Quinoline cGAS antagonist compounds

Abstract

The present disclosure provides compounds that are cGAS antagonists, methods of making the compounds, pharmaceutical compositions comprising the compounds, and their use in medical therapy.

Description

1. Background Technology

[0001] Cyclic GMP-AMP synthase (cGAS) (UniProtKB-Q8N884) is an enzyme that acts as a DNA sensor, triggering an immune response against pathogens by activating the interferon gene stimulator (STING) receptor. It has been shown that aberrant activation of cGAS by autologous DNA is a root cause of debilitating and sometimes fatal autoimmune diseases. Knockout studies in animal models have demonstrated that inhibiting cGAS is a promising therapeutic intervention. Furthermore, recent research has shown that the cGAS-STING pathway plays a crucial role in the innate immune response to tumors, and stimulation of this pathway is a promising strategy being clinically tested for cancer immunotherapy.

[0002] There remains a persistent need in this field for effective treatments of autoimmune and autoinflammatory diseases, such as systemic lupus erythematosus (SLE), scleroderma, psoriasis, Aicardi Goutières syndrome (AGS), Sjögren's syndrome, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, diabetes, cardiovascular disease, and neurodegenerative diseases. Therefore, there is still a need to find effective and selective small-molecule inhibitors of cGAS for the treatment of these diseases and other debilitating conditions associated with abnormal cGAS activation. 2. Overview of the Invention

[0004] This disclosure relates to small molecule cGAS antagonist compounds, methods for preparing said compounds, pharmaceutical compositions comprising said compounds, and their use in medical treatment. Specifically, this disclosure provides quinoline cGAS antagonist compounds that can be used as inhibitors of cGAS. An advantage of the compounds provided herein is the wide range of pharmacological activities possible, consistent with cGAS inhibition. Furthermore, this disclosure provides methods for treating inflammatory diseases, allergic diseases, autoimmune diseases, and infectious diseases using the compounds described herein. The compounds can also be used to treat aging or age-related diseases such as neurodegenerative diseases, cardiovascular diseases, liver and kidney diseases, cancer, and premature aging.

[0005] It has now been found that the compounds of this disclosure and pharmaceutically acceptable compositions thereof can effectively inhibit cGAS. Such compounds of this disclosure have the general formula I:

[0006]

[0007] Or its pharmaceutically acceptable salt, wherein each variable is as defined and described herein.

[0008] The compounds disclosed herein and their pharmaceutically acceptable compositions may be used to treat a variety of diseases, disorders, or conditions associated with abnormal activation of cGAS. Such diseases, disorders, or conditions include those described herein.

[0009] The compounds disclosed herein can also be used to study cGAS enzymes in biological and pathological phenomena, and to evaluate, in vitro or in vivo, new cGAS antagonists or other regulators of cGAS, signal transduction pathways and cytokine levels. 3. Detailed Description of the Invention

[0011] In the following disclosure, certain specific details are set forth to provide a thorough understanding of various embodiments. However, those skilled in the art will understand that the methods and uses described herein can be practiced without these details. In other instances, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments. Unless the context otherwise requires, throughout this specification and the following claims, the word “comprise” and its variations such as “comprises” and “comprising” should be interpreted in an open, inclusive sense, meaning “including but not limited to”. Furthermore, the headings provided herein are for convenience only and do not constitute an explanation of the scope or meaning of the claimed invention.

[0012] Throughout this specification, references to "an embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with that embodiment is included in at least one embodiment. Therefore, the phrases "in an embodiment" or "in an embodiment" appearing in different places throughout this specification do not necessarily refer to the same embodiment. Furthermore, the particular feature, structure, or characteristic may be combined in any suitable manner in one or more embodiments. Additionally, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural indicators unless the context clearly indicates otherwise. It should also be noted that the term "or" is generally used in its meaning including "and / or" unless the context clearly indicates otherwise.

[0013] 3.1. Definition

[0014] The compounds disclosed herein include those generally described herein, and are further described by the categories, subclasses and species disclosed herein. As used herein, the following definitions apply unless otherwise indicated. For the purposes of this disclosure, chemical elements are identified according to the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75th edition. 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.

[0015] As used herein, the term "aliphatic" or "aliphatic group" refers to a fully saturated or branched, substituted or unsubstituted, straight-chain (i.e., unbranched) or branched hydrocarbon chain containing one or more unsaturated units, or a fully saturated or non-aromatic monocyclic or bicyclic hydrocarbon (also referred to herein as "carbocyclic," "cycloaliphatic," or "cycloalkyl") having a single connection point to the rest of the molecule. Unless otherwise indicated, an aliphatic group contains 1 to 6 aliphatic carbon atoms. In some embodiments, the aliphatic group contains 1 to 5 aliphatic carbon atoms. In other embodiments, the aliphatic group contains 1 to 4 aliphatic carbon atoms. In still other embodiments, the aliphatic group contains 1 to 3 aliphatic carbon atoms, and in yet still other embodiments, the aliphatic group contains 1 to 2 aliphatic carbon atoms. In some embodiments, "cycloaliphatic" (or "carbocyclic" or "cycloalkyl") refers to a monocyclic C3-C6 hydrocarbon that is fully saturated or contains one or more unsaturated units, but is not aromatic, and has 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 groups and their hybrid concepts such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl, or (cycloalkyl)alkenyl.

[0016] As used herein, the term "bridged bicyclic" refers to any bicyclic system, i.e., carbocyclic or heterocyclic, 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 skeleton atom of the ring system bonded to three or more skeleton atoms (excluding hydrogen). In some embodiments, the bridged bicyclic group has 7 to 12 ring members and 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Such bridged bicyclic groups are well known in the art and include those groups set forth below, wherein each group is attached to the remainder of the molecule at any substituted carbon or nitrogen atom. Unless otherwise indicated, the bridged bicyclic group is optionally substituted with one or more substituents set forth with respect to aliphatic groups. Additionally or alternatively, any substituted nitrogen atom in the bridged bicyclic group is optionally substituted. Exemplary bridged bicyclic groups include:

[0017]

[0018] In some implementations, the bicyclo[1.1.1.]pentane is a phenyl isosteric isoosteric form.

[0019] The term "lower alkyl" indicates C 1-4 Straight-chain or branched alkyl groups. Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0020] The term "lower haloalkyl" refers to a C-aryl group substituted with one or more halogen atoms. 1-4 Straight-chain or branched alkyl groups.

[0021] 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 an oxygen, sulfur, nitrogen, phosphorus or silicon atom in a heterocycle).

[0022] As used in this paper, the term "unsaturated" means that a part has one or more unsaturated units.

[0023] The term "divalent C" used in this article 1-8 (or C 1-6 "Saturated or unsaturated, straight or branched, hydrocarbon chain" refers to a straight or branched divalent alkylene, alkenylene, or alkyne chain as defined herein.

[0024] 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 1-6, 1-4, 1-3, 1-2, or 2-3. The substituted alkylene chain is a polymethylene in which one or more methylene hydrogen atoms are replaced by substituents. Suitable substituents include those described below with respect to substituted aliphatic groups.

[0025] The term "alkenyl" refers to a divalent alkenyl group. A substituted alkenyl chain is a polymethylene chain containing at least one double bond, wherein one or more hydrogen atoms are replaced by a substituent. Suitable substituents include those described below with respect to substituted aliphatic groups.

[0026] As used in this article, the term "cyclopropylene" refers to a divalent cyclopropyl group with the following structure:

[0027] The term "halogen" refers to F, Cl, Br, or I.

[0028] The term "aryl," used alone or as part of a larger portion (such as in "aralkyl," "aralkyloxy," or "aryloxyalkyl"), refers to a monocyclic or bicyclic ring system having a total of 4 to 14 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" is used interchangeably with the term "aryl ring." In some embodiments of this disclosure, "aryl" refers to an aromatic ring system, including but not limited to phenyl, biphenyl, naphthyl, anthracene, etc., which may carry one or more substituents. The scope of the term "aryl" as used herein also includes groups in which an aromatic ring is fused to one or more non-aromatic rings, such as indanyl, phthalimide, naphthimidyl, phenanthridine, or tetrahydronaphthyl.

[0029] The terms "heteroaryl" and "heteroaryl-" used alone or as part of a larger part (e.g., "heteroarylalkyl" or "heteroarylalkoxy") refer to a group that has 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; has 6, 10, or 14 π electrons shared in a ring array; and has 1 to 5 heteroatoms in addition to carbon atoms. The term "heteroatom" in the context of "heteroaryl" specifically includes, but is not limited to, nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, as well as any quaternized form of basic nitrogen. Heteroaryl groups include, but are not limited to, thiophene, furanyl, pyrrole, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridinyl, pyridinyl, pyrazinyl, indazinyl, purine, naphthidyl, and pteridinyl. As used herein, the terms “heteroaryl” and “heteroary-” also include groups in which a heteroaryl ring is fused to one or more aryl, cycloaliphatic, or heterocyclic rings, wherein the residue or linking point is on the heteroaryl ring. Non-limiting examples include indolyl, isoindolyl, benzothiophene, benzofuranyl, dibenzofuranyl, indazole, benzimidazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, terpineyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinazinyl, carbazolyl, acridineyl, phenazinyl, phenthiazolyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-1,4-oxazin-3(4H)-one. Heteroaryl groups can be monocyclic or bicyclic. The heteroaryl ring may include one or more oxo (=O) or thio (=S) substituents. The term “heteroaryl” may be used interchangeably with the terms “heteroaryl ring,” “heteroaryl group,” or “heteroaryl family,” wherein any of these terms includes an optionally substituted ring. The term “heteroarylalkyl” refers to an alkyl group substituted with a heteroaryl group, wherein the alkyl and heteroaryl portions are optionally substituted independently.

[0030] As used herein, the terms “heterocycle,” “heterocyclic group,” “heterocyclic residue,” and “heterocyclic ring” are used interchangeably to refer to a stable 5- to 7-membered monocyclic or 7- to 10-membered bicyclic heterocyclic portion that is saturated or partially unsaturated and has one or more, preferably 1 to 4, heteroatoms as defined above, in addition to a carbon atom. When referring to the ring atom of a heterocycle, the term “nitrogen” includes substituted nitrogen. As an example, a saturated or partially unsaturated ring may have 0 to 3 heteroatoms selected from oxygen, sulfur, or nitrogen.

[0031] Heterocycles may be attached to the provided compound at any heteroatom or carbon atom that produces a stable structure, and any ring atom may optionally be substituted. Examples of such saturated or partially unsaturated heterocyclic residues include, but are not limited to, tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolyl, piperidinyl, pyrrololinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolyl, piperazine, dioxalyl, dioxazolidinyl, diazacyclopentyl, diazacycloheptanetrienyl, oxazacycloheptanetrienyl, thiaazacycloheptanetrienyl, morpholinyl, and quininecycloyl. The terms “heterocycle,” “heterocyclic group,” “heterocyclic ring,” “heterocyclic moiety,” and “heterocyclic residue” are used interchangeably herein and also include groups in which the heterocyclic ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indololinyl, 3H-indolyl, chromanyl, phenanthridineyl, or tetrahydroquinolinyl. The heterocyclic group can be monocyclic, bicyclic, bridged bicyclic, or spirocyclic. The heterocycle may include one or more oxo (=O) or thio (=S) substituents. The term "heterocyclic alkyl" means an alkyl group substituted with a heterocyclic group, wherein the alkyl and heterocyclic portions are optionally substituted independently.

[0032] As used herein, the term "partially unsaturated" means 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.

[0033] As described herein, the compounds of this disclosure may contain a “substituted” portion. Generally, the term “substituted” means that one or more hydrogen atoms of the specified portion are replaced by a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at one or more substituted positions of the group, and the substituents may be the same or different at each position when more than one position in any given structure is replaced by more than one substituent selected from a particular group. The combinations of substituents contemplated in this disclosure are preferably those that result in the formation of stable or chemically viable compounds. The term “stable” as used herein means a compound that is not substantially altered when subjected to conditions that allow it to be produced, detected, and, in some embodiments, recovered, purified, and used for one or more purposes disclosed herein.

[0034] The suitable monovalent substituents on the substituted carbon atoms of the "optionally substituted" group are independently: halogens; -(CH2). 0-6 R o ;-(CH2) 0-6 OR o ;-O(CH2) 0-6 R o ;-O-(CH2) 0-6C(O)OR o ;-(CH2) 0-6 CH(OR o )2;-(CH2) 0- 6SR o ;-(CH2) 0-6 Ph, the Ph can be R o Substitution; -(CH2) 0-6 O(CH2) 0-1 Ph, the Ph can be R o Replacement; -CH=CHPh, where Ph can be replaced by R o Substitution; -(CH2) 0-6 O(CH2) 0-1 -pyridyl group, the pyridyl group can be R o Substitution; -NO2; -CN; -N3; ​​-(CH2) 0-6 N(R o )2;-(CH2) 0-6 N(R o )C(O)R o ;-N(R o )C(S)R o ;-(CH2) 0-6 N(R o )C(O)NR o 2; -N(R) o )C(S)NR o 2;-(CH2) 0-6 N(R o )C(O)OR o ;-N(R o )N(R o )C(O)R o ;-N(R o )N(R o )C(O)NR o 2; -N(R) o )N(R o )C(O)OR o ;-(CH2) 0-6 C(O)R o ;-C(S)R o ;-(CH2) 0-6 C(O)OR o ;-(CH2) 0-6 C(O)SR o ;-(CH2) 0-6 C(O)OSiR o 3; -(CH2) 0-6 OC(O)R o ;-OC(O)(CH2)0-6 SR o 、-(CH2) 0-6 SC(O)R o ;-(CH2) 0-6 C(O)NR o 2; -C(S)NR o 2;-C(S)SR o ;-SC(S)SR o 、-(CH2) 0-6 OC(O)NR o 2; -C(O)N(OR) o )R o ;-C(O)C(O)R o ;-C(O)CH2C(O)R o ;-C(NOR) o )R o ;-(CH2) 0-6 SSR o ;-(CH2) 0-6 S(O)2R o ;-(CH2) 0-6 S(O)2OR o ;-(CH2) 0-6 OS(O)2R o ;-S(O)2NR o 2;-(CH2) 0-6 S(O)R o ;-N(R o )S(O)2NR o 2; -N(R) o )S(O)2R o ;-N(OR o )R o ;-C(NH)NR o 2; -P(O)2R o ;-P(O)R o 2;-P(O)(OR o )2;-OP(O)(R o OR o ;-OP(O)R o 2;-OP(O)(OR o )2; SiR o 3;-(C 1-4 (linear or branched alkylene)ON(R) o )2; or -(C 1-4 linear or branched alkylene) C(O)ON(R o )2, where each R o The following can be substituted and independently defined as: hydrogen, C 1-6Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, -CH2- (5- to 6-membered heteroaryl ring) or a 5- to 6-membered saturated, partially unsaturated or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen or sulfur, or R, although defined above. o The two independent occurrences of these atoms, together with their inserted atoms, form 3 to 12 saturated, partially unsaturated, or aryl monocyclic or bicyclic rings with 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which can be substituted as defined below.

[0035] In R o (or via R) o The appropriate monovalent substituents on the ring formed by the two independent occurrences of these atoms (along with their inserted atoms) are independently halogens, -(CH2). 0-2 R · -(halogenated R) · -(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) 0-2 SH, -(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 · , where each R · It is either unsubstituted or, in the case of "halogenation" preceding it, substituted by only one or more halogens, and independently selected from C. 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, or sulfur. In Ro Suitable divalent substituents on saturated carbon atoms include =O and =S.

[0036] Suitable divalent substituents on the saturated carbon atom of the "optionally substituted" group include the following: =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-, where R * Each independent occurrence of is selected from hydrogen, C 1-6 Aliphatic (which may be substituted as defined below) or an unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents for the substituted carbon atom attached to the "optionally substituted" group include: -O(CR * 2) 2- 3O-, where R * Each independent occurrence of is selected from hydrogen, C 1-6 Aliphatic (which may be substituted as defined below) or an unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, or sulfur.

[0037] In R * Suitable substituents on aliphatic groups include halogens, -R · -(halogenated R) · -OH, -OR · -O (halogenated R) · -CN, -C(O)OH, -C(O)OR · -NH2, -NHR · -NR · 2 or -NO2, where each R · It is either unsubstituted or, in the case of a preceding "halogen", substituted by only one or more halogens, and is independently C. 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0038] Suitable substituents on the substituted nitrogen of the "optionally substituted" group include Each of them are independently hydrogen, C 1-6 Aliphatic (which may be substituted as defined below), unsubstituted -OPh, or unsubstituted 5- to 6-membered saturated, partially unsaturated, or aryl rings having 0 to 4 independent heteroatoms selected from nitrogen, oxygen, or sulfur, or although defined above, The two independent occurrences of these atoms, together with their inserted atoms, form unsubstituted 3 to 12-membered saturated, partially unsaturated, or aryl monocyclic or bicyclic rings with 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0039] exist Suitable substituents on the aliphatic group are independently halogens, -R · -(halogenated R) · -OH, -OR · -O (halogenated R) · -CN, -C(O)OH, -C(O)OR · -NH2, -NHR · -NR · 2 or -NO2, where each R · It is either unsubstituted or, in the case of a preceding "halogen", substituted by only one or more halogens, and is independently C. 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0 to 4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0040] The term “compound provided” as used herein means any of the categories, subcategories and / or types listed herein.

[0041] As used herein, the term "pharmaceutically acceptable salt" means a salt that, within reasonable medical judgment, is suitable for contact with human and lower animal tissues without undue toxicity, irritation, allergic response, etc., and is proportionate to a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, SMBerge et al. described 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 this disclosure include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable, non-toxic acid addition salts are salts formed by amino groups with acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or organic acids such as acetic acid, trifluoroacetic acid (TFA), oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or formed 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, digluconate, dodecyl sulfate, ethanesulfonate, formate, fumarate, glucono-p-gluconate, glyceryl phosphate, gluconate, hemisulfate, heptaate, hexanoate, hydroiodate, 2-hydroxy-ethanesulfonate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pyrate, pectinate, persulfate, 3-phenylpropionate, phosphate, neopentanoate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc. In some embodiments, some of the compounds disclosed herein are prepared as TFA salts.

[0042] Salts derived from suitable bases include alkali metals, alkaline earth metals, ammonium, and nitrogen. + (C 1-4 Alkyl salts. Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, etc. Other pharmaceutically acceptable salts include, where appropriate, non-toxic ammonium, quaternary ammonium, and amine cation salts formed from counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates.

[0043] Unless otherwise stated, the structures described herein are also intended to include all isomers (e.g., enantiomers, diastereomers, and geometric (or conformations)) of the structures; for example, R and S configurations for each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Therefore, single stereochemical isomers of the compounds of the present invention, as well as enantiomers, diastereomers, and geometric (or conformational) mixtures, are within the scope of this disclosure. Unless otherwise stated, all tautomers of the compounds of this disclosure are within the scope of this disclosure. Additionally, unless otherwise stated, the structures depicted herein are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, those having hydrogen replaced by deuterium or tritium, or those having hydrogen replaced by deuterium or tritium. 13 C- or 14 Compounds of the present invention with C-enriched carbon-substituted carbon structures are within the scope of this disclosure. According to this disclosure, such compounds can be used, for example, as analytical tools, probes in bioassays, or therapeutic agents.

[0044] As used herein, the term "antagonist" is defined as a compound that binds to and / or inhibits cGAS with measurable affinity. In some embodiments, the cGAS antagonist has an IC50 and / or binding constant of less than about 30 μM or less than about 2 μM.

[0045] 3.2. Compounds disclosed herein

[0046] The compounds and compositions thereof disclosed herein can be used as cGAS antagonists. In some embodiments, the provided compounds inhibit cGAS.

[0047] This disclosure provides compounds having formula I:

[0048]

[0049] Or its pharmaceutically acceptable salts, of which:

[0050] Ring A is a group that is optionally substituted with a group selected from phenyl, HetAr and HetCy;

[0051] HetAr is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein the 5- to 6-membered heteroaryl ring is not an imidazole or a pyrazole;

[0052] HetCy is a 4- to 7-membered saturated or partially unsaturated heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0053] R 2It is a halogen, -OR, -NR2, -NRNR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -NRSO2R, -SR, -SO2R, -SO2NR2, -S(O)R or R B Especially -NR2 or R B ;

[0054] Each R 3 It is independently halogen, -OR, -NR2, -SR, or R C Especially halogens, such as chlorine;

[0055] R B and R C Independently, the groups that are optionally substituted are selected from the following: C 1-6 Aliphatic; phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carboxylic ring or heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur; and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur.

[0056] Each R is independently hydrogen or optionally substituted with a group selected from the following: C 1-6 Aliphatic; benzyl; phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur, or:

[0057] Two R groups on the same nitrogen atom optionally together with their inserted atoms form optionally substituted 4- to 7-membered saturated rings, partially unsaturated rings, or heteroaryl rings, said ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur in addition to nitrogen; and

[0058] n is 1, 2, 3 or 4;

[0059] The prerequisite is that the compound is preferably not:

[0060]

[0061] In some embodiments, the compounds defined above (i.e., compounds of Formula I or pharmaceutically acceptable salts thereof) are not the compounds specifically disclosed in International Application No. PCT / US2021 / 49084.

[0062] In some embodiments, this disclosure provides compounds having formula I, wherein ring A is optionally substituted phenyl, preferably substituted phenyl.

[0063] In some embodiments, this disclosure provides compounds of Formula I, wherein ring A is optionally substituted HetAr. For example, in some embodiments, ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted thiophene, furanyl, pyrrole, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridinyl, pyrazinyl, indazinyl, purine, naphridinyl, pteridinyl, indolyl, isoindolyl, benzothiophene, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, terolinyl, phthalazinyl, quinazolinyl, quinoxolinyl, carbazolyl, acridineyl, phenazinyl, phenothiazinyl, and phenothiazinyl. In other such embodiments, ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted thiophene, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyridazinyl, and pyrimidinyl groups. In a preferred embodiment, ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted triazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl groups.

[0064] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is optionally substituted HetCy. For example, in some embodiments, ring A is optionally substituted HetCy, and HetCy is selected from optionally substituted tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolyl, piperazine, dioxalyl, dioxazopenyl, diazacycloheptatrienyl, oxazacycloheptatrienyl, thiaazacycloheptatrienyl, morpholinyl, quininyl, indololinyl, 3H-indolyl, chromanyl, phenanthridine, tetrahydroquinolinyl-4H-quinazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-1,4-oxazin-3(4H)-one. In other such embodiments, ring A is optionally substituted HetCy, and HetCy is selected from optionally substituted morpholino, piperazine, 2,5-dihydro-1H-pyrrole and 2,3-dihydro-1H-pyrrole.

[0065] In some embodiments, this disclosure provides compounds having formula I, wherein:

[0066] Ring A is a group that is optionally substituted with a group selected from phenyl, HetAr and HetCy;

[0067] R 2 It is R B , where R BIt is a substituted 4- to 7-membered saturated heterocycle (e.g., monocyclic or bicyclic) having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur (particularly pyrrolidine, piperidine, morpholine, and piperazine, preferably pyrrolidine), for example, substituted by 1 or 2 groups selected from: halogen, =O, =CH2, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -OH, -(CH2) 1-2 -OH, -OC 1-4 Alkyl group, -(CH2) 0-2 CO2H, -(CH2) 0-2 O(CH2) 1-5 CO2H, -(CH2) 0-2 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-2 CO2C 1-4 Alkyl group, -NH2, -(CH2) 0-2 CONH2、-(CH2) 0-2 CONR a -(CH2) 1-2 CO2H, -(CH2) 0-2 SO3H, -(CH2) 0-2 SO2NH2、-(CH2) 0-2 SO2NHC 1-4 Alkyl or -(CH2) 0-2 NR a SO2C 1-4 Alkyl, wherein R a It is either H or C each time it appears. 1-4 Alkyl; and

[0068] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0069] In other embodiments, this disclosure provides compounds of formula I, wherein:

[0070] Ring A is a group that is optionally substituted with a group selected from phenyl, HetAr and HetCy;

[0071] R 2 It is -NR2, where one R is H or a lower alkyl group (especially methyl), and the other R is a substituted C. 1-6 Aliphatic, including optionally substituted -C 1-5Alkylene-X; wherein X is selected from -OH, -OC 1-4 Alkyl, -OC 1-4 Alkylene -CO2H, -OC 1-4 Alkylene-CO2C 1-4 Alkyl group, -CO2H, -CO2C 1-4 Alkyl, -NH2, -CONH2, -CONHC 1-4 Alkyl, -CONR a -(CH2) 1-2 -OH, -CONR a -(CH2) 1-2 -COOH, -CONR a -(CH2) 1-2 -CONH2, -SO3H, -SO2NH2, -SO2NHC 1-4 Alkyl, -NR a SO2C 1-4 Alkyl groups, -P(O)(OH)2 and -OP(O)(H)(OH), wherein R a It is either H or C each time it appears. 1-4 Alkyl; and

[0072] Each R 3 Halogens, such as chlorine, including dichlorine, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0073] In some embodiments, this disclosure provides compounds of formula I, wherein:

[0074] Ring A is a group that is optionally substituted with a group selected from phenyl, HetAr and HetCy;

[0075] R 2 It is R B , where R B It is a 5- to 6-membered heteroaryl ring (particularly imidazole or pyrazole, including 1-imidazole or 4-pyrazole) optionally substituted with 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; and

[0076] Each R 3 Halogens, such as chlorine, including dichlorine, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0077] In other embodiments, this disclosure provides compounds of formula I, wherein:

[0078] Ring A is a group that is optionally substituted with a group selected from phenyl, HetAr and HetCy;

[0079] R 2 It is a substituted phenyl group (especially one or two selected from halogens, C). 1-4 Alkyl, -OH, -OC 1-4 Alkyl group, -CO2H, -CO2C 1-4 Alkyl group, -(CH2) 0-2 O(CH2) 1-5 CO2H, -(CH2) 0-2 O(CH2) 1-5 CO2C 1-4 (Substitution of alkyl, -NH2, and -CONH2 groups); and

[0080] Each R 3 Halogens, such as chlorine, including dichlorine, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0081] In other embodiments, this disclosure provides compounds of formula I, wherein:

[0082] Ring A is a group that is optionally substituted with a group selected from phenyl, HetAr and HetCy;

[0083] R 2 It is R B , where R B C is arbitrarily replaced 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic (especially -(CR2)) 1-4 NR(CR2) 0-6 CO2R); and

[0084] Each R 3 Halogens, such as chlorine, including dichlorine, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0085] In some embodiments, this disclosure provides compounds having formula I, wherein:

[0086] Ring A is a group selected from phenyl, HetAr, and HetCy that is optionally substituted; R 2 Yes -NR a R 5 ,

[0087] Each R 3 It is independently halogen, -OR, -NR2, -SR, or R C ;

[0088] Ring B1 is a phenyl, preferably a substituted phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carboxyl ring or heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0089] Ring B2 is a phenyl ring; a 4- to 7-membered saturated or partially unsaturated carbon ring or heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0090] Each R is independently hydrogen or optionally substituted with a group selected from the following: C 1-6 Aliphatic; benzyl; phenyl; a 4- to 7-membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0091] R 5 Yes - (CR2) 0-4 OR, -(CR2) 0-5 CO2R, -(CR2) 0-5 CONR2, -(CR2) 0-4 C(O)NR(CR2) 0-4 CO2R, -(CR2) 0-4 C(O)NR(CR2) 0-4 CONR2, -(CR2) 0-4 NRC(O)R, -(CR2) 0-4 SO3R, -(CR2) 0-4 SO2NR2、-(CR2) 0- 4OSO2NR2、-(CR2) 0-4 NRSO2R, -(CR2) 0-4 NRSO2OR, -(CR2) 0-4 OP(OR)2、-(CR2) 0-4 OP(O)(OR)2、-(CR2) 0-4 P(O)(OR)2、-(CR2) 0-4 OP(O)(H)OR or R B ;

[0092] Each R 6 Independently, it is a halogen, =O, =CH2, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -COR, -(CR2) 0-4 CO2R (e.g., -(CH2))0-2 CO2H or -(CH2) 0-2 CO2C 1-4 Alkyl group), -(CH2) 0-2 O(CH2) 1-5 CO2H, -(CH2) 0- 2O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-2 CONR a -(CH2) 1-2 CO2H;-(CR2) 0-4 CONR2 (e.g., -(CH2)) 0-2 CONH2), -OR (e.g., -OH or -OC) 1-4 Alkyl group), -(CR2) 1-4 OR (e.g., -(CH2)) 1-2 -OH), -NR2 (e.g., -NH2), -(CR2) 1- 4NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-4 SO3R (e.g., -(CH2)) 0- 2SO3H), -(CR2) 0-4 SO2NR2 (e.g., -(CH2)) 0-2 SO2NH2 or -(CH2) 0-2 SO2NHC 1-4 Alkyl group), -(CR2) 0- 4OSO2NR2、-(CR2) 0-4 NRSO2R (e.g., -(CH2)) 0-2 NR a SO2C 1-4 Alkyl group), -(CR2) 0-4 NRSO2OR, -(CR2) 0-4 OP(OR)2、-(CR2) 0-4 OP(O)(OR)2、-(CR2) 0-4 P(O)(OR)2、-(CR2) 0-4 OP(O)(H)OR, -B(OR)2, or R B , where R a It is either H or C each time it appears. 1-4 alkyl;

[0093] R B and R C Independently, the groups that are optionally substituted are selected from the following: C 1-6Aliphatic; phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carboxyl ring or heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur;

[0094] Each R a Independently, it is H or C 1-6 alkyl;

[0095] Each m is 0, 1, 2, 3, or 4;

[0096] n is 1, 2, 3 or 4;

[0097] q is 0, 1, or 2.

[0098] In some embodiments, ring A is an unsubstituted phenyl group. In preferred embodiments, ring A is a substituted phenyl group. In some embodiments, ring A is... In some implementations, ring A is In some implementations, ring A is In some implementations, ring A is In some implementations, ring A is In some implementations, ring A is

[0099] In some embodiments, ring A is optionally substituted HetCy, wherein HetCy is a 4- to 7-membered saturated or partially unsaturated heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is unsubstituted HetCy. In other embodiments, ring A is substituted HetCy.

[0100] In some embodiments, ring A is optionally substituted HetCy, wherein HetCy is a 4- to 7-membered saturated heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is optionally substituted. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced.

[0101] In other embodiments, ring A is optionally substituted HetCy, wherein HetCy is a 4- to 7-membered partially unsaturated heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is optionally substituted. In some implementations, ring A is optionally replaced.

[0102] In some embodiments, ring A is optionally substituted HetAr, wherein HetAr is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; wherein said 5- to 6-membered heteroaryl ring is not an imidazole or a pyrazole. In some embodiments, ring A is unsubstituted HetAr. In other embodiments, ring A is substituted HetAr. In some embodiments, ring A is optionally substituted. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced. In some implementations, ring A is optionally replaced.

[0103] In some embodiments, ring A is selected from those groups depicted in Table 1.

[0104] In some embodiments, ring A is selected from those groups depicted in Table 2.

[0105] In some implementations, R 3 The presence of R at least once is a halogen, such as chlorine or bromine. In some embodiments, R 3At least once, it appears as chlorine. In some implementations, R 3 The presence of at least once is bromine, such as at the 7th position relative to the quinoline ring. In some embodiments, n is 2 and both R 3 It is a halogen, such as two Rs. 3 It is chlorine. In some implementations, n is 2 and R 3 It refers to the chlorine at positions 7 and 8 relative to the quinoline ring. In some embodiments, n is 2 and R 3 The first occurrence of is chlorine, and R 3 Another occurrence is bromine, such as bromine at the 7-position relative to the quinoline ring and chlorine at the 8-position. In some embodiments, n is 3 and R 3 All of them are halogens, such as bromine at the 6-position relative to the quinoline ring and chlorine at the 7- and 8-positions.

[0106] In some implementations, R 3 The C that appears at least once is arbitrarily replaced. 1-6 Aliphatic, such as methyl. In some embodiments, n is 2 and R 3 One of the first appearances of is halogens, such as bromine, and R 3 Another appearance is the optional replacement of C. 1-6 Aliphatic, such as methyl. In some embodiments, n is 2 and R 3 The first occurrence of is bromine at the 7-position relative to the quinoline ring, and R 3 Another occurrence is the methyl group at the 8th position relative to the quinoline ring.

[0107] In some implementations, R 2 Yes -NR a R 5 .

[0108] In some implementations, R 5 Yes - (CR2) 2-4 OR, -(CR2) 0-5 CO2R, -(CR2) 0-5 CONR2, -(CR2) 0-4 C(O)NR(CR2) 0-4 CO2R, -(CR2) 0-4 C(O)NR(CR2) 0-4 CONR2, -(CR2) 0-4 NRC(O)R, -(CR2) 0-4 SO3R, -(CR2) 0- 4SO2NR2、-(CR2) 0-4 OSO2NR2、-(CR2) 0-4 NRSO2R, -(CR2)0-4 NRSO2OR, -(CR2) 0-4 OP(OR)2、-(CR2) 0-4 OP(O)(OR)2、-(CR2) 0-4 P(O)(OR)2 or -(CR2) 0-4 OP(O)(H)OR.

[0109] In some implementations, R 5 Yes - (CR2) 2-4 OR, -(CR2) 1-5 CO2R, -(CR2) 1-5 CONR2, -(CR2) 0-4 C(O)NR(CR2) 0-4 CO2R, -(CR2) 0-4 C(O)NR(CR2) 0-4 CONR2, -(CR2) 0-4 NRC(O)R, -(CR2) 0-4 SO3R, -(CR2) 0- 4SO2NR2、-(CR2) 0-4 OSO2NR2、-(CR2) 0-4 NRSO2R, -(CR2) 0-4 NRSO2OR, -(CR2) 0-4 OP(OR)2、-(CR2) 0-4 OP(O)(OR)2、-(CR2) 0-4 P(O)(OR)2 or -(CR2) 0-4 OP(O)(H)OR.

[0110] In some implementations, R 5 It is -(CH2) 2-4 OH, -(CH2) 2-4 O(CH2) 1-5 CO2H, -(CH2) 2-4 O(CH2) 1- 5CO2C 1-4 Alkyl group, -(CH2) 0-3 CH(CH2OH)2、-(CH2) 2-4 OC 1-4 Alkyl group, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 CONH2、-(CH2) 1-4 CONHC 1-4Alkyl group, -(CH2) 1-4 CON(C 1-4 Alkyl group 2, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 1-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2H, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 2-4 SO3H, -(CH2) 2-4 SO3C 1-4 Alkyl group, -(CH2) 2-4 SO2NH2、-(CH2) 2-4 SO2NHC 1-4 Alkyl group, -(CH2) 2-4 SO2N(C 1-4 Alkyl group 2, -(CH2) 2-4 OSO2NH2、-(CH2) 2-4 NR a SO2C 1-4 Alkyl group, -(CH2) 2- 4NR a SO3H, -(CH2) 1-4 OP(OH)2、-(CH2) 1-4 P(O)(OH)2、-(CH2) 1-4 P(O)(OH)(OC 1-4 Alkyl group or -(CH2) 2- 4OP(O)(H)OH, where R a It is either H or C each time it appears. 1-6 alkyl.

[0111] In some implementations, R 5 It is -(CH2) 2-4OH, -(CH2) 2-4 O(CH2) 1-5 CO2H, -(CH2) 2-4 O(CH2) 1- 5CO2C 1-4 Alkyl group, -(CH2) 0-3 CH(CH2OH)2、-(CH2) 1-5 CO2H, -(CH2) 1-5 CONH2、-(CH2) 1-4 C(O)NR a (CH2) 1- 4CO2H、-(CH2) 1-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2H, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 2-4 SO3H, -(CH2) 2-4 SO2NH2、-(CH2) 2-4 SO2NR a C 1-4 Alkyl group, -(CH2) 2- 4NR a SO2C 1-4 Alkyl group, -(CH2) 1-4 P(O)(OH)2 or -(CH2) 2-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl.

[0112] In some implementations, R 2 yes In some implementations, m is 1, 2, 3, or 4.

[0113] In some embodiments, ring B1 is a substituted phenyl group. In some embodiments, the phenyl group is substituted with one or more carboxyl groups.

[0114] In some implementations, ring B1 is optionally bounded by one or more R 6 A 3-carboxyphenyl group substituted with a radical.

[0115] In some implementations, ring B1 is optionally bounded by one or more R 6A 3,5-dicarboxyphenyl group substituted with a functional group.

[0116] In some embodiments, ring B1 is a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carbon ring or heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0117] In some embodiments, ring B1 is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0118] In some implementations, R 2 yes Where X is absent (i.e., is a bond in the ring), or is -CR2-, -NR-, -O-, -S-, or -SO2-; and p is 0, 1, or 2. In some embodiments, X is -CR2-, -NR-, or -O-. In some embodiments, p is 1. In some embodiments, m is 1, 2, 3, or 4.

[0119] In some implementations, each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CONH2、-(CH2) 0- 4CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1- 4CO2H、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group)1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NHC 1-4 Alkyl group, -(CH2) 0- 4NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl.

[0120] In some implementations, each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5CO2C 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH.

[0121] In some implementations, R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -(CH2) 0-2 CO2H, -(CH2) 0-2 CO2C 1-4 Alkyl group, -(CH2) 1-4 CO(N-proline), -(CH2) 0-2 C(O)NR a (CH2) 1-4 CO2H, -OH, -(CH2) 1-2 OH, -(CH2) 0-2 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-2 OC(O)C 1-4 Alkyl group, -(CH2) 0-2 SO3H, -(CH2) 0-2 SO2NH2、-(CH2) 0-2 NR a SO2C 0-2 Alkyl group, -(CH2) 0-2 OP(OH)2 or -(CR2) 0-2 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl.

[0122] In some implementations, each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, C3-6 Cycloalkyl, -(CH2) 1-4 CO2H, -(CH2) 1-4 CO(N-proline), -(CH2) 1-4 C(O)NR a (CH2) 1-4 CO2H, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 SO3H, -(CH2) 1-4 SO2NH2、-(CH2) 1-4 NR a SO2C 1-4 Alkyl group, -(CH2) 1-4 OP(OH)2 or -(CR2) 1-4 OP(O)(H)OH.

[0123] In some implementations, each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl groups, -CO2H, -CO2C 1-4 Alkyl, -CO (N-proline), -CH2CO2H, -OH, -OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -OC(O)C 1-4 Alkyl groups, -SO3H, -SO2NH2, -NR a SO2C 1-4 Alkyl, -OP(OH)2 or -OP(O)(H)OH.

[0124] In some implementations, R 2 yes In some implementations, m is 1, 2, 3, or 4. In some implementations, m is 1 or 2.

[0125] In some implementations, R 2 yes In some implementations, m is 1, 2, 3, or 4. In some implementations, m is 1 or 2.

[0126] In some implementations, each R 6 It is independently a halogen, =CH2, =O, -C 1-4 Alkyl, -C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1- 5CO2C 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2)0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0- 4SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0- 4NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-6 alkyl.

[0127] In some implementations, each R 6 It is independently a halogen, =CH2, =O, -C 1-4 Alkyl, -C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1- 5CO2C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl.

[0128] In some implementations, each R 6 It is independently a halogen, =CH2, =O, -C 1-4 Alkyl, -C 1-4 Halogenated alkyl groups, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl groups, -CO(N-proline), -CO(N-pyrrolidine-3-carboxylic acid), -C(O)NR a (CH2) 1-4 CO2H, -C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -OC) 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C1-4 Alkyl, -NR a C(O)C 1-4 Alkyl, -NR a C(O)Ph、-NR a CO(CH2) 1-4 OH, -SO3H, -SO2NH2, -NR a SO2C 1-4 Alkyl, -NR a SO2Ph, -NR a SO2(CH2) 1-4 CO2H, -OP(OH)2 or -OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl.

[0129] In some implementations, each R 6 Independently, it can be fluorine, =O, =CH2, methyl, cyclohexyl, morpholinyl, phenyl, -CF3, -OMe, -OtBu, -CO2H, or -CO2C. 1-4 Alkyl, -CO2C 1-4 Haloalkyl, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH.

[0130] In some embodiments, ring B1 is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur, wherein the carbon atom of the 5- to 6-membered heteroaryl ring is directly bonded to the carbon at the 2 position of the quinolone ring;

[0131] In some embodiments, ring B1 is an imidazole or a pyrazole. In some embodiments, the imidazole or pyrazole is unsubstituted.

[0132] In some implementations, R 2 yes In some implementations, R 2 yes

[0133] In some implementations, R 2 yes In some implementations, m is 1, 2, 3, or 4.

[0134] In some embodiments, ring B2 is a phenyl group.

[0135] In some embodiments, ring B2 is a 4- to 7-membered saturated or partially unsaturated carbon ring or heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur.

[0136] In some embodiments, ring B2 is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0137] In some implementations, R 2 yes Where X is absent (i.e., is a bond in the ring), or is -CR2-, -NR-, -O-, -S-, or -SO2-; and m is 1, 2, 3, or 4. In some embodiments, R 2 yes In some implementations, R 2 yes In some implementations, X is -CR2-, -NR-, or -O-. In some implementations, q is 1 or 2. In some implementations, q is 1. In some implementations, m is 1 or 2.

[0138] In some implementations, each R 6 It is a halogen on its own, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1- 4CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2)1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0- 4SO2NH2、-(CH2) 0-4 SO2NHC 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl.

[0139] In some implementations, each R 6 It is a halogen on its own, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl.

[0140] In some implementations, each R 6 Independently, it is halogen, -CO2H, -CO(N-proline), -C(O)NR a (CH2) 1-4 CO2H, -OH, -SO3H, -SO2NH2, -NR a SO2C 1-4 Alkyl, -OP(OH)2 or -OP(O)(H)OH, wherein R aIt is either H or C each time it appears. 1-4 alkyl.

[0141] In some implementations, R 6 Not R B .

[0142] In some implementations, m is at least 1, and at least one R 6 Including terminal -CO2H or -CO2C 1-4 Alkyl groups.

[0143] In some implementations, at least one R 6 It is -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1- 5CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2H or -(CH2) 0-4 CO2C 1-4 alkyl.

[0144] In some embodiments, this disclosure provides a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof.

[0145] In some embodiments, this disclosure provides a method for antagonizing cyclic GMP-AMP synthase (cGAS) in patients with this need, the method comprising administering an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof.

[0146] In some embodiments, this disclosure provides a method for treating inflammatory diseases, allergic diseases, or autoimmune diseases in patients in need, the method comprising administering an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof or a pharmaceutical composition thereof.

[0147] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 It is -NR2, thus forming a compound of formula Ia-1:

[0148]

[0149] Or a pharmaceutically acceptable salt thereof, wherein rings A, R, R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0150] In some embodiments, this disclosure provides compounds of formula Ia-1, wherein R 3C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0151] In some embodiments, this disclosure provides compounds of formula Ia-1, wherein ring A is an optionally substituted phenyl group, preferably a substituted phenyl group. In some embodiments, this disclosure provides compounds of formula Ia-1, wherein ring A is an optionally substituted HetCy group. In some embodiments, this disclosure provides compounds of formula Ia-1, wherein ring A is an optionally substituted HetAr group.

[0152] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 It is -NRR 5 This forms a compound of formula Ia-2:

[0153]

[0154] Or its pharmaceutically acceptable salt, wherein:

[0155] R 5 Yes - (CR2) 2-4 OR, -(CR2) 0-6 CO2R, -(CR2) 0-6 CONR2, -(CR2) 0-6 C(O)NR(CR2) 0-6 CO2R, -(CR2) 0-6 C(O)NR(CR2) 0-6 CONR2, -(CR2) 0-4 NRC(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0- 6OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or R B ;and

[0156] Rings A, R, R 3 R BEach of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0157] In some embodiments, this disclosure provides compounds of formula Ia-2, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ia-2, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ia-2, wherein ring A is optionally substituted HetAr.

[0158] In some embodiments, this disclosure provides compounds of formula Ia-2, wherein R 5 Yes - (CR2) 2-4 OR, -(CR2) 1-4 CO2R, -(CR2) 1-4 CONR2, -(CR2) 0-6 C(O)NR(CR2) 0-6 CO2R, -(CR2) 0-6 C(O)NR(CR2) 0-6 CONR2, -(CR2) 0-4 NRC(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or R B .

[0159] In some embodiments, this disclosure provides compounds of formula Ia-2, wherein R 5 Not R B .

[0160] In some embodiments, this disclosure provides compounds of formula Ia-2, wherein in -NRR 5 R in R is R a It is H or C 1-6 alkyl.

[0161] In some embodiments, this disclosure provides compounds of formula Ia-1, wherein R 3C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0162] In some embodiments, this disclosure provides compounds of formula Ia-2, wherein:

[0163] In -NRR 5 R in the formula is H or a lower alkyl group, especially methyl;

[0164] R 5 Yes - (CR2) 0-6 OR, -(CR2) 0-6 CO2R, -(CR2) 0-6 CONR2, -(CR2) 0-6 C(O)NR(CR2) 0-6 CO2R, -(CR2) 0-6 C(O)NR(CR2) 0-6 CONR2, -(CR2) 0-4 NRC(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0- 6OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2 or -(CR2) 0-6 OP(O)(H)OR; and

[0165] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0166] In certain embodiments, this disclosure provides compounds of formula Ia-2, wherein:

[0167] In -NRR 5 R in the formula is H or a lower alkyl group, especially methyl;

[0168] R 5 It is -(CH2) 2-4OH, -(CH2) 2-4 O(CH2) 1-5 CO2H, -(CH2) 2-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 3CH(CH2OH)2、-(CH2) 2-4 OC 1-4 Alkyl group, -(CH2) 1-4 CO2H, -(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 CONH2、-(CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 1-4 CON(C 1-4 Alkyl group 2, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 1-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2H, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 2-4 SO3H, -(CH2) 2-4 SO3C 1-4 Alkyl group, -(CH2) 2-4 SO2NH2、-(CH2) 2-4 SO2NHC 1-4 Alkyl group, -(CH2) 2-4 SO2N(C 1-4 Alkyl group 2, -(CH2) 2-4 OSO2NH2、-(CH2) 2-4 NR a SO2C1-4 Alkyl group, -(CH2) 2-4 NR a SO3H, -(CH2) 1-4 OP(OH)2、-(CH2) 1-4 P(O)(OH)2、-(CH2) 1-4 P(O)(OH)(OC 1-4 Alkyl group or -(CH2) 2-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 Alkyl; and

[0169] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0170] In certain embodiments, this disclosure provides compounds of formula Ia-2, wherein:

[0171] In -NRR 5 R in the formula is H or a lower alkyl group, especially methyl;

[0172] R 5 It is -(CH2) 2-4 OH, -(CH2) 0-3 CH(CH2OH)2、-(CH2) 2-4 OC 1-4 Alkyl group, -(CH2) 1-4 CO2H, -(CH2) 1- 4CO2C 1-4 Alkyl group, -(CH2) 1-4 CONH2、-(CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 1-4 CON(C 1-4 Alkyl group 2, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 1-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 1-4C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group 2, -(CH2) 2-4 SO3H, -(CH2) 2-4 SO3C 1-4 Alkyl group, -(CH2) 2- 4SO2NH2、-(CH2) 2-4 SO2NHC 1-4 Alkyl group, -(CH2) 2-4 SO2N(C 1-4 Alkyl group 2, -(CH2) 2-4 OSO2NH2、-(CH2) 2- 4NR a SO2C 1-4 Alkyl group, -(CH2) 2-4 NR a SO3H, -(CH2) 1-4 OP(OH)2、-(CH2) 1-4 P(O)(OH)2、-(CH2) 1-4 P(O)(OH)(OC 1-4 Alkyl group or -(CH2) 2-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 Alkyl; and

[0173] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0174] In other specific embodiments, this disclosure provides compounds of formula Ia-2, wherein:

[0175] In -NRR 5 R in the formula is H or a lower alkyl group, especially methyl;

[0176] R 5 It is -(CH2) 2-4 OH, -(CH2) 2-4 O(CH2) 1-5 CO2H, -(CH2) 2-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 3CH(CH2OH)2、-(CH2) 1-4CO2H, -(CH2) 1-4 CONH2、-(CH2) 1-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2H, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 2- 4SO3H, -(CH2) 2-4 SO2NH2、-(CH2) 2-4 SO2NR a C 1-4 Alkyl group, -(CH2) 2-4 NR a SO2C 1-4 Alkyl group, -(CH2) 1-4 P(O)(OH)2 or -(CH2) 2-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 Alkyl; and

[0177] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0178] In other specific embodiments, this disclosure provides compounds of formula Ia-2, wherein:

[0179] In -NRR 5 R in the formula is H or a lower alkyl group, especially methyl;

[0180] R 5 It is -(CH2) 2-4 OH, -(CH2) 0-3 CH(CH2OH)2、-(CH2) 1-4 CO2H, -(CH2) 1-4 CONH2、-(CH2) 1-4 C(O)NR a (CH2) 1-4CO2H, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 2-4 SO3H, -(CH2) 2-4 SO2NH2、-(CH2) 2-4 SO2NR a C 1-4 Alkyl group, -(CH2) 2-4 NR a SO2C 1-4 Alkyl group, -(CH2) 1-4 P(O)(OH)2 or -(CH2) 2-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 Alkyl; and

[0181] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0182] In some embodiments, for compounds of formula Ia-2 disclosed above, R 5 Includes terminal -CO2H groups. For example, in some cases, R 5 Including the terminal -(CH2) 0-4 CO2H group.

[0183] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 yes This forms a compound of formula Ia-3:

[0184]

[0185] Or its pharmaceutically acceptable salt, wherein:

[0186] Ring B1 is a phenyl, preferably a substituted phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carboxyl ring or heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur; or a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur.

[0187] Each R 6 Independently, it is halogen, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0188] m is 0, 1, 2, 3, or 4, especially 1, 2, 3, or 4; and

[0189] Rings A, R, R 3 R B Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0190] In some embodiments, this disclosure provides compounds of formula Ia-3, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ia-3, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ia-3, wherein ring A is optionally substituted HetAr.

[0191] In some embodiments, this disclosure provides compounds of formula Ia-3, wherein ring B1 is a phenyl, particularly a substituted phenyl. In other embodiments, ring B1 is not a phenyl. For example, ring B1 may be a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carboxyl ring or heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur. In some embodiments, ring B1 is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur.

[0192] In some embodiments, this disclosure provides compounds of formula Ia-3, wherein R 6 Not R B .

[0193] In some embodiments, this disclosure provides compounds of formula Ia-3, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0194] In some embodiments, for compounds of formula Ia-3 disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1- 5CO2H.

[0195] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 yes This forms a compound of formula Ia-4:

[0196]

[0197]

[0198] Or its pharmaceutically acceptable salt, wherein:

[0199] Each R 6 Independently, it is halogen, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or RB ;

[0200] m is 0, 1, 2, 3, or 4, especially 1, 2, 3, or 4; and

[0201] Rings A, R, R 3 R B Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0202] In some embodiments, this disclosure provides compounds of formula Ia-4, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ia-4, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ia-4, wherein ring A is optionally substituted HetAr.

[0203] In some embodiments, this disclosure provides compounds of formula Ia-4, wherein R 6 Not R B .

[0204] In some embodiments, this disclosure provides compounds of formula Ia-4, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0205] In some embodiments, for compounds of formula Ia-4 disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1- 5CO2H.

[0206] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 yes This forms a compound of formula Ia-5:

[0207]

[0208] Or its pharmaceutically acceptable salt, wherein:

[0209] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2).0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0210] X does not exist (i.e., it is a bond in the ring), or it is -CR2-, -NR-, -O-, -S-, or -SO2-; especially -CR2-, -NR-, -O-, -S-, or -SO2-; even more especially -CR2-, -NR-, or -O-;

[0211] m is 0, 1, 2, 3 or 4, especially 1, 2, 3 or 4;

[0212] p is 0, 1, or 2, especially 1; and

[0213] Rings A, R, R 3 R B Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0214] In some embodiments, this disclosure provides compounds of formula Ia-5, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ia-5, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ia-5, wherein ring A is optionally substituted HetAr.

[0215] In some embodiments, this disclosure provides compounds of formula Ia-5, wherein R 6 Not R B .

[0216] In some embodiments, this disclosure provides compounds of formula Ia-5, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0217] In some embodiments, this disclosure provides compounds of formula Ia-5, wherein:

[0218] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CR2, =O, -COR, -(CR2) 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0219] m is 1, 2, 3, or 4, especially 1 or 2;

[0220] p is 0 or 1, especially 1; and

[0221] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0222] In certain embodiments, this disclosure provides compounds of formula Ia-5, wherein:

[0223] Each R6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5P(O)OH2、-(CH2) 0- 4CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 0-4 NR a (CH2) 1-4CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 N[(CH2) 1-4 CO2C 1-4 [alkyl]2、-(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NHC 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0224] X is -CH2-, -NH-, or -O-;

[0225] m is 1, 2, 3, or 4, especially 1 or 2;

[0226] p is 1; and

[0227] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0228] In certain embodiments, this disclosure provides compounds of formula Ia-5, wherein each R 6 Independently, it is fluorine, -methyl, -methoxy, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2)1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0229] In certain embodiments, this disclosure provides compounds of formula Ia-5, wherein:

[0230] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NHC 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0231] X is -CH2-, -NH-, or -O-;

[0232] m is 1, 2, 3, or 4, especially 1 or 2;

[0233] p is 1; and

[0234] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0235] In other specific embodiments, this disclosure provides compounds of formula Ia-5, wherein:

[0236] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH;

[0237] X is -CH2-, -NH-, or -O-;

[0238] m is 1 or 2;

[0239] p is 1; and

[0240] Each R 3 Halogens, such as chlorine, including dichlorine, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0241] In some embodiments, for compounds of formula Ia-5 disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1- 5CO2H.

[0242] In certain embodiments, this disclosure provides compounds of formula Ia-5, wherein:

[0243] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2)1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0- 4SO2NH2、-(CH2) 0-4 SO2NHC 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0244] X is -CH2-, -NH-, or -O-;

[0245] m is 1, 2, 3, or 4, especially 1 or 2;

[0246] p is 1; and

[0247] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0248] In other specific embodiments, this disclosure provides compounds of formula Ia-5, wherein:

[0249] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH;

[0250] X is -CH2-, -NH-, or -O-;

[0251] m is 1 or 2;

[0252] p is 1; and

[0253] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0254] In some embodiments, for compounds of formula Ia-5 disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1- 5CO2H.

[0255] In certain embodiments, this disclosure provides compounds of formula Ia-5, wherein:

[0256] Each R 6It is independently a halogen, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1- 4NH2、-(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0- 4SO2NHC 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0257] X is -CH2-, -NH-, or -O-;

[0258] m is 1, 2, 3, or 4, especially 1 or 2;

[0259] p is 1; and

[0260] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0261] In other specific embodiments, this disclosure provides compounds of formula Ia-5, wherein:

[0262] Each R 6 It is a halogen on its own, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH;

[0263] X is -CH2-, -NH-, or -O-;

[0264] m is 1 or 2;

[0265] p is 1; and

[0266] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0267] In some embodiments, for compounds of formula Ia-5 disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2)0-4 O(CH2) 1- 5CO2H.

[0268] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 yes This forms a compound of formula Ia-6:

[0269]

[0270] Or its pharmaceutically acceptable salt, wherein:

[0271] Each R 6 Independently, it is a halogen, =O, =CR2, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0272] m is 0, 1, 2, 3, or 4, especially 1, 2, 3, or 4; and

[0273] Rings A, R, R 3 R B Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0274] In some embodiments, this disclosure provides compounds of formula Ia-6, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ia-6, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ia-6, wherein ring A is optionally substituted HetAr.

[0275] In some embodiments, this disclosure provides compounds of formula Ia-6, wherein R 6 Not R B .

[0276] In some embodiments, this disclosure provides compounds of formula Ia-6, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0277] In some embodiments, this disclosure provides compounds of formula Ia-6, wherein:

[0278] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CR2, =O, -COR, -(CR2) 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0279] m is 1, 2, 3, or 4, especially 1 or 2; and

[0280] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0281] In certain embodiments, this disclosure provides compounds of formula Ia-6, wherein:

[0282] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2)1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1- 5CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1- 5CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-NH2、-(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1- 4CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1- 4CO2H、-(CH2) 0-4 OP(OH)2、-(CH2) 0-4OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0283] m is 1, 2, 3, or 4, especially 1 or 2; and

[0284] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0285] In other specific embodiments, this disclosure provides compounds of formula Ia-6, wherein:

[0286] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1- 4OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0- 4SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0- 4OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0287] m is 1 or 2; and

[0288] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0289] In certain embodiments, this disclosure provides compounds of formula Ia-6, wherein:

[0290] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2)1- 4OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0- 4CO (N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0- 4CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0- 4C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1- 4CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -NH2, -(CH2) 0-4 NR a (CH2) 1- 4CO2H、-(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0- 4SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0- 4NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0291] m is 1, 2, 3, or 4, especially 1 or 2; and

[0292] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0293] In other specific embodiments, this disclosure provides compounds of formula Ia-6, wherein:

[0294] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0295] m is 1 or 2; and

[0296] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0297] In other specific embodiments, this disclosure provides compounds of formula Ia-6, wherein each R6 Independently, it can be fluorine, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0298] In certain embodiments, this disclosure provides compounds of formula Ia-6, wherein:

[0299] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0- 4CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1- 4OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0300] m is 1, 2, 3, or 4, especially 1 or 2; and

[0301] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0302] In other specific embodiments, this disclosure provides compounds of formula Ia-6, wherein:

[0303] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0304] m is 1 or 2; and

[0305] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0306] In some embodiments, this disclosure provides compounds of formula Ia-6, wherein:

[0307] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0308] m is 1, 2, 3, or 4, especially 1 or 2; and

[0309] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0310] In certain embodiments, this disclosure provides compounds of formula Ia-6, wherein:

[0311] Each R 6 It is independently a halogen, =O, -(CH2) 0-4 CO2H, -(CH2)0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NRa SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0312] m is 1, 2, 3, or 4, especially 1 or 2; and

[0313] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0314] In other specific embodiments, this disclosure provides compounds of formula Ia-6, wherein:

[0315] Each R 6 It is a halogen on its own, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0316] m is 1 or 2; and

[0317] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0318] In certain embodiments, this disclosure provides compounds of formula Ia-6, wherein m is 1;

[0319] R 6 It is -(CH2) 0-4 O(CH2) 1-5 CO2H, such as -(CH2) 1-2 O(CH2) 2-3 CO2H, including -CH2O(CH2)2CO2H; and

[0320] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0321] In some embodiments, for compounds of formula Ia-6 disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1- 5CO2H.

[0322] In certain embodiments, this disclosure provides compounds of formula Ia-6, where n is 2, R 3 It is the chlorine and R at the 7 and 8 positions relative to the quinoline ring. 6 One example is -(CH2). 0-4 O(CH2) 1-5 CO2H. In some such embodiments, the compound of formula Ia-6 is a compound of formula Ia-6*:

[0323]

[0324] Or its pharmaceutically acceptable salt, wherein:

[0325] Rings A and R 6 Each of m, individually and in combination, is as defined above and as described in the embodiments herein. In a particular embodiment, m is preferably 0.

[0326] In some embodiments, this disclosure provides compounds of formula Ia-6*, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ia-6*, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ia-6*, wherein ring A is optionally substituted HetAr.

[0327] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 yes This forms a compound of formula Ia-7:

[0328]

[0329] Or its pharmaceutically acceptable salt, wherein:

[0330] Ring B2 is a phenyl ring; a 4- to 7-membered saturated or partially unsaturated carbon ring or heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur; or a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur.

[0331] Each R 6 Independently, it is halogen, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2)0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0332] m is 0, 1, 2, 3 or 4, especially 1, 2, 3 or 4;

[0333] q is 0, 1, or 2; and

[0334] Rings A, R, R 3 R B Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0335] In some embodiments, this disclosure provides compounds of formula Ia-7, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ia-7, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ia-7, wherein ring A is optionally substituted HetAr.

[0336] In some embodiments, this disclosure provides compounds of formulas Ia-7, wherein ring B2 is a phenyl, particularly a substituted phenyl. In other embodiments, ring B2 is not a phenyl. For example, ring B2 may be a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carboxyl ring or heterocycle having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur. In some embodiments, ring B2 is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur.

[0337] In some embodiments, this disclosure provides compounds of formula Ia-7, wherein R 6 Not R B .

[0338] In some embodiments, this disclosure provides compounds of formula Ia-7, wherein in... R is R a It is H or C 1-6 alkyl.

[0339] In some embodiments, this disclosure provides compounds of formula Ia-7, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0340] In some embodiments, for compounds of formula Ia-7 disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1- 5CO2H.

[0341] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 yes This results in compounds of formula Ia-8 or formula Ia-8*, respectively:

[0342]

[0343] Or its pharmaceutically acceptable salt, wherein:

[0344] Each R 6 Independently, it is hydrogen (only on N), halogen (not on N), -COR, -(CR2). 0-6 CO2R, -(CR2) 0- 6CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0- 6NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6OP(O)(H)OR, -B(OR)2, or R B ;

[0345] X does not exist (i.e., it is a bond in the ring), or it is -CR2-, -NR-, -O-, -S- or -SO2-, especially -CR2-, -NR- or -O;

[0346] m is 1, 2, 3, or 4;

[0347] q is 0, 1, or 2; and

[0348] Rings A, R, R 3 R B Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0349] In some embodiments, this disclosure provides compounds of formula Ia-8 or Ia-8*, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ia-8 or Ia-8*, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ia-8 or Ia-8*, wherein ring A is optionally substituted HetAr.

[0350] In some embodiments, this disclosure provides compounds of formula Ia-8 or Ia-8*, wherein R 6 Not R B .

[0351] In some embodiments, this disclosure provides compounds of formula Ia-8 or formula Ia-8*, wherein in In or R in R is R a It is H or C 1-6 alkyl.

[0352] In some embodiments, this disclosure provides compounds of formula Ia-8 or Ia-8*, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0353] In some embodiments, this disclosure provides compounds of formula Ia-8 or formula Ia-8*, wherein:

[0354] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2).0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0355] m is 1, 2, 3, or 4, especially 1 or 2;

[0356] q is 1 or 2; and

[0357] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0358] In certain embodiments, this disclosure provides compounds of formula Ia-8 or formula Ia-8*, wherein:

[0359] Each R 6 It is independently a halogen, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1- 4NH2、-(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0- 4SO2NHC 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0360] m is 1, 2, 3, or 4, especially 1 or 2;

[0361] q is 1; and

[0362] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0363] In other specific embodiments, this disclosure provides compounds of formula Ia-8 or Ia-8*, wherein:

[0364] Each R 6 It is a halogen on its own, -(CH2) 0-4CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0365] m is 1 or 2;

[0366] q is 1; and

[0367] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0368] In some embodiments, for compounds of formula Ia-8 or Ia-8* disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0369] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 yes This forms a compound of formula Ia-9:

[0370]

[0371]

[0372] Or a pharmaceutically acceptable salt thereof, wherein rings A and R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0373] In some embodiments, this disclosure provides compounds of formula Ia-9, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ia-9, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ia-9, wherein ring A is optionally substituted HetAr.

[0374] In some embodiments, this disclosure provides compounds of formula Ia-9, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0375] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 yes This forms a compound of formula Ia-10:

[0376]

[0377] Or its pharmaceutically acceptable salt, wherein:

[0378] The ring C is a pyrrole group or a 4- to 10-membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocycle having 0 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur (other than nitrogen already depicted in the ring C).

[0379] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0380] m is 1, 2, 3, or 4; and

[0381] Rings A, R, R B R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0382] In some embodiments, this disclosure provides compounds of formula Ia-10, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ia-10, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ia-10, wherein ring A is optionally substituted HetAr.

[0383] In some embodiments, this disclosure provides compounds of formula Ia-10, wherein the ring C is azirrobutyl, pyrrolithyl, 2,3-dihydro-1H-pyrrolithyl, pyrrolithyl, piperidinyl, morpholinyl, thiazolyl, indololinyl, isoindolinyl, octahydroindolyl, azirroheptanyl, oxazacycloheptanane, azibicyclohexane, azibicycloheptanane, azibicyclooctane, azibicyclononane, azispiroheptane, or octahydrocyclicpentapyrrole.

[0384] In certain embodiments, this disclosure provides compounds of formula Ia-10, wherein the ring C is pyrrole, 2-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptyl or octahydrocyclopentadien[b]pyrrole.

[0385] In certain embodiments, this disclosure provides compounds of formula Ia-10, wherein the ring C is 3-hydroxyproline, 3-hydroxyproline C 1-6 Alkyl esters or 3-hydroxyproline C 1-6 Halogenated alkyl esters.

[0386] In some embodiments, this disclosure provides compounds of formula Ia-10, wherein:

[0387] Each R 6 Independently, it is fluorine, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4Alkyl, =CH2, =O, tetrazolium, imidazole acyl, thiophene, 1,2,4-oxadiazole-3(2H)-keto, morpholino, phenyl, -(CH2) 1- 4OC 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1- 4CHFCO2H、-(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2, -CH(OH)CF3, -COH(CF3)2, -(CH2)1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CHCHCO2H、-(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl groups, -OCOC 1-4 Alkyl group, -O(CH2) 1-4 CO2H, -O(CH2) 1-4 CO2C 1-4 Alkyl, -OCONR a (CH2) 0-4 CO2H, -OCONR a (CH2) 0-4 CO2C 1-4 Alkyl, -OCO-(N-morpholine), -CONH2, -CONHOH, -CONHOC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolidone-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 (piperidin-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 C(OH)(CF3)2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 CONR a SO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4(N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O-(phenyl)-(CH2) 0- 4CO2H、-(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2、-(CH2) 0- 4CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-morpholine)-(CH2) 0-4 CO2H, -CONR a (bicyclo[1.1.1]pentane)-(CH2) 0-4 CO2H, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 N[(CH2) 1-4 CO2C 1-4 [alkyl]2、-(CH2) 0-4 NR a CO(isoxazole)-OH, -(CH2)0-4 NR a SO2(benzene)-CO2H,-(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 Alkyl; and

[0388] m can be 1, 2, 3, or 4.

[0389] In certain embodiments, this disclosure provides compounds of formula Ia-10, wherein each R 6 Independently, it is fluorine, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0390] In certain embodiments, this disclosure provides compounds of formula Ia-10, wherein each R 6 Independently, it can be fluorine, -methyl, cyclohexyl, -CF3, -methoxy, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1- 5CO2H、-(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0391] In some embodiments, this disclosure provides compounds of formula Ia-10, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0392] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 yes This results in a compound of formula Ia-11:

[0393]

[0394] Or its pharmaceutically acceptable salt, wherein:

[0395] The ring C is a pyrrole group or a 4- to 10-membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocycle having 0 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur (other than nitrogen already depicted in the ring C).

[0396] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0397] m is 0, 1, 2, or 3; and

[0398] Rings A, R, R B R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0399] In some embodiments, this disclosure provides compounds of formula Ia-11, wherein ring A is optionally substituted phenyl, preferably substituted phenyl.

[0400] In some embodiments, this disclosure provides compounds of formula Ia-11, wherein ring A is optionally substituted HetCy. For example, in some embodiments, ring A is optionally substituted HetCy, and HetCy is selected from optionally substituted tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolyl, piperazine, dioxalyl, dioxazopenyl, diazacycloheptatrienyl, oxazacycloheptatrienyl, thiaazacycloheptatrienyl, morpholinyl, quininyl, indololinyl, 3H-indolyl, chromanyl, phenanthridineyl, tetrahydroquinolinyl-4H-quinazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-1,4-oxazin-3(4H)-one. In other such embodiments, ring A is optionally substituted HetCy, and HetCy is selected from optionally substituted morpholino, piperazine, 2,5-dihydro-1H-pyrrole and 2,3-dihydro-1H-pyrrole.

[0401] In some embodiments, this disclosure provides compounds of formula Ia-11, wherein ring A is optionally substituted HetAr. For example, in some embodiments, ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted thiophene, furanyl, pyrrole, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridinyl, pyrazinyl, indazinyl, purine, naphridinyl, pteridinyl, indole, isoindole, benzothiophene, benzofuranyl, dibenzofuranyl, indazole, benzimidazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, terolinyl, phthalazinyl, quinazolinyl, quinoxolinyl, carbazole, acridineyl, phenazinyl, phenothiazinyl, and phenothiazinyl. In other such embodiments, ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted thiophene, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyridazinyl, and pyrimidinyl groups. In a preferred embodiment, ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted triazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl groups.

[0402] In some embodiments, this disclosure provides compounds of formula Ia-11, wherein the ring C is azirrobutyl, pyrrolithyl, 2,3-dihydro-1H-pyrrolithyl, pyrrolithyl, piperidinyl, morpholinyl, thiazolyl, indololinyl, isoindolinyl, octahydroindolyl, azirroheptanyl, oxazacycloheptanane, azibicyclohexane, azibicycloheptanane, azibicyclooctane, azibicyclononane, azispiroheptane, or octahydrocyclopentadienylpyrrolithyl.

[0403] In certain embodiments, this disclosure provides compounds of formula Ia-11, wherein each R 6 Independently, it is fluorine, -methyl, =O, =CH2, -cyclohexyl, phenyl, morpholinyl, -OMe, -OtBu, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl or -OH; and m is 0, 1 or 2, especially 0 or 1.

[0404] In some embodiments, this disclosure provides compounds of formula Ia-11, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0405] In some embodiments, this disclosure provides compounds of formula I, wherein at least one R 3 It is a halogen, such as chlorine at the 8-position, thus forming a compound of formula Ib-1:

[0406]

[0407] Or a pharmaceutically acceptable salt thereof, wherein rings A and R 2 and R 3 Each of them individually and in combination is as defined above and as described in the embodiments herein, and n is 0, 1, 2 or 3.

[0408] In some embodiments, this disclosure provides compounds of formula Ib-1, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ib-1, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ib-1, wherein ring A is optionally substituted HetAr.

[0409] In some embodiments, this disclosure provides compounds of formula Ib-1, wherein R 2 It is R B , where R B C is arbitrarily replaced 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic compounds, such as -(CR2). 1-4 NR(CR2) 0-6 CO2R, -(CR2) 1-4 O(CR2) 0-4 CO2R, -(CR2) 1-4CO2R, -(CR2) 1-4 OH, -(CR2) 1-4 NH2、-(CR2) 1-4 C(O)NH2、-(CR2) 1-4 C(O)NHC 1-4 Alkyl or -(CR2) 1-4 C(O)N(C 1-4 Alkyl group 2, especially -(CR2) 1-4 NR(CR2) 0-4 CO2R or -(CR2) 1-4 CO2R. In some implementations, R 2 It is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a Such as -(CH2) 1-4 NR a (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 It is -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0- 4CO2R a Such as -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 Yes - (CR2) 1-4 CO2R, such as -(CR2) 1-4 CO2H, including -(CH2) 1-4 CO2H. In some implementations, R 2 Includes terminal -CO2H groups. For example, in some cases, R 2 Including the terminal -(CH2) 0-4 CO2H group.

[0410] In some embodiments, this disclosure provides compounds of formula I, where n is 2 and R 3 The chlorine at positions 7 and 8 forms a compound of formula Ib-2:

[0411]

[0412] Or a pharmaceutically acceptable salt thereof, wherein rings A and R 2 Each of them individually and in combination is as defined above and as described in the embodiments herein.

[0413] In some embodiments, this disclosure provides compounds of formula Ib-2, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ib-2, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ib-2, wherein ring A is optionally substituted HetAr.

[0414] In some embodiments, this disclosure provides compounds of formula Ib-2, wherein R 2 It is R B , where R B C is arbitrarily replaced 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic compounds, such as -(CR2). 1-4 NR(CR2) 0-6 CO2R, -(CR2) 1-4 O(CR2) 0-6 CO2R, -(CR2) 1-4 CO2R, -(CR2) 1-4 OH, -(CR2) 1-4 NH2、-(CR2) 1-4 C(O)NH2、-(CR2) 1-4 C(O)NHC 1-4 Alkyl or -(CR2) 1-4 C(O)N(C 1-4 Alkyl group 2, especially -(CR2) 1-4 NR(CR2) 0-6 CO2R or -(CR2) 1-4 CO2R. In some implementations, R 2 It is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a Such as -(CH2) 1-4 NR a (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 It is -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2)0- 4CO2R a Such as -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 Yes - (CR2) 1-4 CO2R, such as -(CR2) 1-4 CO2H, including -(CH2) 1-4 CO2H. In some implementations, R 2 Includes terminal -CO2H groups. For example, in some cases, R 2 Including the terminal -(CH2) 0-4 CO2H group.

[0415] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 yes And R 3 The chlorine at positions 7 and 8 forms a compound of formula Ic-1:

[0416]

[0417] Or its pharmaceutically acceptable salt, wherein:

[0418] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or RB ;

[0419] m is 1, 2, 3, or 4; and

[0420] Rings A, R, and R B Each of them individually and in combination is as defined above and as described in the embodiments herein.

[0421] In some embodiments, this disclosure provides compounds of formula Ic-1, wherein ring A is optionally substituted phenyl, preferably substituted phenyl.

[0422] In some embodiments, this disclosure provides compounds of formula Ic-1, wherein ring A is optionally substituted HetCy. For example, in some embodiments, ring A is optionally substituted HetCy, and HetCy is selected from optionally substituted tetrahydrofuranyl, tetrahydrothiophenyl, pyrrolyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolyl, piperazine, dioxalyl, dioxazopenyl, diazacycloheptatrienyl, oxazacycloheptatrienyl, thiaazacycloheptatrienyl, morpholinyl, quininyl, indololinyl, 3H-indolyl, chromanyl, phenanthridineyl, tetrahydroquinolinyl-4H-quinazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-1,4-oxazin-3(4H)-one. In other such embodiments, ring A is optionally substituted HetCy, and HetCy is selected from optionally substituted morpholino, piperazine, 2,5-dihydro-1H-pyrrole and 2,3-dihydro-1H-pyrrole.

[0423] In some embodiments, this disclosure provides compounds of formula Ic-1, wherein ring A is optionally substituted HetAr. For example, in some embodiments, ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted thiophene, furanyl, pyrrole, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridinyl, pyrazinyl, indazinyl, purine, naphridinyl, pteridinyl, indole, isoindole, benzothiophene, benzofuranyl, dibenzofuranyl, indazole, benzimidazolyl, benzothiazolyl, quinolinyl, isoquinolinyl, terolinyl, phthalazinyl, quinazolinyl, quinoxolinyl, carbazole, acridineyl, phenazinyl, phenothiazinyl, and phenothiazinyl. In other such embodiments, ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted thiophene, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridinyl, pyridazinyl, and pyrimidinyl groups. In a preferred embodiment, ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted triazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl groups.

[0424] In some embodiments, this disclosure provides compounds of formula Ic-1, wherein:

[0425] Each R 6 Independently, it is fluorine, -CN, methyl, =O, =CH2, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, tetrazolyl, imidazole acyl, thiophene, 1,2,4-oxadiazole-3(2H)-keto, morpholino, phenyl, -(CH2) 1- 4OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1- 4CHFCO2H、-(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2)1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2, -CH(OH)CF3, -COH(CF3)2, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CHCHCO2H、-(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl groups, -OCOC 1-4 Alkyl group, -O(CH2) 1-4 CO2H, -O(CH2) 1-4 CO2C 1-4 Alkyl, -OCONR a (CH2) 0-4 CO2H, -OCONR a (CH2) 0-4 CO2C 1-4 Alkyl, -OCO-(N-morpholine), -CONH2, -CONHOH, -CONHOC 1-4 Alkyl group, -(CH2) 0-4C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolidone-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 (piperidin-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 C(OH)(CF3)2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 CONR a SO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0- 4CO2H、-(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C1-4 Alkyl group, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2、-(CH2) 0- 4CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO-(N-piperidine)-(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-morpholine)-(CH2) 0-4 CO2H, -CONR a (bicyclo[1.1.1]pentane)-(CH2) 0-4 CO2H, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 N[(CH2) 1-4 CO2C 1-4 [alkyl]2、-(CH2) 0-4 NR a CO(isoxazole)OH, -(CH2) 0-4 NR a SO2(phenyl)-CO2H, -(CH2) 0-4 NR a SO2(CH2) 1- 4CO2H、-(CH2) 0-4 NR a SO2(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 Alkyl; and

[0426] m can be 1, 2, 3, or 4.

[0427] In certain embodiments, this disclosure provides compounds of formula Ic-1, wherein each R 6Independently, it is fluorine, =O, =CH2, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl or -OH; m is 1, 2 or 3, especially 1 or 2.

[0428] In certain embodiments, this disclosure provides compounds of formula Ic-1, wherein each R 6 Independently, it can be fluorine, =O, =CH2, -methyl, cyclohexyl, -CF3, -methoxy, -OtBu, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2 or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0429] In a particular embodiment, this disclosure provides a compound of formula Ic-1, wherein m is 1; and R 6 It is -(CH2) 0-4 O(CH2) 1-5 CO2H, such as -(CH2) 1-2 O(CH2) 2-3 CO2H, including -CH2O(CH2)2CO2H.

[0430] In some embodiments, this disclosure provides compounds of formula I, wherein R 2 It is -NRR 5 And R 3 The chlorine at positions 7 and 8 forms a compound of formula Ic-2:

[0431]

[0432] Or its pharmaceutically acceptable salt, wherein:

[0433] R 5 Yes - (CR2) 2-4 OR, -(CR2) 0-6 CO2R, -(CR2) 0-6 CONR2, -(CR2) 0-6 C(O)NR(CR2) 0-6 CO2R, -(CR2)0-6 C(O)NR(CR2) 0-6 CONR2, -(CR2) 0-6 NRCOR, -(CR2) 0-4 NR a C(O)R, -(CR2) 0-6 SO3R, -(CR2) 0- 6SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or R B ;and

[0434] Rings A, R, and R B Each of them individually and in combination is as defined above and as described in the embodiments herein.

[0435] In some embodiments, this disclosure provides compounds of formula Ic-2, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In some embodiments, this disclosure provides compounds of formula Ic-2, wherein ring A is optionally substituted HetCy. In some embodiments, this disclosure provides compounds of formula Ic-2, wherein ring A is optionally substituted HetAr.

[0436] In some embodiments, this disclosure provides compounds of formula Ic-2, wherein R 5 Not R B .

[0437] In certain embodiments, this disclosure provides compounds of formula Ic-2, wherein R 5 It is -(CH2) 2-4 OH, -(CH2) 2-4 O(CH2) 1-5 CO2H, -(CH2) 2-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-3 CH(CH2OH)2、-(CH2) 2-4 OC 1-4 Alkyl group, -(CH2) 1-4 CO2H, -(CH2)1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 CONH2、-(CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 1-4 CON(C 1-4 Alkyl group 2, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 1-4 C(O)NR a (CHMe)CO2H, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 1-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2H, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 2-4 SO3H, -(CH2) 2-4 SO3C 1-4 Alkyl group, -(CH2) 2-4 SO2NH2、-(CH2) 1-4 C(O)NR a (CH2) 2-4 SO2NH2、-(CH2) 1-4 CO(N-pyrrolidine)-SO2NH2、-(CH2) 2-4 SO2NHC 1-4 Alkyl group, -(CH2) 2-4 SO2N(C 1-4 Alkyl group 2, -(CH2) 2-4 OSO2NH2、-(CH2) 2- 4NR a (CH2) 2-4 CO2H, -(CH2) 2-4 NR a CO(CH2)2-4 CO2H, -(CH2) 2-4 NR a CO (cyclopentane)-CO2H, -(CH2) 2-4 NR a CO(benzene)-OH, -(CH2) 2-4 NR a CO(benzene)-CO2H, -(CH2) 2-4 NR a SO3H, -(CH2) 2-4 NR a SO2C 1-4 Alkyl group, -(CH2) 2- 4NR a SO2(CH2) 2-4 OH, -(CH2) 2-4 NR a SO2(CH2) 2-4 OC 1-4 Alkyl group, -(CH2) 2-4 NR a SO2(CH2) 2-4 CO2H, -(CH2) 2- 4NR a SO2(benzene)-CO2H,-(CH2) 2-4 NR a SO2 (benzene) - CO2C 1-4 Alkyl group, -(CH2) 2-4 SO2NR a (CH2) 2-4 OH, -(CH2) 2-4 (N-saccharin), -(CH2) 2-4 SO2NR a (CH2) 2-4 CO2H, -(CH2) 2-4 SO2NR a (cyclopentane)-CO2H, -(CH2) 2-4 NR a (cyclohexane)-CO2C 1-4 Alkyl group, -(CH2) 2-4 SO2(N-pyrrolidine)-CO2H, -(CH2) 2-4 SO2(N-piperidine)-CO2H, -(CH2) 1-4 OP(OH)2、-(CH2) 1-4 P(O)(OH)2、-(CH2) 1-4 P(O)(OH)(OC 1-4 Alkyl group or -(CH2) 2-4 OP(O)(H)OH, where Ra Each time it appears, it is independently H or C. 1-4 Alkyl or -SO2C 1-4 alkyl.

[0438] In some embodiments, this disclosure provides compounds of formula Ic-2, wherein in -NRR 5 R in R is R a It is H or C 1-6 Alkyl groups, especially methyl groups.

[0439] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is This forms a compound of formula Id-1:

[0440]

[0441] Or a pharmaceutically acceptable salt thereof, wherein R 2 R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0442] In some embodiments, this disclosure provides compounds of formula Id-1, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0443] In some embodiments, this disclosure provides compounds of formula Id-1, wherein R 2 It is R B , where R B C is arbitrarily replaced 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic compounds, such as -(CR2). 1-4 NR(CR2) 0-6 CO2R, -(CR2) 1-4 O(CR2) 0-6 CO2R, -(CR2) 1-4 CO2R, -(CR2) 1-4 OH, -(CR2) 1-4 NH2、-(CR2) 1-4 C(O)NH2、-(CR2) 1-4 C(O)NHC 1-4 Alkyl or -(CR2) 1-4 C(O)N(C 1-4 Alkyl group 2, especially -(CR2)1-4 NR(CR2) 0-6 CO2R or -(CR2) 1-4 CO2R. In some implementations, R 2 It is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a Such as -(CH2) 1-4 NR a (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 It is -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0- 4CO2R a Such as -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 Yes - (CR2) 1-4 CO2R, such as -(CR2) 1-4 CO2H, including -(CH2) 1-4 CO2H. In some implementations, R 2 Includes terminal -CO2H groups. For example, in some cases, R 2 Including the terminal -(CH2) 0-4 CO2H group.

[0444] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is This forms a compound of formula Id-2:

[0445]

[0446] Or a pharmaceutically acceptable salt thereof, wherein R 2 R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0447] In some embodiments, this disclosure provides compounds of formula Id-2, wherein R 3 C is independently and arbitrarily replaced. 1-6Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0448] In some embodiments, this disclosure provides compounds of formula Id-2, wherein R 2 It is R B , where R B C is arbitrarily replaced 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic compounds, such as -(CR2). 1-4 NR(CR2) 0-6 CO2R, -(CR2) 1-4 O(CR2) 0-6 CO2R, -(CR2) 1-4 CO2R, -(CR2) 1-4 OH, -(CR2) 1-4 NH2、-(CR2) 1-4 C(O)NH2、-(CR2) 1-4 C(O)NHC 1-4 Alkyl or -(CR2) 1-4 C(O)N(C 1-4 Alkyl group 2, especially -(CR2) 1-4 NR(CR2) 0-6 CO2R or -(CR2) 1-4 CO2R. In some implementations, R 2 It is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a Such as -(CH2) 1-4 NR a (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 It is -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0- 4CO2R a Such as -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 Yes - (CR2)1-4 CO2R, such as -(CR2) 1-4 CO2H, including -(CH2) 1-4 CO2H. In some implementations, R 2 Includes terminal -CO2H groups. For example, in some cases, R 2 Including the terminal -(CH2) 0-4 CO2H group.

[0449] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is This forms a compound of formula Id-3:

[0450]

[0451] Or a pharmaceutically acceptable salt thereof, wherein R 2 R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0452] In some embodiments, this disclosure provides compounds of formula Id-3, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0453] In some embodiments, this disclosure provides compounds of formula Id-3, wherein R 2 It is R B , where R B C is arbitrarily replaced 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic compounds, such as -(CR2). 1-4 NR(CR2) 0-6 CO2R, -(CR2) 1-4 O(CR2) 0-6 CO2R, -(CR2) 1-4 CO2R, -(CR2) 1-4 OH, -(CR2) 1-4 NH2、-(CR2) 1-4 C(O)NH2、-(CR2) 1-4 C(O)NHC 1-4 Alkyl or -(CR2) 1-4 C(O)N(C 1-4 Alkyl group 2, especially -(CR2) 1-4 NR(CR2) 0-6CO2R or -(CR2) 1-4 CO2R. In some implementations, R 2 It is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a Such as -(CH2) 1-4 NR a (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 It is -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0- 4CO2R a Such as -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 Yes - (CR2) 1-4 CO2R, such as -(CR2) 1-4 CO2H, including -(CH2) 1-4 CO2H. In some implementations, R 2 Includes terminal -CO2H groups. For example, in some cases, R 2 Including the terminal -(CH2) 0-4 CO2H group.

[0454] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is This results in compounds of formula Id-4 or Id-4*, respectively.

[0455]

[0456] Or a pharmaceutically acceptable salt thereof, wherein R 2 R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0457] In some embodiments, this disclosure provides compounds of formula Id-4 or formula Id-4*, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0458] In some embodiments, this disclosure provides compounds of formula Id-4 or Id-4*, wherein R 2 It is R B , where R B C is arbitrarily replaced 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic compounds, such as -(CR2). 1-4 NR(CR2) 0-6 CO2R, -(CR2) 1-4 O(CR2) 0-6 CO2R, -(CR2) 1-4 CO2R, -(CR2) 1-4 OH, -(CR2) 1-4 NH2、-(CR2) 1-4 C(O)NH2、-(CR2) 1-4 C(O)NHC 1-4 Alkyl or -(CR2) 1-4 C(O)N(C 1-4 Alkyl group 2, especially -(CR2) 1-4 NR(CR2) 0-6 CO2R or -(CR2) 1- 4CO2R. In some implementations, R 2 It is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a Such as -(CH2) 1-4 NR a (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 It is -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0-4 CO2R a Such as -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 Yes - (CR2) 1-4 CO2R, such as -(CR2)1-4 CO2H, including -(CH2) 1-4 CO2H. In some implementations, R 2 Includes terminal -CO2H groups. For example, in some cases, R 2 Including the terminal -(CH2) 0-4 CO2H group.

[0459] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is This results in compounds with the formula Id-5 or Id-5*, respectively:

[0460]

[0461] Or a pharmaceutically acceptable salt thereof, wherein R 2 R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0462] In some embodiments, this disclosure provides compounds of formula Id-5 or formula Id-5*, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0463] In some embodiments, this disclosure provides compounds of formula Id-5 or Id-5*, wherein R 2 It is R B , where R B C is arbitrarily replaced 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic compounds, such as -(CR2). 1-4 NR(CR2) 0-6 CO2R, -(CR2) 1-4 O(CR2) 0-6 CO2R, -(CR2) 1-4 CO2R, -(CR2) 1-4 OH, -(CR2) 1-4 NH2、-(CR2) 1-4 C(O)NH2、-(CR2) 1-4 C(O)NHC 1-4 Alkyl or -(CR2) 1-4 C(O)N(C 1-4 Alkyl group 2, especially -(CR2) 1-4 NR(CR2) 0-6CO2R or -(CR2) 1- 4CO2R. In some implementations, R 2 It is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a Such as -(CH2) 1-4 NR a (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 It is -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0-4 CO2R a Such as -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 Yes - (CR2) 1-4 CO2R, such as -(CR2) 1-4 CO2H, including -(CH2) 1-4 CO2H. In some implementations, R 2 Includes terminal -CO2H groups. For example, in some cases, R 2 Including the terminal -(CH2) 0-4 CO2H group.

[0464] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is And R 2 yes This forms a compound of formula Ie-1:

[0465]

[0466] Or its pharmaceutically acceptable salt, wherein:

[0467] The ring C is a pyrrole group or a 4- to 10-membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocycle having 0 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur (other than nitrogen already depicted in the ring C).

[0468] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0469] m is 1, 2, 3, or 4; and

[0470] R, R B R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0471] In some embodiments, this disclosure provides compounds of formula Ie-1, wherein the ring C is azirrobutyl, pyrrolithyl, 2,3-dihydro-1H-pyrrolithyl, pyrrolithyl, piperidinyl, morpholinyl, thiazolyl, indololinyl, isoindolinyl, octahydroindolyl, azirroheptanyl, oxazacycloheptanane, azibicyclohexane, azibicycloheptanane, azibicyclooctane, azibicyclononane, azispiroheptane, or octahydrocyclopentadienylpyrrolithyl.

[0472] In certain embodiments, this disclosure provides compounds of formula Ie-1, wherein the ring C is pyrrole, 2-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptyl or octahydrocyclopentadien[b]pyrrole.

[0473] In a particular embodiment, this disclosure provides a compound of formula Ie-1, wherein the ring C is 3-hydroxyproline, 3-hydroxyproline C 1-6 Alkyl esters or 3-hydroxyproline C 1-6 Halogenated alkyl esters.

[0474] In some embodiments, this disclosure provides compounds of formula Ie-1, wherein:

[0475] Each R 6 Independently, it is fluorine, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, =CH2, =O, tetrazolium, imidazole acyl, thiophene, 1,2,4-oxadiazole-3(2H)-keto, morpholino, phenyl, -(CH2) 1- 4OC 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1- 4CHFCO2H、-(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR aOH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2, -CH(OH)CF3, -COH(CF3)2, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CHCHCO2H、-(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl groups, -OCOC 1-4 Alkyl group, -O(CH2) 1-4 CO2H, -O(CH2) 1-4 CO2C 1-4 Alkyl, -OCONR a (CH2) 0-4 CO2H, -OCONR a (CH2) 0-4 CO2C 1-4 Alkyl, -OCO-(N-morpholine), -CONH2, -CONHOH, -CONHOC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolidone-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 (piperidin-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 C(OH)(CF3)2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 CONR a SO2C 1-4Haloalkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O-(phenyl)-(CH2) 0- 4CO2H、-(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2、-(CH2) 0- 4CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-morpholine)-(CH2) 0-4 CO2H, -CONR a (bicyclo[1.1.1]pentane)-(CH2) 0-4 CO2H, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2)1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 N[(CH2) 1-4 CO2C 1-4 [alkyl]2、-(CH2) 0-4 NR a CO(isoxazole)-OH, -(CH2) 0-4 NR a SO2(benzene)-CO2H,-(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 Alkyl; and

[0476] m can be 1, 2, 3, or 4.

[0477] In certain embodiments, this disclosure provides compounds of formula Ie-1, wherein each R 6 Independently, it is fluorine, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0478] In certain embodiments, this disclosure provides compounds of formula Ie-1, wherein each R 6 Independently, it can be fluorine, -methyl, cyclohexyl, -CF3, -methoxy, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1- 5CO2H、-(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0479] In some embodiments, this disclosure provides compounds of formula Ie-1, wherein R3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0480] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is And R 2 yes This forms a compound with the formula Ie-2:

[0481]

[0482] Or its pharmaceutically acceptable salt, wherein:

[0483] The ring C is a pyrrole group or a 4- to 10-membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocycle having 0 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur (other than nitrogen already depicted in the ring C).

[0484] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0485] m is 1, 2, 3, or 4; and

[0486] R, R B R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0487] In some embodiments, this disclosure provides compounds of formula Ie-2, wherein the ring C is azirrobutyl, pyrrolithyl, 2,3-dihydro-1H-pyrrolithyl, pyrrolithyl, piperidinyl, morpholinyl, thiazolyl, indololinyl, isoindolinyl, octahydroindolyl, azirroheptanyl, oxazacycloheptanane, azibicyclohexane, azibicycloheptanane, azibicyclooctane, azibicyclononane, azispiroheptane, or octahydrocyclopentadienylpyrrolithyl.

[0488] In certain embodiments, this disclosure provides compounds of formula Ie-2, wherein the ring C is pyrrole, 2-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptyl or octahydrocyclopentadien[b]pyrrole.

[0489] In a particular embodiment, this disclosure provides a compound of formula Ie-2, wherein the ring C is 3-hydroxyproline, 3-hydroxyproline C 1-6 Alkyl esters or 3-hydroxyproline C 1-6 Halogenated alkyl esters.

[0490] In some embodiments, this disclosure provides compounds of formula Ie-2, wherein:

[0491] Each R 6 Independently, it is fluorine, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, =CH2, =O, tetrazolium, imidazole acyl, thiophene, 1,2,4-oxadiazole-3(2H)-keto, morpholino, phenyl, -(CH2) 1- 4OC 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1- 4CHFCO2H、-(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2, -CH(OH)CF3, -COH(CF3)2, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CHCHCO2H、-(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl groups, -OCOC 1-4 Alkyl group, -O(CH2) 1-4 CO2H, -O(CH2) 1-4 CO2C 1-4 Alkyl, -OCONR a (CH2) 0-4 CO2H, -OCONR a (CH2) 0-4 CO2C 1-4 Alkyl, -OCO-(N-morpholine), -CONH2, -CONHOH, -CONHOC 1-4 Alkyl group, -(CH2)0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolidone-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 (piperidin-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 C(OH)(CF3)2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 CONR a SO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O-(phenyl)-(CH2) 0- 4CO2H、-(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2)0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2、-(CH2) 0- 4CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-morpholine)-(CH2) 0-4 CO2H, -CONR a (bicyclo[1.1.1]pentane)-(CH2) 0-4 CO2H, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 N[(CH2) 1-4 CO2C 1-4 [alkyl]2、-(CH2) 0-4 NR a CO(isoxazole)-OH, -(CH2) 0-4 NR a SO2(benzene)-CO2H,-(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 Alkyl; and

[0492] m can be 1, 2, 3, or 4.

[0493] In certain embodiments, this disclosure provides compounds of formula Ie-2, wherein each R 6 Independently, it is fluorine, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0494] In certain embodiments, this disclosure provides compounds of formula Ie-2, wherein each R 6 Independently, it can be fluorine, -methyl, cyclohexyl, -CF3, -methoxy, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1- 5CO2H、-(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0495] In some embodiments, this disclosure provides compounds of formula Ie-2, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0496] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is And R 2 yes This forms a compound of formula Ie-3:

[0497]

[0498] Or its pharmaceutically acceptable salt, wherein:

[0499] The ring C is a pyrrole group or a 4- to 10-membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocycle having 0 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur (other than nitrogen already depicted in the ring C).

[0500] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0501] m is 1, 2, 3, or 4; and

[0502] R, R B R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0503] In some embodiments, this disclosure provides compounds of formula Ie-3, wherein the ring C is azirrobutyl, pyrrolithyl, 2,3-dihydro-1H-pyrrolithyl, pyrrolithyl, piperidinyl, morpholinyl, thiazolyl, indololinyl, isoindolinyl, octahydroindolyl, azirroheptanyl, oxazacycloheptanane, azibicyclohexane, azibicycloheptanane, azibicyclooctane, azibicyclononane, azispiroheptane, or octahydrocyclopentadienylpyrrolithyl.

[0504] In certain embodiments, this disclosure provides compounds of formula Ie-3, wherein the ring C is pyrrole, 2-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptyl or octahydrocyclopentadien[b]pyrrole.

[0505] In a particular embodiment, this disclosure provides compounds of formula Ie-3, wherein the ring C is 3-hydroxyproline, 3-hydroxyproline C 1-6 Alkyl esters or 3-hydroxyproline C 1-6 Halogenated alkyl esters.

[0506] In some embodiments, this disclosure provides compounds of formula Ie-3, wherein:

[0507] Each R 6Independently, it is fluorine, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, =CH2, =O, tetrazolium, imidazole acyl, thiophene, 1,2,4-oxadiazole-3(2H)-keto, morpholino, phenyl, -(CH2) 1- 4OC 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1- 4CHFCO2H、-(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2)1-4 O(CH2) 1-5 P(O)OH2, -CH(OH)CF3, -COH(CF3)2, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CHCHCO2H、-(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl groups, -OCOC 1-4 Alkyl group, -O(CH2) 1-4 CO2H, -O(CH2) 1-4 CO2C 1-4 Alkyl, -OCONR a (CH2) 0-4 CO2H, -OCONR a (CH2) 0-4 CO2C 1-4 Alkyl, -OCO-(N-morpholine), -CONH2, -CONHOH, -CONHOC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolidone-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 (piperidin-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 C(OH)(CF3)2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 CONR a SO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2H, -(CH2) 0-4CO(N-pyrrolidine)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O-(phenyl)-(CH2) 0- 4CO2H、-(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2、-(CH2) 0- 4CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-morpholine)-(CH2) 0-4 CO2H, -CONR a (bicyclo[1.1.1]pentane)-(CH2) 0-4 CO2H, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 N[(CH2) 1-4 CO2C1-4 [alkyl]2、-(CH2) 0-4 NR a CO(isoxazole)-OH, -(CH2) 0-4 NR a SO2(benzene)-CO2H,-(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 Alkyl; and

[0508] m can be 1, 2, 3, or 4.

[0509] In certain embodiments, this disclosure provides compounds of formula Ie-3, wherein each R 6 Independently, it is fluorine, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0510] In certain embodiments, this disclosure provides compounds of formula Ie-3, wherein each R 6 Independently, it can be fluorine, -methyl, cyclohexyl, -CF3, -methoxy, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1- 5CO2H、-(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0511] In some embodiments, this disclosure provides compounds of formula Ie-3, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0512] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is And R 2 yes This results in compounds of formula Ie-4 or formula Ie-4*, respectively.

[0513]

[0514] Or its pharmaceutically acceptable salt, wherein:

[0515] The ring C is a pyrrole group or a 4- to 10-membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocycle having 0 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur (other than nitrogen already depicted in the ring C).

[0516] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0517] m is 1, 2, 3, or 4; and

[0518] R, R B R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0519] In some embodiments, this disclosure provides compounds of formula Ie-4 or Ie-4*, wherein the ring C is azirrobutyl, pyrrolithyl, 2,3-dihydro-1H-pyrrolithyl, pyrrolithyl, piperidinyl, morpholinyl, thiazolyl, indololinyl, isoindolinyl, octahydroindolyl, azirroheptanyl, oxazacycloheptanane, azibicyclohexane, azibicycloheptanane, azibicyclooctane, azibicyclononane, azispiroheptane, or octahydrocyclopentadienylpyrrolithyl.

[0520] In certain embodiments, this disclosure provides compounds of formula Ie-4 or formula Ie-4*, wherein the ring C is pyrrole, 2-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptyl or octahydrocyclopentadien[b]pyrrole.

[0521] In certain embodiments, this disclosure provides compounds of formula Ie-4 or Ie-4*, wherein the ring C is 3-hydroxyproline, 3-hydroxyproline C 1-6 Alkyl esters or 3-hydroxyproline C 1-6 Halogenated alkyl esters.

[0522] In some embodiments, this disclosure provides compounds of formula Ie-4 or formula Ie-4*, wherein:

[0523] Each R 6 Independently, it is fluorine, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, =CH2, =O, tetrazolium, imidazole acyl, thiophene, 1,2,4-oxadiazole-3(2H)-keto, morpholino, phenyl, -(CH2) 1- 4OC 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1- 4CHFCO2H、-(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2, -CH(OH)CF3, -COH(CF3)2, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CHCHCO2H、-(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl groups, -OCOC 1-4 Alkyl group, -O(CH2) 1-4 CO2H, -O(CH2) 1-4 CO2C 1-4 Alkyl, -OCONR a (CH2) 0-4 CO2H, -OCONR a (CH2) 0-4 CO2C 1-4 Alkyl, -OCO-(N-morpholine), -CONH2, -CONHOH, -CONHOC 1-4 Alkyl group, -(CH2)0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolidone-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 (piperidin-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 C(OH)(CF3)2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 CONR a SO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O-(phenyl)-(CH2) 0- 4CO2H、-(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2)0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2、-(CH2) 0- 4CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-morpholine)-(CH2) 0-4 CO2H, -CONR a (bicyclo[1.1.1]pentane)-(CH2) 0-4 CO2H, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 N[(CH2) 1-4 CO2C 1-4 [alkyl]2、-(CH2) 0-4 NR a CO(isoxazole)-OH, -(CH2) 0-4 NR a SO2(benzene)-CO2H,-(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 Alkyl; and

[0524] m can be 1, 2, 3, or 4.

[0525] In certain embodiments, this disclosure provides compounds of formula Ie-4 or Ie-4*, wherein each R 6 Independently, it is fluorine, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0526] In certain embodiments, this disclosure provides compounds of formula Ie-4 or Ie-4*, wherein each R 6 Independently, it can be fluorine, -methyl, cyclohexyl, -CF3, -methoxy, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0527] In some embodiments, this disclosure provides compounds of formula Ie-4 or Ie-4*, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0528] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is And R 2 yes This results in compounds of formula Ie-5 or formula Ie-5*, respectively.

[0529]

[0530] Or its pharmaceutically acceptable salt, wherein:

[0531] The ring C is a pyrrole group or a 4- to 10-membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocycle having 0 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur (other than nitrogen already depicted in the ring C).

[0532] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0533] m is 1, 2, 3, or 4; and

[0534] R, R B R 3 Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0535] In some embodiments, this disclosure provides compounds of formula Ie-5 or formula Ie-5*, wherein the ring C is azirrobutyl, pyrrolithyl, 2,3-dihydro-1H-pyrrolithyl, pyrrolithyl, piperidinyl, morpholinyl, thiazolyl, indololinyl, isoindolinyl, octahydroindolyl, azirroheptanyl, oxazacycloheptanane, azibicyclohexane, azibicycloheptanane, azibicyclooctane, azibicyclononane, azispiroheptane, or octahydrocyclopentadienylpyrrolithyl.

[0536] In certain embodiments, this disclosure provides compounds of formula Ie-5 or formula Ie-5*, wherein the ring C is pyrrole, 2-azabicyclo[3.1.0]hexyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptyl or octahydrocyclopentadien[b]pyrrole.

[0537] In certain embodiments, this disclosure provides compounds of formula Ie-5 or formula Ie-5*, wherein the ring C is 3-hydroxyproline, 3-hydroxyproline C 1-6 Alkyl esters or 3-hydroxyproline C 1-6 Halogenated alkyl esters.

[0538] In some embodiments, this disclosure provides compounds of formula Ie-5 or Ie-5*, wherein:

[0539] Each R 6 Independently, it is fluorine, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, =CH2, =O, tetrazolium, imidazole acyl, thiophene, 1,2,4-oxadiazole-3(2H)-keto, morpholino, phenyl, -(CH2) 1- 4OC 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1- 4CHFCO2H、-(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONRa OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2, -CH(OH)CF3, -COH(CF3)2, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CHCHCO2H、-(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl groups, -OCOC 1-4 Alkyl group, -O(CH2) 1-4 CO2H, -O(CH2) 1-4 CO2C 1-4 Alkyl, -OCONR a (CH2) 0-4 CO2H, -OCONR a (CH2) 0-4 CO2C 1-4 Alkyl, -OCO-(N-morpholine), -CONH2, -CONHOH, -CONHOC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolidone-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 (piperidin-2-one), -(CH2) 0-4 C(O)NR a (CH2) 1-4 C(OH)(CF3)2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 CONR a SO2C1-4 Haloalkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O-(phenyl)-(CH2) 0- 4CO2H、-(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2、-(CH2) 0- 4CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-morpholine)-(CH2) 0-4 CO2H, -CONR a (bicyclo[1.1.1]pentane)-(CH2) 0-4 CO2H, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NRa (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 N[(CH2) 1-4 CO2C 1-4 [alkyl]2、-(CH2) 0-4 NR a CO(isoxazole)-OH, -(CH2) 0-4 NR a SO2(benzene)-CO2H,-(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 Alkyl; and

[0540] m can be 1, 2, 3, or 4.

[0541] In certain embodiments, this disclosure provides compounds of formula Ie-5 or formula Ie-5*, wherein each R 6 Independently, it is fluorine, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Halogenated alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0542] In certain embodiments, this disclosure provides compounds of formula Ie-5 or formula Ie-5*, wherein each R 6 Independently, it can be fluorine, -methyl, cyclohexyl, -CF3, -methoxy, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0543] In some embodiments, this disclosure provides compounds of formula Ie-5 or formula Ie-5*, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0544] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is And R 2 yes This results in compounds of formula If-1:

[0545]

[0546] Or its pharmaceutically acceptable salt, wherein:

[0547] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0548] m is 0, 1, 2, 3, or 4, especially 1, 2, 3, or 4; and

[0549] R, R 3 R B Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0550] In some embodiments, this disclosure provides compounds of formula If-1, wherein R 6 Not R B .

[0551] In some embodiments, this disclosure provides compounds of formula If-1, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0552] In some embodiments, this disclosure provides compounds of formula If-1, wherein:

[0553] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CR2, =O, -COR, -(CR2) 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0554] m is 1, 2, 3, or 4, especially 1 or 2; and

[0555] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0556] In certain embodiments, this disclosure provides compounds of formula If-1, wherein:

[0557] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1- 5CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1- 5CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-NH2、-(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1- 4CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1- 4CO2H、-(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0558] m is 1, 2, 3, or 4, especially 1 or 2; and

[0559] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0560] In other specific embodiments, this disclosure provides compounds of formula If-1, wherein:

[0561] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1- 4OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0- 4SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2)0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0- 4OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0562] m is 1 or 2; and

[0563] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0564] In certain embodiments, this disclosure provides compounds of formula If-1, wherein:

[0565] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1- 4OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0- 4CO (N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0- 4CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2)0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0- 4C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1- 4CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -NH2, -(CH2) 0-4 NR a (CH2) 1- 4CO2H、-(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2)0- 4SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0- 4NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0566] m is 1, 2, 3, or 4, especially 1 or 2; and

[0567] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0568] In other specific embodiments, this disclosure provides compounds of formula If-1, wherein:

[0569] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2)0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0570] m is 1 or 2; and

[0571] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0572] In other specific embodiments, this disclosure provides compounds of formula If-1, wherein each R 6 Independently, it can be fluorine, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2)0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0573] In certain embodiments, this disclosure provides compounds of formula If-1, wherein:

[0574] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0- 4CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2)1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1- 4OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0575] m is 1, 2, 3, or 4, especially 1 or 2; and

[0576] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0577] In other specific embodiments, this disclosure provides compounds of formula If-1, wherein:

[0578] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0579] m is 1 or 2; and

[0580] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0581] In some embodiments, this disclosure provides compounds of formula If-1, wherein:

[0582] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0583] m is 1, 2, 3, or 4, especially 1 or 2; and

[0584] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0585] In certain embodiments, this disclosure provides compounds of formula If-1, wherein:

[0586] Each R 6 It is independently a halogen, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2)0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0587] m is 1, 2, 3, or 4, especially 1 or 2; and

[0588] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0589] In other specific embodiments, this disclosure provides compounds of formula If-1, wherein:

[0590] Each R 6 It is a halogen on its own, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0591] m is 1 or 2; and

[0592] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0593] In certain embodiments, this disclosure provides compounds of formula If-1, wherein m is 1;

[0594] R 6 It is -(CH2) 0-4 O(CH2) 1-5 CO2H, such as -(CH2) 1-2 O(CH2) 2-3 CO2H, including -CH2O(CH2)2CO2H; and

[0595] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0596] In some embodiments, for compounds of formula If-1 disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1- 5CO2H.

[0597] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is And R 2 yes This forms a compound with the formula If-2:

[0598]

[0599] Or its pharmaceutically acceptable salt, wherein:

[0600] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0601] m is 0, 1, 2, 3, or 4, especially 1, 2, 3, or 4; and

[0602] R, R 3 R B Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0603] In some embodiments, this disclosure provides compounds of formula If-2, wherein R 6 Not R B .

[0604] In some embodiments, this disclosure provides compounds of formula If-2, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0605] In some embodiments, this disclosure provides compounds of formula If-2, wherein:

[0606] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4Haloalkyl, =CR2, =O, -COR, -(CR2) 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0607] m is 1, 2, 3, or 4, especially 1 or 2; and

[0608] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0609] In certain embodiments, this disclosure provides compounds of formula If-2, wherein:

[0610] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2)0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2)1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1- 5CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1- 5CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-NH2、-(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1- 4CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR aC(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1- 4CO2H、-(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0611] m is 1, 2, 3, or 4, especially 1 or 2; and

[0612] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0613] In other specific embodiments, this disclosure provides compounds of formula If-2, wherein:

[0614] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4Haloalkyl, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1- 4OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0- 4SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0- 4OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0615] m is 1 or 2; and

[0616] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0617] In certain embodiments, this disclosure provides compounds of formula If-2, wherein:

[0618] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1- 4OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0- 4CO (N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0- 4CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0- 4C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1- 4CONH2、-(CH2) 0-4 C(O)NR a(CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -NH2, -(CH2) 0-4 NR a (CH2) 1- 4CO2H、-(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0- 4SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0- 4NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R aIt is either H or C each time it appears. 1-4 alkyl;

[0619] m is 1, 2, 3, or 4, especially 1 or 2; and

[0620] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0621] In certain embodiments, this disclosure provides compounds of formula If-2, wherein:

[0622] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1- 4OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2)1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0- 4CO (N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0- 4CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2)0- 4C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1- 4CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -NH2, -(CH2) 0-4 NR a (CH2) 1- 4CO2H、-(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0- 4SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2)0- 4NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0623] m is 1, 2, 3, or 4, especially 1 or 2; and

[0624] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0625] In other specific embodiments, this disclosure provides compounds of formula If-2, wherein:

[0626] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0627] m is 1 or 2; and

[0628] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0629] In other specific embodiments, this disclosure provides compounds of formula If-2, wherein each R 6 Independently, it can be fluorine, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0630] In certain embodiments, this disclosure provides compounds of formula If-2, wherein:

[0631] Each R6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0- 4CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2)0-4 NR a CO(CH2) 1- 4OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0632] m is 1, 2, 3, or 4, especially 1 or 2; and

[0633] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0634] In other specific embodiments, this disclosure provides compounds of formula If-2, wherein:

[0635] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2)0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0636] m is 1 or 2; and

[0637] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0638] In some embodiments, this disclosure provides compounds of formula If-2, wherein:

[0639] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0640] m is 1, 2, 3, or 4, especially 1 or 2; and

[0641] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0642] In certain embodiments, this disclosure provides compounds of formula If-2, wherein:

[0643] Each R 6 It is independently a halogen, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0644] m is 1, 2, 3, or 4, especially 1 or 2; and

[0645] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0646] In other specific embodiments, this disclosure provides compounds of formula If-2, wherein:

[0647] Each R 6 It is a halogen on its own, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0648] m is 1 or 2; and

[0649] Each R3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0650] In certain embodiments, this disclosure provides compounds of formula If-2, wherein m is 1;

[0651] R 6 It is -(CH2) 0-4 O(CH2) 1-5 CO2H, such as -(CH2) 1-2 O(CH2) 2-3 CO2H, including -CH2O(CH2)2CO2H; and

[0652] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0653] In some embodiments, for compounds of formula If-2 disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1- 5CO2H.

[0654] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is And R 2 yes This forms a compound with the formula If-3:

[0655]

[0656] Or its pharmaceutically acceptable salt, wherein:

[0657] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0658] m is 0, 1, 2, 3, or 4, especially 1, 2, 3, or 4; and

[0659] R, R 3 R B Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0660] In some embodiments, this disclosure provides compounds of formula If-3, wherein R 6 Not R B .

[0661] In some embodiments, this disclosure provides compounds of formula If-3, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0662] In some embodiments, this disclosure provides compounds of formula If-3, wherein:

[0663] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CR2, =O, -COR, -(CR2) 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0664] m is 1, 2, 3, or 4, especially 1 or 2; and

[0665] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0666] In certain embodiments, this disclosure provides compounds of formula If-3, wherein:

[0667] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1- 5CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1- 5CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-NH2、-(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1- 4CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1- 4CO2H、-(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0668] m is 1, 2, 3, or 4, especially 1 or 2; and

[0669] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0670] In other specific embodiments, this disclosure provides compounds of formula If-3, wherein:

[0671] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1- 4OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0- 4SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0- 4OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0672] m is 1 or 2; and

[0673] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0674] In certain embodiments, this disclosure provides compounds of formula If-3, wherein:

[0675] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1- 4OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2)1-5 P(O)OH2、-(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0- 4CO (N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0- 4CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0- 4C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1- 4CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -NH2, -(CH2) 0-4 NR a (CH2) 1- 4CO2H、-(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0- 4SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0- 4NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0676] m is 1, 2, 3, or 4, especially 1 or 2; and

[0677] Each R 3C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0678] In other specific embodiments, this disclosure provides compounds of formula If-3, wherein:

[0679] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NRa SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0680] m is 1 or 2; and

[0681] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0682] In other specific embodiments, this disclosure provides compounds of formula If-3, wherein each R 6 Independently, it can be fluorine, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0683] In certain embodiments, this disclosure provides compounds of formula If-3, wherein:

[0684] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2)0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0- 4CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1- 4OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR aSO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0685] m is 1, 2, 3, or 4, especially 1 or 2; and

[0686] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0687] In other specific embodiments, this disclosure provides compounds of formula If-3, wherein:

[0688] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2)0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0689] m is 1 or 2; and

[0690] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0691] In some embodiments, this disclosure provides compounds of formula If-3, wherein:

[0692] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0693] m is 1, 2, 3, or 4, especially 1 or 2; and

[0694] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0695] In certain embodiments, this disclosure provides compounds of formula If-3, wherein:

[0696] Each R 6 It is independently a halogen, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0697] m is 1, 2, 3, or 4, especially 1 or 2; and

[0698] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0699] In other specific embodiments, this disclosure provides compounds of formula If-3, wherein:

[0700] Each R 6 It is a halogen on its own, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0701] m is 1 or 2; and

[0702] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0703] In certain embodiments, this disclosure provides compounds of formula If-3, wherein m is 1;

[0704] R 6 It is -(CH2) 0-4 O(CH2) 1-5 CO2H, such as -(CH2) 1-2 O(CH2) 2-3 CO2H, including -CH2O(CH2)2CO2H; and

[0705] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0706] In some embodiments, for compounds of formula If-3 disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1- 5CO2H.

[0707] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is And R 2 yes This results in compounds of formula If-4 or If-4*, respectively:

[0708]

[0709] Or its pharmaceutically acceptable salt, wherein:

[0710] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0711] m is 0, 1, 2, 3, or 4, especially 1, 2, 3, or 4; and

[0712] R, R 3 R B Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0713] In some embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein R 6 Not R B .

[0714] In some embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0715] In some embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein:

[0716] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CR2, =O, -COR, -(CR2) 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0717] m is 1, 2, 3, or 4, especially 1 or 2; and

[0718] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0719] In certain embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein:

[0720] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4-O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1- 5CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1- 5CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-NH2、-(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1- 4CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1- 4CO2H、-(CH2) 0-4OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0721] m is 1, 2, 3, or 4, especially 1 or 2; and

[0722] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0723] In other specific embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein:

[0724] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1- 4OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NRa C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0- 4SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0- 4OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0725] m is 1 or 2; and

[0726] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0727] In certain embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein:

[0728] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1- 4OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0- 4CO (N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0- 4CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0- 4C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1- 4CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -NH2, -(CH2) 0-4 NR a (CH2) 1- 4CO2H、-(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2)0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0- 4SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0- 4NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0729] m is 1, 2, 3, or 4, especially 1 or 2; and

[0730] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0731] In other specific embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein:

[0732] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 0-4 O(CH2)1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0733] m is 1 or 2; and

[0734] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0735] In other specific embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein each R 6 Independently, it can be fluorine, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0736] In certain embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein:

[0737] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0- 4CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2)0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1- 4OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0738] m is 1, 2, 3, or 4, especially 1 or 2; and

[0739] Each R 3 C is independently and arbitrarily replaced. 1-6Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0740] In other specific embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein:

[0741] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0742] m is 1 or 2; and

[0743] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0744] In some embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein:

[0745] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0746] m is 1, 2, 3, or 4, especially 1 or 2; and

[0747] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0748] In certain embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein:

[0749] Each R 6 It is independently a halogen, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2)0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0750] m is 1, 2, 3, or 4, especially 1 or 2; and

[0751] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0752] In other specific embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein:

[0753] Each R 6 It is a halogen on its own, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0754] m is 1 or 2; and

[0755] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0756] In certain embodiments, this disclosure provides compounds of formula If-4 or If-4*, wherein,

[0757] m is 1;

[0758] R 6 It is -(CH2) 0-4 O(CH2) 1-5 CO2H, such as -(CH2) 1-2 O(CH2) 2-3 CO2H, including -CH2O(CH2)2CO2H; and

[0759] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0760] In some embodiments, for compounds of formula If-4 or If-4* disclosed above, m is 1 or 2, and at least one R6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0761] In some embodiments, this disclosure provides compounds of formula I, wherein ring A is And R 2 yes This results in compounds with the formula If-5 or If-5*, respectively:

[0762]

[0763] Or its pharmaceutically acceptable salt, wherein:

[0764] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR, -B(OR)2, or R B ;

[0765] m is 0, 1, 2, 3, or 4, especially 1, 2, 3, or 4; and

[0766] R, R 3 R B Each of n, individually and in combination, is as defined above and as described in the embodiments herein.

[0767] In some embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein R6 Not R B .

[0768] In some embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0769] In some embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein:

[0770] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CR2, =O, -COR, -(CR2) 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0771] m is 1, 2, 3, or 4, especially 1 or 2; and

[0772] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0773] In certain embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein:

[0774] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2)0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1- 5CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2)1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1- 5CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-NH2、-(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1- 4CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1- 4CO2H、-(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0775] m is 1, 2, 3, or 4, especially 1 or 2; and

[0776] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0777] In other specific embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein:

[0778] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0- 4CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1- 4OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0- 4SO2NH2、-(CH2) 0-4 NR a SO2C 1-4Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0- 4OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0779] m is 1 or 2; and

[0780] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0781] In certain embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein:

[0782] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl group, -(CH2) 1- 4OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl group, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 1-4 O(CH2) 1-5 CONR a 2. -(CH2) 1-4 O(CH2) 1-5 CONR a OH, -(CH2) 1-4 O(CH2) 1-5 CONR a CN, -(CH2) 1-4 O(CH2) 1-5 P(O)OH2、-(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0- 4CO (N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0- 4CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 (N-pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2)0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O (cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0- 4C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1- 4CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -NH2, -(CH2) 0-4 NR a (CH2) 1- 4CO2H、-(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl group, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C1-4 Alkyl group 2, -(CH2) 0- 4SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0- 4NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0783] m is 1, 2, 3, or 4, especially 1 or 2; and

[0784] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0785] In other specific embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein:

[0786] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a(CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 OC(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0787] m is 1 or 2; and

[0788] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0789] In other specific embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein each R 6 Independently, it can be fluorine, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, or -(CH2). 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2)0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl or -OH; and m is 1, 2 or 3, especially 1 or 2.

[0790] In certain embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein:

[0791] Each R 6 It is halogen, -C independently 1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0- 4CO2H、-(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0- 4CONH2、-(CH2) 0-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0- 4CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1- 4OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0792] m is 1, 2, 3, or 4, especially 1 or 2; and

[0793] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0794] In other specific embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein:

[0795] Each R 6 It is halogen, -C independently1-4 Alkyl, -C 1-4 Halogenated alkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0- 4CO2H、-(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl group, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0796] m is 1 or 2; and

[0797] Each R 3 C is independently and arbitrarily replaced. 1-6Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0798] In some embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein:

[0799] Each R 6 Independently, it is a halogen, =O, -COR, -(CR2). 0-6 CO2R, -(CR2) 0-6 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-6 SO3R, -(CR2) 0-6 SO2NR2、-(CR2) 0-6 OSO2NR2、-(CR2) 0-6 NRSO2R, -(CR2) 0-6 NRSO2OR, -(CR2) 0-6 OP(OR)2、-(CR2) 0-6 OP(O)(OR)2、-(CR2) 0-6 P(O)(OR)2、-(CR2) 0-6 OP(O)(H)OR or -B(OR)2;

[0800] m is 1, 2, 3, or 4, especially 1 or 2; and

[0801] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0802] In certain embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein:

[0803] Each R 6 It is independently a halogen, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl group, -(CH2) 0-4 CONH2、-(CH2) 0-4 CONHC1-4 Alkyl group, -(CH2) 0-4 CON(C 1-4 Alkyl group 2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl group (-CO2H), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2、-(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl group, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl group, -OH group, -(CH2 group) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl group, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl group 2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 SO2NR a C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2、-(CH2) 0-4 OP(OH)(OC 1-4 Alkyl group or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0804] m is 1, 2, 3, or 4, especially 1 or 2; and

[0805] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0806] In other specific embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein:

[0807] Each R 6 It is a halogen on its own, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO (N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl groups (-CO2H, -OH, -(CH2)) 1-4 OH, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl group, -(CH2) 0-4 NR a C(O)Ph、-(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2、-(CH2) 0-4 NR a SO2C 1-4 Alkyl group, -(CH2) 0-4 NRa SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a It is either H or C each time it appears. 1-4 alkyl;

[0808] m is 1 or 2; and

[0809] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0810] In certain embodiments, this disclosure provides compounds of formula If-5 or If-5*, wherein,

[0811] m is 1;

[0812] R 6 It is -(CH2) 0-4 O(CH2) 1-5 CO2H, such as -(CH2) 1-2 O(CH2) 2-3 CO2H, including -CH2O(CH2)2CO2H; and

[0813] Each R 3 C is independently and arbitrarily replaced. 1-6 Aliphatic compounds, such as methyl, or halogens, such as bromine and / or chlorine, including dichloro, including those where n is 2 and R 3 It is the chlorine at positions 7 and 8 relative to the quinoline ring.

[0814] In some embodiments, for compounds of formula If-5 or If-5* disclosed above, m is 1 or 2, and at least one R 6 Includes terminal -CO2H groups. For example, in some cases, at least one R 6 It is -(CH2) 0-4 CO2H or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0815] As defined above and described herein, each R is independently hydrogen or optionally substituted with a group selected from the following: C 1-6Aliphatic; benzyl; phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur, or two R groups on the same nitrogen atom optionally together with their intercalated atoms forming an optionally substituted 4- to 7-membered saturated ring, partially unsaturated ring, or heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur in addition to nitrogen.

[0816] In some embodiments, R is hydrogen. In some embodiments, R is C, which may be optionally substituted. 1-6 Aliphatic. In some embodiments, R is an optionally substituted benzyl group. In some embodiments, R is an optionally substituted phenyl group. In some embodiments, R is an optionally substituted 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur. In some embodiments, R is an optionally substituted 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur. In some embodiments, two R groups on the same nitrogen atom optionally form, together with their intercalated atoms, an optionally substituted 4- to 7-membered saturated ring, a partially unsaturated ring, or a heteroaryl ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur in addition to nitrogen.

[0817] In some embodiments, two R groups (e.g., -(CR2)-, etc.) on the same carbon atom optionally together with their inserted atoms form a optionally substituted 4 to 7-membered saturated or partially unsaturated ring having 0 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur.

[0818] In some embodiments, two R groups on different atoms (e.g., -P(O)(OR)2, -B(OR)2, etc.) optionally together with their inserted atoms form optional substituted 4- to 7-membered saturated or partially unsaturated rings having 0 to 3 independent heteroatoms selected from nitrogen, oxygen, phosphorus, and sulfur.

[0819] In some embodiments, R is hydrogen. In some embodiments, R is methyl. In some embodiments, R is ethyl. In some embodiments, R is isopropyl. In some embodiments, R is phenyl. In some embodiments, R is benzyl. In some embodiments, R is -(CH2). 1-5 CO2H. In some implementations, R is -(CH2). 1-5 CO2C 1-4 alkyl.

[0820] In some embodiments, R is selected from those groups depicted in Table 1.

[0821] In some embodiments, R is selected from those groups depicted in Table 2.

[0822] In some implementations, R 2 It is R B , where R B C is arbitrarily replaced 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic compounds, such as -(CR2). 1-4 NR(CR2) 0-6 CO2R, -(CR2) 1-4 O(CR2) 0-6 CO2R, -(CR2) 1-4 CO2R, -(CR2) 1-4 OH, -(CR2) 1-4 NH2、-(CR2) 1-4 C(O)NH2、-(CR2) 1-4 C(O)NHC 1-4 Alkyl or -(CR2) 1-4 C(O)N(C 1-4 Alkyl group 2, especially -(CR2) 1-4 NR(CR2) 0-6 CO2R or -(CR2) 1-4 CO2R. In some implementations, R 2 It is -(CH2) 1-4 NR a (CH2) 0- 4CO2R a Such as -(CH2) 1-4 NR a (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 It is -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0-4 CO2R a Such as -(CH2) 1-4 N(SO2C 1-4 Alkyl group (CH2) 0-4 CO2H, where R a It is either H or C each time it appears. 1-4 Alkyl group. In other embodiments, R 2 Yes - (CR2) 1-4CO2R, such as -(CR2) 1-4 CO2H, including -(CH2) 1-4 CO2H. In some implementations, R 2 Includes terminal -CO2H groups. For example, in some cases, R 2 Including the terminal -(CH2) 0-4 CO2H group.

[0823] As defined above and described in this article, R 2 It is a halogen, -OR, -NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -NRSO2R, -SR, -SO2R, -SO2NR2, -S(O)R or R B Especially -NR2 or R B ;

[0824] In some implementations, R 2 It is a halogen. In some implementations, R 2 Yes - OR. In some implementations, R 2 It is -NR2. In some implementations, R 2 It is -NRC(O)OR. In some implementations, R 2 It is -NRC(O)R. In some implementations, R 2 It is -NRC(O)NR2. In some implementations, R 2 It is -NRSO2R, -SR. In some implementations, R 2 It is -SO2R. In some implementations, R 2 It is -SO2NR2. In some implementations, R 2 It is -S(O)R. In some implementations, R 2 It is R B .

[0825] In some implementations, R 2 It is hydrogen. In some implementations, R 2 It is chlorine. In some implementations, R 2 It is methyl. In some embodiments, R 2 Yes -CF3. In some implementations, R 2 It is phenyl. In some embodiments, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes

[0826] In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In some implementations, R 2 yes In ...

Claims

1. A compound, wherein the compound has Formula I: or a pharmaceutically acceptable salt thereof, wherein: Ring A is an optionally substituted group selected from phenyl, HetAr and HetCy; HetAr is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the 5- to 6-membered heteroaryl ring is not imidazole or pyrazole; HetCy is a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur; R 2 Yes - NR a R 5 , Each R 3 are independently halogen, -OR, -NR2, -SR or R C ; Ring B1 is phenyl, preferably substituted phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carboxyl or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Ring B2 is phenyl; a 4- to 7-membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur; or a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Each R is independently hydrogen or an optionally substituted group selected from the following: C 1-6 aliphatic; benzyl; phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur; and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur, or: Two R groups on the same nitrogen optionally form, together with their intervening atoms, an optionally substituted 4 to 7 membered saturated, partially unsaturated or heteroaryl ring having, in addition to the nitrogen, 0 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur; R 5 is -(CR2) 0-4 OR, -(CR2) 0-5 CO2R, -(CR2) 0-5 CONR2, -(CR2) 0-4 C(O)NR(CR2) 0-4 CO2R, -(CR2) 0-4 C(O)NR(CR2) 0-4 CONR2, -(CR2) 0-4 NRC(O)R, -(CR2) 0-4 SO3R, -(CR2) 0-4 SO2NR2, -(CR2) 0-4 OSO2NR2, -(CR2) 0-4 NRSO2R, -(CR2) 0-4 NRSO2OR, -(CR2) 0-4 OP(OR)2, -(CR2) 0-4 OP(O)(OR)2, -(CR2) 0-4 P(O)(OR)2, -(CR2) 0-4 OP(O)(H)OR or R B ; Each R 6 are independently halogen, -COR, -(CR2) 0-4 CO2R, -(CR2) 0-4 CONR2, -OR, -(CR2) 1-4 OR, -NR2, -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-4 SO3R, -(CR2) 0- 4SO2NR2, -(CR2) 0-4 OSO2NR2, -(CR2) 0-4 NRSO2R, -(CR2) 0-4 NRSO2OR, -(CR2) 0-4 OP(OR)2, -(CR2) 0-4 OP(O)(OR)2, -(CR2) 0-4 P(O)(OR)2, -(CR2) 0-4 OP(O)(H)OR, -B(OR)2 or R B ; R B and R C is independently an optionally substituted group selected from the following: 1-6 aliphatic; phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carboxyl or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur; and a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur; Each R a independently H or C 1-6 alkyl; Each m is 0, 1, 2, 3, or 4; n is 1, 2, 3, or 4; q is 0, 1, or 2; Provided that the compound is not:

2. The compound according to claim 1, wherein ring A is optionally substituted phenyl, preferably substituted phenyl.

3. The compound of claim 1, wherein Ring A is optionally substituted HetCy.

4. The compound of claim 1, wherein Ring A is optionally substituted HetAr.

5. The compound of claim 3, wherein HetCy is a 4- to 7-membered saturated or partially unsaturated heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur.

6. The compound of claim 3, wherein HetAr is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur; wherein the 5- to 6-membered heteroaryl ring is not imidazole or pyrazole.

7. The compound of claim 1, wherein ring A is selected from 8. The compound of claim 1, wherein ring A is selected from 9. The compound of claim 1, wherein ring A is selected from 10. The compound of claim 1, wherein the compound is one of formula Id-1 to Id-5*: or a pharmaceutically acceptable salt thereof.

11. The compound of any one of claims 1 to 10, wherein R 3 At least one occurrence of is a halogen.

12. The compound of claim 11, wherein R 3 At least one occurrence of is chlorine.

13. The compound of claim 11, wherein R 3 At least one occurrence of is bromine.

14. The compound of claim 1, wherein R 3 At least one occurrence of is optionally substituted selected from C 1-6 Aliphatic group.

15. The compound of claim 11, wherein n is 2 and both R 3 It's chlorine.

16. The compound of claim 12, wherein n is 2 and R 3 are chlorine at positions 7 and 8 relative to the quinoline ring.

17. The compound of any one of claims 1 to 16, wherein R 2 Yes - NR a R 5 .

18. The compound of claim 17, wherein R 5 Yes - (CR2) 2-4 OR, -(CR2) 0-5 CO2R, -(CR2) 0-5 CONR2, -(CR2) 0-4 C(O)NR(CR2) 0-4 CO2R, -(CR2) 0-4 C(O)NR(CR2) 0-4 CONR2, -(CR2) 0-4 NRC(O)R, -(CR2) 0- 4SO3R, -(CR2) 0-4 SO2NR2, -(CR2) 0-4 OSO2NR2, -(CR2) 0-4 NRSO2R, -(CR2) 0-4 NRSO2OR, -(CR2) 0-4 OP(OR)2, -(CR2) 0-4OP(O)(OR)2, -(CR2) 0-4 P(O)(OR)2 or -(CR2) 0-4 OP(O)(H)OR.

19. The compound of claim 17, wherein R 5 Yes - (CR2) 2-4 OR, -(CR2) 1-4 CO2R, -(CR2) 1-4 CONR2, -(CR2) 0-4 C(O)NR(CR2) 0-4 CO2R, -(CR2) 0-4 C(O)NR(CR2) 0-4 CONR2, -(CR2) 0-4 NRC(O)R, -(CR2) 0- 4SO3R, -(CR2) 0-4 SO2NR2, -(CR2) 0-4 OSO2NR2, -(CR2) 0-4 NRSO2R, -(CR2) 0-4 NRSO2OR, -(CR2) 0-4 OP(OR)2, -(CR2) 0-4 OP(O)(OR)2, -(CR2) 0-4 P(O)(OR)2 or -(CR2) 0-4 OP(O)(H)OR.

20. The compound of claim 17, wherein R 5 Yes - (CH2) 2-4 OH, -(CH2) 2-4 O(CH2) 1-5 CO2H, -(CH2) 2-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-3 CH(CH2OH)2, -(CH2) 2-4 OC 1-4 Alkyl, -(CH2) 1-4 CO2H, -(CH2) 1- 4CO2C 1-4 Alkyl, -(CH2) 1-4 CONH2, -(CH2) 1-4 CONHC 1-4 Alkyl, -(CH2) 1-4 CON(C 1-4 Alkyl)2, -(CH2) 1-4 C(O)NR a(CH2) 1-4 CO2H, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CONH2, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl)2, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2H, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 2-4 SO3H, -(CH2) 2-4 SO3C 1-4 Alkyl, -(CH2) 2-4 SO2NH2, -(CH2) 2-4 SO2NHC 1-4 Alkyl, -(CH2) 2-4 SO2N(C 1-4 Alkyl)2, -(CH2) 2-4 OSO2NH2, -(CH2) 2-4 NR a SO2C 1-4 Alkyl, -(CH2) 2- 4NR a SO3H, -(CH2) 1-4 OP(OH)2, -(CH2) 1-4 P(O)(OH)2, -(CH2) 1-4 P(O)(OH)(OC 1-4 Alkyl) or -(CH2) 2- 4OP(O)(H)OH, where R a is H or C independently at each occurrence 1-6 alkyl.

21. The compound of claim 18, wherein R 5 Yes - (CH2) 2-4 OH, -(CH2) 2-4 O(CH2) 1-5 CO2H, -(CH2) 2-4 O(CH2) 1-5CO2C 1-4 Alkyl, -(CH2) 0-3 CH(CH2OH)2, -(CH2) 1-4 CO2H, -(CH2) 1-4 CONH2, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 1-4 C(O)NR a (CH2) 1-4 CONH2, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2H, -(CH2) 0-4 NR a C(O)(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 2-4 SO3H, -(CH2) 2-4 SO2NH2, -(CH2) 2-4 SO2NR a C 1-4 Alkyl, -(CH2) 2- 4NR a SO2C 1-4 Alkyl, -(CH2) 1-4 P(O)(OH)2 or -(CH2) 2-4 OP(O)(H)OH, where R a is H or C independently at each occurrence 1-4 alkyl.

22. The compound of any one of claims 1 to 16, wherein R 2 yes 23. The compound of claim 22, wherein Ring B1 is substituted phenyl.

24. The compound of claim 23, wherein the phenyl group is substituted with one or more carboxyl groups.

25. The compound of claim 23, wherein Ring B1 is optionally substituted with one or more R 6 A 3-carboxyphenyl group substituted with a group.

26. The compound of claim 23, wherein Ring B1 is optionally substituted with one or more R 6 A 3,5-dicarboxyphenyl group substituted with a group.

27. The compound of claim 22, wherein Ring B1 is a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur.

28. The compound of claim 22, wherein Ring B1 is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

29. The compound of any one of claims 22-28, wherein m is 1, 2, 3 or 4.

30. The compound of any one of claims 1-16, wherein R 2 yes in X is absent (i.e., is a bond in a ring), or is -CR2-, -NR-, -O-, -S-, or -SO2-; and p is 0, 1 or 2.

31. The compound of claim 30, wherein X is -CR2-, -NR-, or -O-.

32. The compound of claim 30 or 31, wherein p is 1.

33. The compound of any one of claims 30-32, wherein m is 1, 2, 3 or 4.

34. The compound of any one of claims 22-33, wherein each R 6 are independently halogen, =CH2, =O, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CONH2, -(CH2) 0-4 CONHC 1-4 Alkyl, -(CH2) 0-4 CON(C 1-4 Alkyl)2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2, -(CH2) 0-4 C(O)NR a (CH2) 1- 4CONHC1-4 Alkyl, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl)2, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 OC(O)C 1-4 Alkyl, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl, -(CH2) 0-4 N(C 1-4 Alkyl)2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2, -(CH2) 0-4 SO2NHC 1-4 Alkyl, -(CH2) 0-4 NR a SO2C 1-4 Alkyl, -(CH2) 0-4 OP(OH)2, -(CH2) 0-4 OP(OH)(OC 1-4 Alkyl) or -(CR2) 0-4 OP(O)(H)OH, where R a is H or C independently at each occurrence 1-4 alkyl.

35. The compound of any one of claims 22-33, wherein each R 6 are independently halogen, =CH2, =O, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -OH, -(CH2) 1-2 OH, -(CH2) 0-4OC 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 OC(O)C 1-4 Alkyl, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2, -(CH2) 0-4 NR a SO2C 1-4 Alkyl, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH.

36. The compound of any one of claims 22-33, wherein each R 6 are independently halogen, =CH2, =O, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -(CH2) 0-2 CO2H, -(CH2) 0-2 CO2C 1-4 Alkyl, -(CH2) 1-4 CO(N-proline), -(CH2) 0-2 C(O)NR a (CH2) 1-4 CO2H, -OH, -(CH2) 1-2 OH, -(CH2) 0-2 OC 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-2 OC(O)C 1-4 Alkyl, -(CH2) 0-2 SO3H, -(CH2) 0-2 SO2NH2, -(CH2) 0-2 NR a SO2C 0-2 Alkyl, -(CH2) 0-2 OP(OH)2 or -(CR2) 0-2 OP(O)(H)OH.

37. The compound of any one of claims 22-33, wherein each R 6are independently halogen, =CH2, =O, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -CO2H, -CO2C 1-4 Alkyl, -CO(N-proline), -CH2CO2H, -OH, -OC 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -OC(O)C 1-4 Alkyl, -SO3H, -SO2NH2, -NR a SO2C 1-4 Alkyl, -OP(OH)2 or -OP(O)(H)OH.

38. The compound of any one of claims 1-16, wherein R 2 yes 39. The compound of claim 38, wherein m is 1, 2, 3 or 4.

40. The compound of claim 38, wherein m is 1 or 2.

41. The compound of any one of claims 1-16, wherein R 2 yes 42. The compound of claim 41, wherein m is 1, 2, 3 or 4.

43. The compound of claim 41, wherein m is 1 or 2.

44. The compound of any one of claims 38-43, wherein each R 6 are independently halogen, =CH2, =O, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CONH2, -(CH2) 0-4 CONHC 1-4 Alkyl, -(CH2) 0-4 CON(C 1-4 Alkyl)2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO(N-pyrrolidine-3-carboxylic acid), -(CH2)0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl)-CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl)2, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1- 5CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 OC(O)C 1-4 Alkyl, -NH2, -(CH2) 1-4 NH2, -(CH2) 0- 4NHC 1-4 Alkyl, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl, -(CH2) 0-4 NR a C(O)Ph, -(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 N(C 1-4 Alkyl)2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2, -(CH2) 0-4 SO2NR a C 1-4 Alkyl, -(CH2) 0- 4NR a SO2C 1-4 Alkyl, -(CH2) 0-4 NR aSO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2, -(CH2) 0- 4OP(OH)(OC 1-4 Alkyl) or -(CR2) 0-4 OP(O)(H)OH, where R a is H or C independently at each occurrence 1-6 alkyl.

45. The compound of any one of claims 38-433, wherein each R 6 are independently halogen, =CH2, =O, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -CO2H, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO(N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NR a (CH2) 1- 4CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 Alkyl)-CO2H, -OH, -(CH2) 1-4 OH, -OC 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1- 5CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 NR a C(O)C 1-4 Alkyl, -(CH2) 0-4 NR a C(O)Ph, -(CH2) 0-4 NR a CO(CH2) 1-4 OH, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2, -(CH2) 0-4 NRa SO2C 1-4 Alkyl, -(CH2) 0- 4NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a is H or C independently at each occurrence 1-4 alkyl.

46. ​​The compound of any one of claims 38-43, wherein each R 6 are independently halogen, =CH2, =O, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Haloalkyl, -CO(N-proline), -CO(N-pyrrolidine-3-carboxylic acid), -C(O)NR a (CH2) 1-4 CO2H, -C(O)NR a -CH(C 1-4 Alkyl)-CO2H, -OH, -OC 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -NR a C(O)C 1-4 Alkyl, -NR a C(O)Ph, -NR a CO(CH2) 1-4 OH, -SO3H, -SO2NH2, -NR a SO2C 1-4 Alkyl, -NR a SO2Ph, -NR a SO2(CH2) 1-4 CO2H, -OP(OH)2 or -OP(O)(H)OH, where R a is H or C independently at each occurrence 1-4 alkyl.

47. The compound of claim 22, wherein Ring B1 is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein a carbon atom of the 5- to 6-membered heteroaryl ring is directly bonded to the carbon at the 2-position of the quinoline ring.

48. The compound of claim 28, wherein Ring B1 is imidazole or pyrazole.

49. The compound of claim 48, wherein the imidazole or pyrazole is unsubstituted.

50. The compound of claim 48, wherein R 2 yes 51. The compound of claim 48, wherein R 2 yes 52. The compound of any one of claims 1-16, wherein R 2 yes 53. The compound of claim 52, wherein Ring B2 is phenyl.

54. The compound of claim 52, wherein Ring B2 is a 4- to 7-membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur.

55. The compound of claim 52, wherein Ring B2 is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen and sulfur.

56. The compound of any one of claims 52-56, wherein m is 1, 2, 3 or 4.

57. The compound of claim 52, wherein R 2 yes in X is absent (i.e., is a bond in a ring), or is -CR2-, -NR-, -O-, -S-, or -SO2-; and m is 1, 2, 3 or 4.

58. The compound of claim 57, wherein R 2 yes 59. The compound of claim 57, wherein R 2 yes 60. The compound of any one of claims 57-59, wherein X is -CR2-, -NR-, or -O-.

61. The compound of any one of claims 57-60, wherein q is 1 or 2.

62. The compound of any one of claims 57-61, wherein q is 1.

63. The compound of any one of claims 57-62, wherein m is 1 or 2.

64. The compound of any one of claims 52-63, wherein each R 6 are independently halogen, -(CH2) 0- 4CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CONH2, -(CH2) 0-4 CONHC 1-4 Alkyl, -(CH2) 0-4 CON(C 1-4 Alkyl)2, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONH2, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CONHC 1-4 Alkyl, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 Alkyl)2, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl, -(CH2) 0-4 N(C 1-4 Alkyl)2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2, -(CH2) 0-4 SO2NHC 1-4 Alkyl, -(CH2) 0-4 NR a SO2C 1-4 Alkyl, -(CH2) 0-4 OP(OH)2, -(CH2) 0-4 OP(OH)(OC 1-4 Alkyl) or -(CR2) 0-4OP(O)(H)OH, where R a is H or C independently at each occurrence 1-4 alkyl.

65. The compound of any one of claims 52-63, wherein each R 6 are independently halogen, -(CH2) 0- 4CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 C(O)NR a (CH2) 1-4 CO2H, -OH, -(CH2) 1-4 OH, -(CH2) 0- 4SO3H, -(CH2) 0-4 SO2NH2, -(CH2) 0-4 NR a SO2C 1-4 Alkyl, -(CH2) 0-4 OP(OH)2 or -(CR2) 0-4 OP(O)(H)OH, where R a is H or C independently at each occurrence 1-4 alkyl.

66. The compound of any one of claims 52-63, wherein each R 6 are independently halogen, -CO2H, -CO(N-proline), -C(O)NR a (CH2) 1-4 CO2H, -OH, -SO3H, -SO2NH2, -NR a SO2C 1-4 Alkyl, -OP(OH)2 or -OP(O)(H)OH, where R a is H or C independently at each occurrence 1-4 alkyl.

67. The compound of any one of claims 1-66, wherein R 6 Not R B .

68. The compound of any one of claims 1-67, wherein m is at least 1, and at least one R 6 Including terminal -CO2H or -CO2C 1-4 Alkyl group.

69. The compound of claim 68, wherein at least one R 6 Yes - (CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2)1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 CO2H or -(CH2) 0-4 CO2C 1-4 alkyl.

70. The compound of claim 68, wherein at least one R 6 yes 71. A compound, wherein the compound is selected from: or a pharmaceutically acceptable salt thereof.

72. A compound, wherein the compound is selected from: or a pharmaceutically acceptable salt thereof.

73. A pharmaceutical composition comprising a compound according to any one of claims 1-72.

74. A method of antagonizing cyclic GMP-AMP synthase (cGAS) in a patient in need thereof, the method comprising administering an effective amount of a compound of any one of claims 1-72 or a pharmaceutical composition of claim 73.

75. A method of treating an inflammatory disease, an allergic disease, an autoimmune disease, a cardiovascular disease, or a neurodegenerative disease in a patient in need thereof, the method comprising administering an effective amount of a compound of any one of claims 1-72 or a pharmaceutical composition of claim 73.

76. Use of a compound according to any one of claims 1 to 72 or a pharmaceutical composition according to claim 73 in the preparation of a medicament for antagonizing cyclic GMP-AMP synthase (cGAS) in a patient in need thereof.

77. Use of a compound according to any one of claims 1 to 72 or a pharmaceutical composition according to claim 73 in the preparation of a medicament for treating an inflammatory disease, an allergic disease, an autoimmune disease, a cardiovascular disease or a neurodegenerative disease in a patient in need thereof.

78. A compound according to any one of claims 1-72 for use in therapy, such as for treating an inflammatory disease, an allergic disease, an autoimmune disease, a cardiovascular disease or a neurodegenerative disease in a patient, and / or for antagonizing cyclic GMP-AMP synthase (cGAS) in a patient.

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