1-6 hydroxyalkyl), -C(O)-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy group), -C(O)N(R 1B )-(C 1-4 alkylene)-[O-(C 1-4 alkylene)-] y -(C 1-6 alkoxy group, -C(O)-C(O)-OH, -C(O)-C(O)-N(R) 1A (R) 1B ), -N(R 1A )-C(O)-(C 1-6 hydroxyalkyl), -C(O)-C(O)-N(R) 1A )-R 5 -N(R) 1A )-C(O)-C(O)-N(R 1B (R) 1C ), -C(O)-N(R) 1A )-S(O)2-R 7 -N(R) 1A )-S(O)2-R 7 -N(R) 1A )-S(O)2-N(R 1B )-CO2-(C 1-4 alkylene)-phenyl, -C(O)-C(O)-N(R 1A )-S(O)2-(C 1-6 Alkyl), -S(O)2-(C 1-4 alkylene)-(C 1-6 alkoxy group), -C(O)-C(O)-N(R) 1A )-(C 1-4 alkylene)-(5-membered heteroaryl containing 1-4 nitrogen atoms), -C(O)-O-(C 1-4 Alkylene)-(a 5-membered saturated heterocyclic group containing 1 nitrogen atom and 1 oxygen atom, wherein the heterocyclic group is composed of z R atoms appearing in the form of alkylene groups) 9 (Substitution) or hydrogen; R 4 It is C 1-6 Hydroxyl group, 3-7 saturated heterocyclic group containing one or two heteroatoms independently selected from nitrogen and oxygen, 5-7 bis-oxo-heterocyclic group or 3-7 saturated carbocyclic group containing one or two heteroatoms independently selected from sulfur, nitrogen and oxygen, wherein the heterocyclic group and carbocyclic group are substituted by 0 or 1 hydroxyl groups. R 5 It is C 1-6 Alkyl, C 1-6 Hydroxyalkyl, -(C 1-4 alkylene)-(C 1-4 alkoxy) or C 1-6 Alkoxy; R 6 It is C 1-4 Alkyl, C 1-4 Hydroxyalkyl or C 1-4 Halogenated alkyl groups; R 7 It is C 1-4 Alkyl, C 1-4 Alkoxy, -(C 1-4 alkylene)-(C 1-4 alkoxy), -(C 0-4 alkylene)-N(R 1A (R) 1B ) or -N(R 1B )-C(O)-OR 8 ; R 8 It is C 1-4 Alkyl or -(C 0-4 alkylene)-(phenyl); R 9 It is oxygen, C 1-4 Alkyl, hydroxyl or -C(O)-O-(C 1-4 alkyl); m is 1 or 2; n is 1 or 2; p is 0, 1, 2, 3 or 4; x is 1, 2, 3, 4, or 5; and y and z are independently 1, 2, or 3; The condition is when B 1 Is it an R that appears 0 or 1 times? 2 When the 6-membered aryl ring is substituted, then Z is not -C(O)R. 4 or -C(O)-(C 1-4 (alkylene)-R 4 .

64. The compound of claim 63, wherein the compound is a compound of formula I-1.

65. The compound of claim 63 or 64, wherein A 1 yes .

66. The compound of claim 63 or 64, wherein A 1 yes .

67. The compound according to any one of claims 63-66, wherein A 2 yes , , , , , Each of them is represented by 0 or 1 occurrences of R. 3 Replacement, or covalent bond, where *** is the connection point with Z.

68. The compound of claim 63, wherein the compound is a compound of formula Id: (Id) Or a pharmaceutically acceptable salt thereof, wherein X is -C(H)- or -N-.

69. The compound according to any one of claims 63-68, wherein A 2 yes or Each of them is represented by 0 or 1 occurrences of R. 3 Replace, where *** is the connection point with Z.

70. The compound according to any one of claims 63-69, wherein Z is , , , , , , , , , , , or .

71. The compound according to any one of claims 63-69, wherein Z is .

72. A compound listed in Table 1 of this document, or a pharmaceutically acceptable salt thereof.

73. The compound of claim 72, wherein the compound is one of the compounds listed in the table below, or a pharmaceutically acceptable salt thereof: 。 74. A pharmaceutical composition comprising a compound as described in any one of claims 1-73 and a pharmaceutically acceptable carrier.

75. A method of treating a disease or condition mediated by NAMPT, comprising administering a therapeutically effective amount of the compound as described in any one of claims 1-73 to a subject in need of treating the disease or condition.

76. The method of claim 75, wherein the NAMPT-mediated disease or symptom is a proliferative condition.

77. The method of claim 75, wherein the disease or symptom mediated by NAMPT is an inflammatory condition.

78. The method of claim 75, wherein the NAMPT-mediated disease or symptom is a metabolic disorder.

79. The method of claim 75, wherein the disease or condition mediated by NAMPT is selected from cancer, tumor formation, chronic inflammatory conditions, acute inflammatory conditions, autoinflammatory conditions, metabolic conditions, and combinations thereof.

80. The method of claim 75, wherein the disease or symptom mediated by NAMPT is cancer.

81. The method of claim 80, wherein the cancer is pancreatic cancer, melanoma, glioma, lung cancer, colon cancer, rectal cancer, breast cancer, cervical cancer, prostate cancer, gastric cancer, skin cancer, liver cancer, bile duct cancer, nervous system cancer, lymphoma, leukemia, ovarian cancer, uterine cancer, endometrial cancer, testicular cancer, brain cancer, oral cancer, esophageal cancer, head and neck cancer, gastric cancer, sebaceous gland cancer, gallbladder cancer, bladder cancer, urethral cancer, kidney cancer, eye cancer, thyroid cancer, urothelial carcinoma, colorectal cancer, or glioblastoma multiforme.

82. The method of claim 80, wherein the cancer is thyroid cancer, duodenal cancer, neuroendocrine carcinoma (NEC), uterine cancer, small cell lung cancer (SCLC), hepatocellular carcinoma, mesothelioma, breast cancer, sarcoma, ovarian cancer, renal cell carcinoma, rectal cancer, head and neck cancer, prostate cancer, pancreatic cancer, melanoma, colorectal cancer, cervical cancer, non-small cell lung cancer (NSCLC), cholangiocarcinoma, or endometrial cancer.

83. The method of any one of claims 79-82, wherein the cancer is a NAPRT-negative cancer.

84. The method of claim 75, wherein the disease or condition mediated by NAMPT is allergic rhinitis, nasal inflammation, asthma, chronic obstructive pulmonary disease (COPD), bronchitis, emphysema, chronic eosinophilic pneumonia, adult respiratory distress syndrome, sinusitis, allergic conjunctivitis, idiopathic pulmonary fibrosis, atopic dermatitis, asthma, allergic rhinitis, arthritis, inflammatory bowel disease, Crohn's disease, ulcerative colitis, multiple sclerosis, endometriosis, eczema, psoriasis, rosacea, or lupus.

85. The method of claim 75, wherein the NAMPT-mediated disease or condition is multiple sclerosis, ankylosing spondylitis, arthritis, osteoarthritis, juvenile arthritis, reactive arthritis, rheumatoid arthritis, psoriatic arthritis, acquired immunodeficiency syndrome (AIDS), celiac disease, psoriasis, chronic graft-versus-host disease, acute graft-versus-host disease, Crohn's disease, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, stomatitis diarrhea, etc. Primary thrombocytopenic purpura, myasthenia gravis, Sjögren's syndrome, scleroderma, ulcerative colitis, asthma, uveitis, rosacea, dermatitis, alopecia areata, vitiligo, arthritis, type 1 diabetes mellitus, lupus erythematosus, systemic lupus erythematosus, Hashimoto's thyroiditis, myasthenia gravis, nephrotic syndrome, eosinophilic fasciitis, hyperIgE syndrome, lepromatous leprosy, Cezari syndrome, idiopathic thrombocytopenic purpura, restenosis after angioplasty, tumors, or atherosclerosis.

86. The method of claim 75, wherein the disease or condition mediated by NAMPT is psoriasis, dermatitis, vitiligo, ichthyosis, alopecia areata, epidermolysis bullosa, hidradenitis suppurativa, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, psoriatic arthritis, systemic lupus erythematosus, or kidney disease.

87. The method of claim 75, wherein the disease or symptom mediated by NAMPT is inflammatory bowel disease (IBD).

88. The method of claim 75, wherein the disease or symptom mediated by NAMPT is an autoimmune disease or atherosclerosis.

89. The method of any one of claims 75-88, wherein the subject is a human.

90. A method for inhibiting the activity of NAMPT, comprising contacting NAMPT with an effective amount of the compound as described in any one of claims 1-73 to inhibit the activity of said NAMPT.

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