Quinoline cGas antagonist compounds

Abstract

The present disclosure provides compounds that are cGAS antagonists, methods for preparing the compounds, pharmaceutical compositions containing the compounds, and their uses in medical therapy.

Description

[Background technology]

[0001] 1. Background Cyclic GMP-AMP synthase (cGAS) (UniProtKB-Q8N884) is an enzyme that acts as a DNA sensor to trigger immune responses against pathogens through activation of the stimulator of interferon genes (STING) receptor. Aberrant activation of cGAS by self-DNA has been shown to underlie debilitating and sometimes fatal autoimmune diseases. Knockout studies in animal models have demonstrated that cGAS inhibition is a promising approach for therapeutic intervention. Furthermore, recent studies have shown that the cGAS-STING pathway plays an important 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 is a continuing need in the art for effective treatments for human 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. Thus, there remains a need to discover potent and selective small molecule inhibitors of cGAS that are useful for treating these and other debilitating human diseases associated with aberrant activation of cGAS. Summary of the Invention

[0003] 2. Overview The present disclosure relates to small molecule cGAS antagonist compounds, methods for preparing the compounds, pharmaceutical compositions containing the compounds, and their use in medical therapy. In particular, the present disclosure provides quinoline cGAS antagonist compounds that are useful as cGAS inhibitors. An advantage of the compounds provided herein is that they are capable of a wide range of pharmacological activity consistent with cGAS inhibition. In addition, the present disclosure provides methods of using the compounds described herein for the treatment of inflammatory diseases, allergic diseases, autoimmune diseases, and infectious diseases. The compounds can also be used to treat aging-related or age-related diseases, such as neurodegenerative diseases, cardiovascular diseases, liver diseases, and kidney diseases, cancer, and premature aging.

[0004] It has now been found that compounds of the present disclosure, and pharmaceutically acceptable compositions thereof, are effective in inhibiting cGAS. Such compounds of the present disclosure have the general formula I: [ka] or a pharmaceutically acceptable salt thereof, wherein each variable is as defined and described herein.

[0005] The disclosed compounds and pharmaceutically acceptable compositions thereof are useful for treating a variety of diseases, disorders, or conditions associated with the abnormal activation of cGAS, including those described herein.

[0006] The compounds provided by the present disclosure are also useful for studying the cGAS enzyme in vitro or in vivo for biological and pathological phenomena, as well as for the comparative evaluation of new cGAS antagonists or other regulators of cGAS, signaling pathways, and cytokine levels. DETAILED DESCRIPTION OF THE INVENTION

[0007] 3. Detailed Description 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 may 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 requires otherwise, throughout the specification and the following claims, the word "comprise" and variations thereof, such as "comprises" and "comprising," should be interpreted in an open and inclusive sense, i.e., "including, but not limited to." Furthermore, the headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed invention. References throughout this specification to "one embodiment" or "an embodiment" mean that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least one embodiment. Thus, appearances of the phrase "in one embodiment" or "in an embodiment" in various places throughout this specification do not necessarily all refer to the same embodiment. Furthermore, particular features, structures, or characteristics may be combined in any suitable manner in one or more embodiments. Also, as used in this specification and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the content clearly dictates otherwise. Note that the term "or" is also generally used in its sense, including "and / or," unless the content clearly dictates otherwise.

[0008] 3.1.Definition Compounds of the present disclosure include those generally described herein, and are further exemplified by the classes, subclasses, and species disclosed herein. As used herein, the following definitions shall apply unless otherwise specified. For purposes of this disclosure, chemical elements are defined as defined in the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75 th Further, 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, the entire contents of which are incorporated herein by reference. th Ed., Ed.: Smith, M. B. and March, J., John Wiley & Sons, New York: 2001.

[0009] As used herein, the term "aliphatic" or "aliphatic group" means a straight-chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is fully saturated or contains one or more units of unsaturation, or a monocyclic or bicyclic hydrocarbon that is fully saturated or contains one or more units of unsaturation but is not aromatic (also referred to herein as "carbocycle," "alicyclic," or "cycloalkyl") and has a single point of attachment to the rest of the molecule. Unless otherwise specified, an aliphatic group contains 1-6 aliphatic carbon atoms. In some embodiments, an aliphatic group contains 1-5 aliphatic carbon atoms. In other embodiments, an aliphatic group contains 1-4 aliphatic carbon atoms. In still other embodiments, an aliphatic group contains 1-3 aliphatic carbon atoms, and in still other embodiments, an aliphatic group contains 1-2 aliphatic carbon atoms. In some embodiments, "alicyclic" (or "carbocycle" or "cycloalkyl") refers to a monocyclic C3-C6 hydrocarbon that is fully saturated or contains one or more units of unsaturation, but is not aromatic, and has a single point of attachment to the rest of the molecule. Suitable aliphatic groups include, but are not limited to, straight-chain or branched, substituted or unsubstituted alkyl groups, alkenyl groups, alkynyl groups, and hybrids thereof, such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl, or (cycloalkyl)alkenyl.

[0010] As used herein, the term "bridged bicyclic" refers to any bicyclic ring 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 of atoms, or an atomic or valence bond connecting two bridgeheads, and a "bridgehead" is any skeletal atom of a ring system that is bonded to three or more skeletal atoms (excluding hydrogen). In some embodiments, a 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 the groups described below, in which each group is attached to the remainder of the molecule at any substitutable carbon or nitrogen atom. Unless otherwise specified, a bridged bicyclic group may be substituted with one or more substituents, such as those described for aliphatic groups. Additionally or alternatively, any substitutable nitrogen of a bridged bicyclic group may be substituted. Exemplary bridged bicyclic compounds include: [ka] In some embodiments, the bicyclo[1.1.1.]pentane is a phenyl isostere.

[0011] The term "lower alkyl" refers to a C 1-4 It refers to a straight-chain or branched alkyl group. Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0012] The term "lower haloalkyl" refers to a C alkyl group substituted by one or more halogen atoms. 1-4 Refers to a straight or branched chain alkyl group.

[0013] The term "heteroatom" refers to 、 containing nitrogen, sulfur, phosphorus, or silicon in any oxidized form; any basic nitrogen in quaternized form; or an oxygen, sulfur, nitrogen, phosphorus, or silicon atom in a heterocyclic ring Oxygen, sulfur, nitrogen, phosphorus or silicon means one or more of the following:

[0014] As used herein, the term "unsaturated" means that a moiety has one or more units of unsaturation.

[0015] As used herein, the term "divalent C 1-8 (or C 1-6 ) saturated or unsaturated, straight or branched hydrocarbon chain" refers to divalent alkylene, alkenylene, and alkynylene chains that are straight or branched as defined herein.

[0016] The term "alkylene" refers to a divalent alkyl group. An "alkylene chain" is a polymethylene group, i.e., -(CH) n - (wherein n is a positive integer, preferably 1 to 6, 1 to 4, 1 to 3, 1 to 2, or 2 to 3). A substituted alkylene chain is a polymethylene group in which one or more methylene hydrogen atoms have been replaced by a substituent. Suitable substituents include those described below for substituted aliphatic groups.

[0017] The term "alkenylene" refers to a divalent alkenyl group. A substituted alkenylene chain is a polymethylene group containing at least one double bond in which one or more hydrogen atoms are replaced by a substituent. Suitable substituents include those described below for substituted aliphatic groups.

[0018] As used herein, the term "cyclopropylenyl" refers to a divalent cyclopropyl group of the following structure: [ka]

[0019] The term "halogen" means F, Cl, Br or I.

[0020] The term "aryl," used alone or as part of a larger moiety such as "aralkyl," "aralkoxy," or "aryloxyalkyl," refers to a monocyclic or bicyclic ring system having a total of 4 to 14 ring members, in which at least one ring in the system is aromatic and each ring in the system contains 3 to 7 ring members. The term "aryl" may be used interchangeably with the term "aryl ring." In certain embodiments of the present disclosure, "aryl" refers to an aromatic ring system, including, but not limited to, phenyl, biphenyl, naphthyl, anthracyl, and the like, which may bear one or more substituents. Groups in which an aromatic ring is fused to one or more non-aromatic rings, such as indanyl, phthalimidyl, naphthymidyl, phenanthridinyl, or tetrahydronaphthyl, are also included within the scope of the term "aryl" as used herein.

[0021] The terms "heteroaryl" and "heteroar-," used alone or as part of a larger moiety, such as "heteroaralkyl" or "heteroaralkoxy," refer to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms, sharing 6, 10, or 14 pi electrons in the cyclic array, and having 1 to 5 heteroatoms in addition to carbon atoms. In reference to "heteroaryl," the term "heteroatom" specifically includes, but is not limited to, nitrogen, oxygen, or sulfur, including any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. Heteroaryl groups include, but are not limited to, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl. As used herein, the terms "heteroaryl" and "heteroar-" also include groups in which a heteroaromatic ring is fused to one or more aryl, alicyclic, or heterocyclyl rings, and the radical or point of attachment is on the heteroaromatic ring. Non-limiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, 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 contain one or more oxo (=O) or thioxo (=S) substituents. The term "heteroaryl" may be used interchangeably with the terms "heteroaryl ring," "heteroaryl group," or "heteroaromatic," any of which terms include rings that are optionally substituted. The term "heteroaralkyl" refers to an alkyl group substituted by a heteroaryl, where the alkyl and heteroaryl portions are optionally substituted independently.

[0022] As used herein, the terms "heterocycle," "heterocyclyl," "heterocyclic radical," and "heterocyclic ring" are used interchangeably and refer to a stable 5- to 7-membered monocyclic or 7- to 10-membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated and has, in addition to carbon atoms, one or more, preferably one to four, heteroatoms as defined above. When used in reference to a ring atom of a heterocycle, the term "nitrogen" includes substituted nitrogen. As an example, a saturated or partially unsaturated ring can have zero to three heteroatoms selected from oxygen, sulfur, or nitrogen.

[0023] The heterocyclic ring can be attached to a provided compound at any heteroatom or carbon atom that results in a stable structure, and any of the ring atoms can be substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, but are not limited to, tetrahydrofuranyl, tetrahydrothiophenyl, tetrahydrofuranyl ... 、 Examples include pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. The terms "heterocycle," "heterocyclyl," "heterocyclyl ring," "heterocyclic group," "heterocyclic moiety," and "heterocyclic radical" are used interchangeably herein and also include groups in which a heterocyclyl ring is fused to one or more aryl rings, heteroaryl rings, or alicyclic rings, such as indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl. Heterocyclyl groups can be monocyclic, bicyclic, bridged bicyclic, or spirocyclic. The heterocyclic ring may contain one or more oxo (=O) or thioxo (=S) substituents. The term "heterocyclylalkyl" refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions are optionally independently substituted.

[0024] As used herein, the term "partially unsaturated" refers to a ring moiety that contains at least one double or triple bond. The term "partially unsaturated" is intended to encompass rings with multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties as defined herein.

[0025] As described herein, the compounds of the present disclosure may contain "substituted" moieties. Generally, the term "substituted" means that one or more hydrogen atoms of the specified moiety have been replaced by a suitable substituent. Unless otherwise specified, an "optionally substituted" group may have a suitable substituent at one or more substitutable positions of the group, and when multiple positions in any given structure are substituted with multiple substituents selected from a specified group, the substituents may be the same or different at every position. The combinations of substituents envisioned by the present disclosure preferably result in the formation of stable or chemically feasible compounds. As used herein, the term "stable" refers to compounds that do not change substantially when subjected to conditions that allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein.

[0026] Suitable monovalent substituents on a substitutable carbon atom of an "optionally substituted" group are independently halogen; -(CH) 0-6 R°;-(CH2) 0-6 OR°;-O(CH2) 0-6 R o ;-O-(CH2) 0-6 C(O)OR°;-(CH2) 0-6 CH(OR°)2;-(CH2) 0-6 SR°;-(CH2) 0-6 Ph (wherein Ph may be substituted by R°); —(CH2) 0-6 O(CH2) 0-1 Ph (wherein Ph may be substituted by R°); -CH=CHPh (wherein Ph may be substituted by R°); -(CH) 0-6 O(CH2) 0-1-pyridyl (which may be substituted by R°); -NO2; -CN; -N3; ​​-(CH2) 0-6 N(R°)2;-(CH2) 0-6 N(R°)C(O)R°;-N(R°)C(S)R°;-(CH2) 0-6 N(R°)C(O)NR°2;-N(R°)C(S)NR°2;-(CH2) 0-6 N(R°)C(O)OR°;-N(R°)N(R°)C(O)R°;-N(R°)N(R°)C(O)NR°2;-N(R°)N(R°)C(O)OR°;-(CH2) 0-6 C(O)R°;-C(S)R°;-(CH2) 0-6 C(O)OR°;-(CH2) 0-6 C(O)SR°;-(CH2) 0-6 C(O)OSiR°3;-(CH2) 0-6 OC(O)R°;-OC(O)(CH2) 0-6 SR°,-(CH2) 0-6 SC(O)R°;-(CH2) 0-6 C(O)NR°2;-C(S)NR°2;-C(S)SR°;-SC(S)SR°,-(CH2) 0-6 OC(O)NR°2;-C(O)N(OR°)R°;-C(O)C(O)R°;-C(O)CH2C(O)R°;-C(NOR°)R°;-(CH2) 0-6 SSR°;-(CH2) 0-6 S(O)2R°;-(CH2) 0-6 S(O)2OR°;-(CH2) 0-6 OS(O)2R°;-S(O)2NR°2;-(CH2) 0-6 S(O)R°;-N(R°)S(O)2NR°2;-N(R°)S(O)2R°;-N(OR°)R°;-C(NH)NR°2;-P(O)2R°; -P(O)R°2;-P(O)(OR°)2;-OP(O)(R°)OR°;-OP(O)R°2;-OP(O)(OR°)2;SiR°3;-(C 1-4 linear or branched alkylene)ON(R°)2; or -(C 1-4 linear or branched alkylene)C(O)ON(R°)2, where each R° is optionally substituted as defined below and independently represents hydrogen, C 1-6Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, -CH2- (a 5- to 6-membered heteroaryl ring), or a 5- to 6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; or, notwithstanding the above definitions, two independent occurrences of R° taken together with their intervening atoms form a 3- to 12-membered saturated, partially unsaturated, or aryl monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.

[0027] Suitable monovalent substituents on R° (or the ring formed by taking two independent occurrences of R° together with their intervening atoms) are independently halogen, —(CH) 0-2 R ● ,-(Halo R ● ), -(CH2) 0-2 OH, -(CH2) 0-2 OR ● , -(CH2) 0-2 CH(OR ● )2, -O(HaloR ● ), -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 Linear or branched alkylene)C(O)OR ● , or -SSR ● where each R ●is unsubstituted or, if preceded by "halo", is substituted only by one or more halogens, and C 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 or a 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R° include =0 and =S.

[0028] Suitable divalent substituents on a saturated carbon atom of an "optionally substituted" group include: ═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-(wherein, R * Each independent occurrence of is hydrogen, optionally substituted as defined below. 1-6 (Selected from aliphatic or unsubstituted 5-6 membered saturated, partially unsaturated, or aryl rings having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.) Suitable divalent substituents attached to adjacent substitutable carbon atoms of an "optionally substituted" group include -O(CR * 2) 2-3 O— (wherein R * Each independent occurrence of is hydrogen, optionally substituted as defined below. 1-6 aliphatic, or unsubstituted 5-6 membered saturated, partially unsaturated, or aryl rings having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur).

[0029] R * Suitable substituents on the aliphatic group include halogen, -R ● ,-(Halo R ● ), -OH, -OR ●, -O(HaloR ● ), -CN, -C(O)OH, -C(O)OR ● , -NH2, -NHR ● , -NR ● 2, or -NO2, wherein each R ● is unsubstituted or, if preceded by "halo", is substituted only by one or more halogens, and independently, C 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, or a 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0030] Suitable substituents on a substitutable nitrogen of an "optionally substituted" group include -R † , -NR † 2. -C(O)R † , -C(O)OR † , -C(O)C(O)R † , -C(O)CHC(O)R † , -S(O)2R † , -S(O)NR † 2. -C(S)NR † 2. -C(NH)NR † 2, or -N(R † )S(O)2R † wherein each R † are independently hydrogen, optionally substituted as defined below, C 1-6 an aliphatic, unsubstituted -OPh, or unsubstituted 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, regardless of the above definitions, R † two independent occurrences of together with their intervening atoms form an unsubstituted 3-12 membered saturated, partially unsaturated or aryl monocyclic or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen or sulfur.

[0031] R † Suitable substituents on the aliphatic group are independently halogen, —R ●,-(Halo R ● ), -OH, -OR ● , -O(HaloR ● ), -CN, -C(O)OH, -C(O)OR ● , -NH2, -NHR ● , -NR ● 2, or -NO2, where each R ● is unsubstituted or, if preceded by "halo", is substituted only by one or more halogens, and independently, C 1-4 Aliphatic, -CH2Ph, -O(CH2) 0-1 Ph, or a 5-6 membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0032] As used herein, the term "provided compounds" refers to any genus, subgenus and / or species described herein.

[0033] As used herein, the term "pharmaceutically acceptable salt" refers to a salt that, within the scope of sound medical judgment, is suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic reaction, etc., and is commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S.M. Berge et al. describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1-19, which is incorporated herein by reference. Pharmaceutically acceptable salts of the compounds of the present disclosure include those derived from suitable inorganic and organic acids and bases. Examples of pharmaceutically acceptable non-toxic acid addition salts include salts of amino groups formed with inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid, and perchloric acid, or with organic acids such as acetic acid, trifluoroacetic acid (TFA), oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid, or by other methods used in the art, e.g., ion exchange. Other pharmaceutically acceptable salts include adipate, alginate, ascorbate, aspartate, benzenesulfonate, benzoate, bisulfate, borate, butyrate, camphorate, camphorsulfonate, citrate, cyclopentane-propionate, digluconate, dodecylsulfate, ethanesulfonate, formate, fumarate, glucoheptonate, glycerophosphate, gluconate, hemisulfate, heptanoate, hexanoate, hydroiodide, 2-hydroxy-ethanesulfonate, and the like. Salts include phosphate, lactobionate, lactate, laurate, lauryl sulfate, malate, maleate, malonate, methanesulfonate, 2-naphthalenesulfonate, nicotinate, nitrate, oleate, oxalate, palmitate, pamoate, pectinate, persulfate, 3-phenylpropionate, phosphate, pivalate, propionate, stearate, succinate, sulfate, tartrate, thiocyanate, p-toluenesulfonate, undecanoate, valerate, etc. In certain embodiments, some of the compounds disclosed herein are prepared as TFA salts.

[0034] Salts derived from appropriate bases include alkali metal salts, alkaline earth metal salts, ammonium salts and N + (C 1-4 Representative alkali metal or alkaline earth metal salts include sodium, lithium, potassium, calcium, magnesium, etc. Further pharmaceutically acceptable salts include, where appropriate, non-toxic ammonium, quaternary ammonium, and amine cations formed using counterions such as halides, hydroxides, carboxylates, sulfates, phosphates, nitrates, lower alkyl sulfonates, and aryl sulfonates.

[0035] Unless otherwise stated, structures depicted herein are also meant to include all isomeric (e.g., enantiomeric, diastereomeric, and geometric (or conformational)) forms of the structure, such as the R and S configurations of each asymmetric center, Z and E double bond isomers, and Z and E conformational isomers. Accordingly, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the disclosure. Unless otherwise stated, all tautomeric forms of the compounds of the disclosure are within the scope of the disclosure. Additionally, unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, replacement of hydrogen by deuterium or tritium, or 13 C-enriched carbon or 14 Compounds having this structure including the replacement of a carbon with a C-enriched carbon are within the scope of this disclosure. Such compounds are useful, for example, as analytical tools, probes in biological assays, or as therapeutic agents according to this disclosure.

[0036] As used herein, the term "antagonist" is defined as a compound that binds to and / or inhibits cGAS with measurable affinity. In certain embodiments, a cGAS antagonist has an IC50 and / or binding constant of less than about 30 μM or less than about 2 μM.

[0037] 3.2. Compounds of the Disclosure The disclosed compounds and compositions thereof are useful as cGAS antagonists. In some embodiments, provided compounds inhibit cGAS.

[0038] The present disclosure provides compounds of formula I: [ka] (In the formula: Ring A is an optionally substituted group selected from phenyl, HetAr and HetCy; HetAr is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, wherein the 5-6 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. the law of nature; R 2 is halogen, -OR, -NR2, -NRNR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -NRSO2R, -SR, -S02R, -S02NR2, -S(O)R, or R B , especially -NR2, or R B and; Each R 3 are independently halogen, -OR, -NR2, -SR, or R C , in particular halogen, for example chloro; R B and R C independently, C 1-6 aliphatic; phenyl; 4-10 membered saturated or partially unsaturated monocyclic or bicyclic rings containing 1-3 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur; Carbocyclic ring or a heterocyclic ring; and an optionally substituted group selected from a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; Each R is independently hydrogen or C 1-6 an optionally substituted group selected from aliphatic; benzyl; phenyl; a 4-10 membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur, or two R groups on the same nitrogen, optionally taken together with their intervening atoms, form an optionally substituted 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having, in addition to the nitrogen, 0-3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; n is 1, 2, 3 or 4; However, the compound is preferably one of the following: [ka] isn't it) or a pharmaceutically acceptable salt thereof.

[0039] In some embodiments, the compound defined above (i.e., the compound of Formula I or a pharmaceutically acceptable salt thereof) is not a compound specifically disclosed in International Application No. PCT / US2021 / 49084.

[0040] In certain embodiments, the present disclosure provides compounds of formula I, wherein ring A is optionally substituted phenyl, preferably substituted phenyl.

[0041] In certain embodiments, the present disclosure provides compounds of formula I, wherein Ring A is optionally substituted HetAr. For example, in certain embodiments, Ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted thienyl, furanyl, pyrrolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, pteridinyl, indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, and phenoxazinyl. In further such embodiments, Ring A is optionally substituted HetAr, where HetAr is selected from optionally substituted thienyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, and pyrimidinyl. In a preferred embodiment, Ring A is optionally substituted HetAr, where HetAr is selected from optionally substituted triazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl.

[0042] In certain embodiments, the present disclosure provides a compound wherein ring A is optionally may be substituted Compounds of formula I are provided in which HetCy is HetCy. For example, in certain embodiments, ring A is optionally substituted HetCy, where HetCy is optionally substituted tetrahydrofuranyl, tetrahydrothiophenyl, 、 Pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, quinuclidinyl 、 Indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, tetrahydroquinolinyl 、In further such embodiments, Ring A is optionally substituted HetCy, wherein HetCy is selected from optionally substituted morpholinyl, piperazinyl, 2,5-dihydro-1H-pyrrole, and 2,3-dihydro-1H-pyrrole.

[0043] In certain embodiments, the present disclosure provides compounds that are of formula I: Ring A is an optionally substituted group selected from phenyl, HetAr and HetCy; R 2 is R B and R B For example, halogen, =O, =CH2, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -OH, -(CH2) 1-2 -OH, -OC 1-4 Alkyl, -(CH2) 0-2 CO2H, -(CH2) 0-2 O(CH2) 1-5 CO2H, -(CH2) 0-2 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-2 CO2C 1-4 Alkyl, -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 is independently for each occurrence H, or C 1-4a substituted 4- to 7-membered saturated heterocyclic ring (e.g., monocyclic or bicyclic) having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur, substituted by one or two groups selected from the group consisting of alkyl, aryl, arylsulfonyl ... Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0044] In other embodiments, the present disclosure provides a compound of formula I: Ring A is an optionally substituted group selected from phenyl, HetAr and HetCy; R 2 is -NR2, where one R is H or lower alkyl (especially methyl) and the other R is optionally substituted -C 1-5 Substituted C containing alkylene-X 1-6 aliphatic; wherein X is -OH, -OC 1-4 Alkyl, -OC 1-4 Alkylene -COH, -OC 1-4 Alkylene-CO2C 1-4 Alkyl, -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, -P(O)(OH), and -OP(O)(H)(OH), wherein R ais independently for each occurrence H, or C 1-4 is alkyl; Each R 3 are independently halogen, e.g., chloro, including dichloro, e.g., n is 2; R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0045] In some embodiments, the disclosure provides a compound of formula I: Ring A is an optionally substituted group selected from phenyl, HetAr and HetCy; R 2 is R B and R B is an optionally substituted 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur (particularly imidazole or pyrazole, e.g., 1-imidazole, or 4-pyrazole); Each R 3 are independently halogen, e.g., chloro, including dichloro, e.g., n is 2; R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0046] In other embodiments, the present disclosure provides a compound of formula I: Ring A is an optionally substituted group selected from phenyl, HetAr and HetCy; R 2 is a substituted phenyl (especially halogen, C 1-4 Alkyl, -OH, -OC 1-4 Alkyl, -CO2H, -CO2C 1-4 Alkyl, -(CH2) 0-2 O(CH2) 1-5 CO2H, -(CH2) 0-2 O(CH2) 1-5 CO2C 1-4 substituted by one or two groups selected from alkyl, -NH2, and -CONH2); Each R 3are independently halogen, e.g., chloro, including dichloro, e.g., n is 2; R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0047] In other embodiments, the present disclosure provides a compound of formula I: Ring A is an optionally substituted group selected from phenyl, HetAr and HetCy; R 2 is R B and R B is optionally substituted C 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic (especially -(CR2) 1-4 NR(CR2) 0-6 CO2R); Each R 3 are independently halogen, e.g., chloro, including dichloro, e.g., n is 2; R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0048] In certain embodiments, the present disclosure provides compounds that are of formula I: Ring A is an optionally substituted group selected from phenyl, HetAr and HetCy; R 2 is -NR a R 5 , [ka] and; Each R 3 are independently halogen, -OR, -NR2, -SR, or R C and; Ring B1 is phenyl, preferably substituted phenyl; 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic rings having 1 to 3 heteroatoms independently selected from nitrogen, oxygen and sulfur; carbocyclica 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 C 1-6 an optionally substituted group selected from 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; 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 and; Each R 6 are independently halogen, =O, =CH2, C 1-4 Alkyl, C 1-4 Haloalkyl, C 3-6Cycloalkyl, -COR, -(CR2) 0-4 CO2R (e.g., -(CH2) 0-2 CO2H or -(CH2) 0-2 CO2C 1-4 alkyl), -(CH2) 0-2 O(CH2) 1-5 CO2H, -(CH2) 0-2 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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), -(CR2) 1-4 OR (e.g., -(CH2) 1-2 -OH), -NR2 (e.g., -NH2), -(CR2) 1-4 NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -SR, -SO2R, -S(O)R, -(CR2) 0-4 SO3R (e.g., -(CH2) 0-2 SO3H), -(CR2) 0-4 SO2NR2 (e.g., -(CH2) 0-2 SO2NH2 or -(CH2) 0-2 SO2NHC 1-4 alkyl), -(CR2) 0-4 OSO2NR2, -(CR2) 0-4 NRSO2R (e.g., -(CH2) 0-2 NR a SO2C 1-4 alkyl), -(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 and R a is independently for each occurrence H, or C 1-4 is alkyl; R B and R C independently, C 1-6 aliphatic; phenyl; 4-10 membered saturated or partially unsaturated monocyclic or bicyclic rings containing 1-3 heteroatoms independently selected from nitrogen, oxygen and sulfur; carbocyclic an optionally substituted group selected from a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R a are independently H or C 1-6 is alkyl; each m is 0, 1, 2, 3, or 4; n is 1, 2, 3 or 4; q is 0, 1 or 2.

[0049] In some embodiments, ring A is unsubstituted phenyl. In preferred embodiments, ring A is substituted phenyl. In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] In some embodiments, ring A is [ka] is.

[0050] In some embodiments, ring A is optionally substituted HetCy, where 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. In certain embodiments, ring A is unsubstituted HetCy. In other embodiments, ring A is substituted HetCy.

[0051] In some embodiments, ring A is an optionally substituted HetCy, where HetCy is a 4-7 membered saturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is an optionally substituted [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] is.

[0052] In other embodiments, ring A is an optionally substituted HetCy, where HetCy is a 4-7 membered partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur. In some embodiments, ring A is 、 may be substituted [ka] In some embodiments, ring A is、 may be substituted [ka] is.

[0053] In some embodiments, ring A is an optionally substituted HetAr, wherein HetAr is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and wherein the 5-6 membered heteroaryl ring is not imidazole or pyrazole. In certain embodiments, ring A is unsubstituted HetAr. In other embodiments, ring A is substituted HetAr. In some embodiments, ring A is 、 may be substituted [ka] In some embodiments, ring A is 、 may be substituted [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] In some embodiments, ring A is optionally substituted. [ka] is.

[0054] In some embodiments, ring A is selected from the groups shown in Table 1.

[0055] In some embodiments, ring A is selected from the groups shown in Table 2.

[0056] In some embodiments, R 3 At least one occurrence of is halogen, e.g., chloro or bromo. In some embodiments, R 3 At least one occurrence of R is chloro. 3At least one occurrence of R is bromo, such as at the 7-position relative to the quinoline ring. In some embodiments, n is 2 and both R 3 is halo, e.g., both R 3 In some embodiments, n is 2 and R 3 are chloro at the 7 and 8 positions relative to the quinoline ring. In some embodiments, n is 2 and R 3 One occurrence of is chloro and R 3 The other occurrence of is bromo, e.g., bromo at the 7-position and chloro at the 8-position relative to the quinoline ring. In some embodiments, n is 3 and R 3 All occurrences of are halo, for example bromo at the 6-position and chloro at the 7- and 8-positions relative to the quinoline ring.

[0057] In certain embodiments, R 3 At least one occurrence of C is optionally substituted, such as methyl. 1-6 In some embodiments, n is 2 and R 3 One occurrence of is a halo such as bromo, and R 3 The other occurrence of C is optionally substituted, such as methyl. 1-6 In some embodiments, n is 2 and R 3 One occurrence of is bromo at the 7-position relative to the quinoline ring, and R 3 The other occurrence of is a methyl at the 8-position relative to the quinoline ring.

[0058] In some embodiments, R 2 Ha-NR a R 5 is.

[0059] In some embodiments, R 5 is -(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) 0-4 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.

[0060] In some embodiments, R 5 is -(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) 0-4 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.

[0061] In some embodiments, R 5 is -(CH2) 2-4 OH, -(CH2) 2-4 O(CH2) 1-5 CO2H, -(CH2) 2-4 O(CH2) 1-5 CO2C 1-4Alkyl, -(CH2) 0-3 CH(CH2OH)2, -(CH2) 2-4 OC 1-4 Alkyl, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 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) 2-4 NR a SO3H, -(CH2) 1-4OP(OH)2, -(CH2) 1-4 P(O)(OH)2, -(CH2) 1-4 P(O)(OH)(OC 1-4 alkyl), or -(CH2) 2-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-6 It is alkyl.

[0062] In some embodiments, R 5 is -(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) 1-5 CO2H, -(CH2) 1-5 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) 2-4 NR a SO2C 1-4 Alkyl, -(CH2) 1-4 P(O)(OH)2, or -(CH2) 2-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 It is alkyl.

[0063] In some embodiments, R 2 teeth [ka] In some embodiments, m is 1, 2, 3, or 4.

[0064] In some embodiments, Ring B1 is a substituted phenyl. In some embodiments, the phenyl is substituted with one or more carboxyl groups.

[0065] In some embodiments, ring B1 is selected from the group consisting of one or more R 6 and a 3-carboxyphenyl group optionally substituted by a group.

[0066] In some embodiments, ring B1 is selected from the group consisting of one or more R 6 and 3,5-dicarboxyphenyl groups optionally substituted by groups.

[0067] In some embodiments, Ring B1 is a 4-10 membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0068] In some embodiments, Ring B1 is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0069] In some embodiments, R 2 teeth [ka] wherein X is absent (i.e., a bond within the ring), -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.

[0070] In some embodiments, each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -(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) 1-4 CONHC 1-4 Alkyl, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 alkyl), -OH, -(CH) 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 1-4Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 It is alkyl.

[0071] In some embodiments, each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -(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) 1-4 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, -(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 It is OP(O)(H)OH.

[0072] In some embodiments, R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, C 3-6 Cycloalkyl, -(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, R a is independently for each occurrence H, or C 1-4 It is alkyl.

[0073] In some embodiments, each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4Haloalkyl, C 3-6 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, -(CH2) 1-4 SO3H, -(CH2) 1-4 SO2NH2, -(CH2) 1-4 NR a SO2C 1-4 Alkyl, -(CH2) 1-4 OP(OH)2, or -(CR2) 1-4 It is OP(O)(H)OH.

[0074] In some embodiments, each R 6 are independently halogen, -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.

[0075] In some embodiments, R 2 teeth [ka] In some embodiments, m is 1, 2, 3, or 4. In some embodiments, m is 1 or 2.

[0076] In some embodiments, R 2 teeth [ka] In some embodiments, m is 1, 2, 3, or 4. In some embodiments, m is 1 or 2.

[0077] In some embodiments, each R 6 are independently 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, -(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)NRa (CH2) 1-4 CON(C 1-4 alkyl), -OH, -(CH) 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 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-6 It is alkyl.

[0078] In some embodiments, each R 6 are independently 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, -(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)-CO2H, -OH, -(CH2) 1-4 OH, -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 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 NR a SO2C 1-4 Alkyl, -(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, Ra is independently for each occurrence H, or C 1-4 It is alkyl.

[0079] In some embodiments, 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, and R a is independently for each occurrence H, or C 1-4 It is alkyl.

[0080] In some embodiments, each R 6 are independently fluoro, =O, =CH2, methyl, cyclohexyl, morpholinyl, phenyl, -CF3, -OMe, -OtBu, -CO2H, -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.

[0081] In some embodiments, Ring B1 is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a carbon atom of the 5-6 membered heteroaryl ring is directly bonded to the 2-carbon atom of the quinolone ring. 。

[0082] In some embodiments, Ring B1 is imidazole or pyrazole. In some embodiments, the imidazole or pyrazole is unsubstituted.

[0083] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] is.

[0084] In some embodiments, R 2 teeth [ka] In some embodiments, m is 1, 2, 3, or 4.

[0085] In some embodiments, ring B2 is phenyl.

[0086] In some embodiments, Ring B2 is a 4-7 membered saturated or partially unsaturated carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0087] In some embodiments, ring B2 is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0088] In some embodiments, R 2 teeth, [ka] wherein X is absent (i.e., a bond within the ring), -CR2-, -NR-, -O-, -S-, or -SO2-; and m is 1, 2, 3, or 4. In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, X is -CR2-, -NR-, or -O-. In some embodiments, q is 1 or 2. In some embodiments, q is 1. In some embodiments, m is 1 or 2.

[0089] In some embodiments, each R 6 are independently halogen, -(CH2) 0-4 CO2H, -(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), -OH, -(CH) 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) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 It is alkyl.

[0090] In some embodiments, each R 6 are independently halogen, -(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 NRa SO2C 1-4 Alkyl, -(CH2) 0-4 OP(OH)2, or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 It is alkyl.

[0091] In some embodiments, each R 6 are independently halogen, -COH, -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, and R a is independently for each occurrence H, or C 1-4 It is alkyl.

[0092] In some embodiments, R 6 is R B isn't it.

[0093] In some embodiments, m is at least 1 and at least one R 6 is a terminal -CO2H or -CO2C 1-4 Contains an alkyl group.

[0094] In some embodiments, at least one R 6 is -(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 It is alkyl.

[0095] In some embodiments, the present disclosure provides a pharmaceutical composition comprising a compound of formula I or a pharmaceutically acceptable salt thereof.

[0096] In some embodiments, the disclosure provides a method of antagonizing cyclic GMP-AMP synthase (cGAS) in a patient in need thereof, comprising administering an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0097] In some embodiments, the present disclosure provides a method of treating an inflammatory, allergic, or autoimmune disease in a patient in need thereof, comprising administering an effective amount of a compound of formula I or a pharmaceutically acceptable salt thereof, or a pharmaceutical composition thereof.

[0098] In some embodiments, the present disclosure provides R 2 is -NR2, thereby providing a compound of formula Ia-1: [ka] or a pharmaceutically acceptable salt thereof, wherein rings A, R, R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0099] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ia-1 in which the 7 and 8 positions are chloro relative to the quinoline ring.

[0100] In certain embodiments, the present disclosure provides a compound of formula Ia-1, wherein ring A is an optionally substituted phenyl, preferably a substituted phenyl. In certain embodiments, the present disclosure provides a compound of formula Ia-1, wherein ring A is an optionally substituted HetCy. In certain embodiments, the present disclosure provides a compound of formula Ia-1, wherein ring A is may be substituted Compounds of formula Ia-1 are provided in which HetAr is

[0101] In some embodiments, the present disclosure provides R 2 Ga-NRR 5 whereby a compound of formula Ia-2: [ka] or a pharmaceutically acceptable salt thereof, wherein: R 5 is -(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) 0-6 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; Ring A, R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0102] In certain embodiments, the present disclosure provides a compound of formula Ia-2, wherein ring A is an optionally substituted phenyl, preferably a substituted phenyl. In certain embodiments, the present disclosure provides a compound of formula Ia-2, wherein ring A is an optionally substituted HetCy. In certain embodiments, the present disclosure provides a compound of formula Ia-2, wherein ring A is may be substituted Compounds of formula Ia-2 are provided in which HetAr is

[0103] In certain embodiments, the present disclosure provides R 5 Ga-(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 The present invention provides a compound of formula Ia-2, wherein

[0104] In some embodiments, the present disclosure provides R 5 R B The present invention provides a compound of formula Ia-2, wherein:

[0105] In some embodiments, the present disclosure provides -NRR 5 R is H or C 1-6 R is alkyl aThe present invention provides a compound of formula Ia-2, wherein

[0106] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ia-1 in which the 7 and 8 positions are chloro relative to the quinoline ring.

[0107] In certain embodiments, the present disclosure provides compounds of formula Ia-2: -NRR 5 R is H or lower alkyl, especially methyl; R 5 is -(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) 0-6 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, or -(CR2) 0-6 OP(O)(H)OR; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0108] In certain embodiments, the present disclosure provides compounds of formula Ia-2: -NRR 5 R is H or lower alkyl, especially methyl; R 5 is -(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) 1-4 CO2C 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 1-4Alkyl, -(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) 2-4 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), or -(CH2) 2-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0109] In certain embodiments, the present disclosure provides compounds of formula Ia-2: -NRR 5 R is H or lower alkyl, especially methyl; R 5 is -(CH2) 2-4 OH, -(CH2) 0-3 CH(CH2OH)2, -(CH2) 2-4 OC 1-4 Alkyl, -(CH2) 1-4 CO2H, -(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 CONH2, -(CH2) 1-4 CONHC 1-4 Alkyl, -(CH2) 1-4 CON(C1-4 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) 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) 2-4 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), or -(CH2) 2-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0110] In further specific embodiments, the present disclosure provides compounds of formula Ia-2: -NRR 5 R is H or lower alkyl, especially methyl; R5 is -(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) 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) 2-4 NR a SO2C 1-4 Alkyl, -(CH2) 1-4 P(O)(OH)2, or -(CH2) 2-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0111] In further specific embodiments, the present disclosure provides compounds of formula Ia-2: -NRR 5 R is H or lower alkyl, especially methyl; R5 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) 1-4 CO2H, -(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, -(CH2) 2-4 NR a SO2C 1-4 Alkyl, -(CH2) 1-4 P(O)(OH)2, or -(CH2) 2-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0112] In certain embodiments, for the above-disclosed compounds of formula Ia-2, R 5 contains a terminal -COH group. For example, in certain cases, R 5 is the terminal -(CH2) 0-4 Contains CO2H groups.

[0113] In some embodiments, the present disclosure provides R 2 but [ka] whereby a compound of formula Ia-3: [ka] or a pharmaceutically acceptable salt thereof, wherein: Ring B1 is phenyl, preferably substituted phenyl; 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic rings having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus and sulfur; carbocyclic a cyclic or heterocyclic ring; or a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; Each R 6 are independently 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 and; m is 0, 1, 2, 3 or 4, in particular 1, 2, 3 or 4; Ring A, R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0114] In certain embodiments, the present disclosure provides a compound of formula Ia-3, wherein ring A is an optionally substituted phenyl, preferably a substituted phenyl. In certain embodiments, the present disclosure provides a compound of formula Ia-3, wherein ring A is an optionally substituted HetCy. In certain embodiments, the present disclosure provides a compound of formula Ia-3, wherein ring A is may be substituted Compounds of formula Ia-3 are provided in which HetAr is

[0115] In certain embodiments, the present disclosure provides compounds of formula Ia-3, where Ring B1 is phenyl, particularly substituted phenyl. In other embodiments, Ring B1 is not phenyl. For example, Ring B1 can be a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur. carbocyclic In some embodiments, Ring B1 is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur.

[0116] In some embodiments, the present disclosure provides R 6 R B The present invention provides a compound of formula Ia-3, wherein:

[0117] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ia-3, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0118] In certain embodiments, for the above-disclosed compounds of formula Ia-3, m is 1 or 2 and at least one R 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0119] In some embodiments, the present disclosure provides R 2 but [ka] whereby a compound of formula Ia-4: [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 6 are independently 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 and; m is 0, 1, 2, 3 or 4, in particular 1, 2, 3 or 4; Ring A, R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0120] In certain embodiments, the present disclosure provides a compound of formula Ia-4, wherein ring A is an optionally substituted phenyl, preferably a substituted phenyl. In certain embodiments, the present disclosure provides a compound of formula Ia-4, wherein ring A is an optionally substituted HetCy. In certain embodiments, the present disclosure provides a compound of formula Ia-4, wherein ring A is may be substituted Compounds of formula Ia-4 are provided in which HetAr.

[0121] In some embodiments, the present disclosure provides R 6 R B The present invention provides a compound of formula Ia-4, wherein:

[0122] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ia-4, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0123] In certain embodiments, for the above-disclosed compounds of formula Ia-4, m is 1 or 2 and at least one R 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0124] In some embodiments, the present disclosure provides R 2 but [ka] whereby a compound of formula Ia-5: [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 6 are independently 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 and; X is absent (i.e., a bond within the ring), -CR2-, -NR-, -O-, -S-, or -SO2-; particularly, -CR2-, -NR-, -O-, -S-, or -SO2-; more particularly, -CR2-, -NR-, or -O-; m is 0, 1, 2, 3 or 4, in particular 1, 2, 3 or 4; p is 0, 1 or 2, in particular 1; Ring A, R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0125] In certain embodiments, the present disclosure provides a compound of formula Ia-5, wherein ring A is an optionally substituted phenyl, preferably a substituted phenyl. In certain embodiments, the present disclosure provides a compound of formula Ia-5, wherein ring A is an optionally substituted HetCy. In certain embodiments, the present disclosure provides a compound of formula Ia-5, wherein ring A is may be substituted Compounds of formula Ia-5 are provided in which HetAr is

[0126] In some embodiments, the present disclosure provides R 6 R B The present invention provides a compound of formula Ia-5, wherein:

[0127] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ia-5, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0128] In certain embodiments, the present disclosure provides compounds of formula Ia-5: Each R 6 are independently halogen, -C 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) 0-6OP(O)(OR)2, -(CR2) 0-6 P(O)(OR)2, -(CR2) 0-6 OP(O)(H)OR, or -B(OR)2; m is 1, 2, 3 or 4, in particular 1 or 2; p is 0 or 1, in particular 1; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0129] In certain embodiments, the present disclosure provides compounds of formula Ia-5: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2)1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(CH2) 0-4 CON(C 1-4 alkyl)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, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4-O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 0-4 N[(CH2) 1-4 CO2C 1-4 alkyl]2, -(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, R a is independently for each occurrence H, or C1-4 is alkyl; X is -CH2-, -NH-, or -O-; m is 1, 2, 3, or 4, in particular 1 or 2; p is 1; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0130] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, -methoxy, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Compounds of formula Ia-5 are provided wherein m is 1, 2 or 3, particularly 1 or 2, and wherein m is alkyl, or —OH.

[0131] In certain embodiments, the present disclosure provides compounds of formula Ia-5: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 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 CONH2, -(CH2) 0-4 CONHC 1-4 Alkyl, -(CH2) 0-4CON(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), -OH, -(CH) 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) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; X is -CH2-, -NH-, or -O-; m is 1, 2, 3, or 4, in particular 1 or 2; p is 1; Each R 3 are independently optionally substituted C 1-6aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0132] In further specific embodiments, the present disclosure provides compounds of formula Ia-5: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(CH2) 0-4 OP(OH)2, or -(CR2) 0-4 OP(O)(H)OH; X is -CH2-, -NH-, or -O-; m is 1 or 2; p is 1; Each R 3 are independently halogen, e.g., chloro, including dichloro, e.g., n is 2; R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0133] In certain embodiments, for the above-disclosed compounds of formula Ia-5, m is 1 or 2 and at least one R 6contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0134] In certain embodiments, the present disclosure provides compounds of formula Ia-5: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(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), -OH, -(CH) 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, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC1-4 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, R a is independently for each occurrence H, or C 1-4 is alkyl; X is -CH2-, -NH-, or -O-; m is 1, 2, 3, or 4, in particular 1 or 2; p is 1; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0135] In further specific embodiments, the present disclosure provides compounds of formula Ia-5: Each R 6 are independently halogen, -C 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 CO2C1-4 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; X is -CH2-, -NH-, or -O-; m is 1 or 2; p is 1; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0136] In certain embodiments, for the above-disclosed compounds of formula Ia-5, m is 1 or 2 and at least one R 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0137] In certain embodiments, the present disclosure provides compounds of formula Ia-5: Each R 6 are independently halogen, =O, -(CH2) 0-4 CO2H, -(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)NRa (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), -OH, -(CH) 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) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; X is -CH2-, -NH-, or -O-; m is 1, 2, 3, or 4, in particular 1 or 2; p is 1; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0138] In further specific embodiments, the present disclosure provides compounds of formula Ia-5: Each R 6 are independently halogen, -(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, -(CH2) 0-4 OP(OH)2, or -(CR2) 0-4 OP(O)(H)OH; X is -CH2-, -NH-, or -O-; m is 1 or 2; p is 1; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0139] In certain embodiments, for the above-disclosed compounds of formula Ia-5, m is 1 or 2 and at least one R 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0140] In some embodiments, the present disclosure provides R 2 but [ka] whereby the compound of formula Ia-6: [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 6 are independently 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 m is 0, 1, 2, 3 or 4, in particular 1, 2, 3 or 4; Ring A, R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0141] In certain embodiments, the present disclosure provides compounds of formula Ia-6, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In certain embodiments, the present disclosure provides compounds of formula Ia-6, wherein ring A is optionally substituted HetCy. In certain embodiments, the present disclosure provides compounds of formula Ia-6, wherein ring A is optionally substituted HetCy. may be substituted Compounds of formula Ia-6 are provided in which HetAr.

[0142] In some embodiments, the present disclosure provides R 6 R B The present invention provides a compound of formula Ia-6, wherein:

[0143] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ia-6, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0144] In certain embodiments, the present disclosure provides compounds of formula Ia-6: Each R 6 are independently halogen, -C 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; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0145] In certain embodiments, the present disclosure provides compounds of formula Ia-6: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(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 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4-O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 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) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0146] In further specific embodiments, the present disclosure provides compounds of formula Ia-6: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(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) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 alkyl)-CO2H, -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 CO2C1-4 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0147] In certain embodiments, the present disclosure provides compounds of formula Ia-6: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO2C 1-4 Haloalkyl, -(CH2) 0-4 O(CH2) 1-5CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(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 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 1-4 Alkyl, -NH2, -(CH2) 0-4NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0148] In further specific embodiments, the present disclosure provides compounds of formula Ia-6: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0149] In further specific embodiments, the present disclosure provides that each R 6 are independently fluoro, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Compounds of formula Ia-6 are provided in which m is 1, 2 or 3, particularly 1 or 2, and m is alkyl or —OH.

[0150] In certain embodiments, the present disclosure provides compounds of formula Ia-6: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 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 CONH2, -(CH2) 0-4 CONHC1-4 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), -OH, -(CH) 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 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) 0-4 NR a SO2C 1-4 Alkyl, -(CH2) 0-4 NRa 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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 alkyl; m is 1, 2, 3 or 4, especially 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0151] In further specific embodiments, the present disclosure provides compounds of formula Ia-6: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 1-4Alkyl, -(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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0152] In certain embodiments, the present disclosure provides compounds of formula Ia-6: Each R 6 are independently 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) 0-6OSO2NR2, -(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 -B(OR)2; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0153] In certain embodiments, the present disclosure provides compounds of formula Ia-6: Each R 6 are independently halogen, =O, -(CH2) 0-4 CO2H, -(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 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 1-4Alkyl, -(CH2) 0-4 C(O)NR a (CH2) 1-4 CON(C 1-4 alkyl), -OH, -(CH) 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 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 alkyl; m is 1, 2, 3 or 4, especially 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0154] In further specific embodiments, the present disclosure provides compounds of formula Ia-6: Each R 6 are independently halogen, -(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)-CO2H, -OH, -(CH2) 1-4 OH, -(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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0155] In certain embodiments, the present disclosure provides compounds of formula Ia-6: m is 1; R 6 is -(CH2) 0-4 O(CH2) 1-5 CO2H, for example, -(CH2), including -CH2O(CH2)2CO2H 1-2 O(CH2) 2-3 CO2H; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0156] In certain embodiments, for the above-disclosed compounds of formula Ia-6, m is 1 or 2 and at least one R 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0157] In certain embodiments, the present disclosure provides a compound wherein n is 2 and R 3 are chloro at the 7th and 8th positions relative to the quinoline ring, and R 6 An example of this is -(CH2) 0-4 O(CH2) 1-5 In some such embodiments, the compound of formula Ia-6 is of formula Ia-6, wherein * Compounds of: [ka] or a pharmaceutically acceptable salt thereof, wherein: Ring A, R 6 and m, alone and in combination, are as defined above and described in embodiments herein. In certain embodiments, m is preferably zero.

[0158] In certain embodiments, the present disclosure provides compounds of formula Ia-6, wherein ring A is an optionally substituted phenyl, preferably a substituted phenyl. * In certain embodiments, the present disclosure provides compounds of formula Ia-6, wherein ring A is optionally substituted HetCy. * In certain embodiments, the present disclosure provides compounds wherein ring A is optionally may be substituted Formula Ia-6, where HetAr * The present invention provides a compound of the formula:

[0159] In some embodiments, the present disclosure provides R 2 but [ka] whereby the compound of formula Ia-7: [ka] or a pharmaceutically acceptable salt thereof, wherein: 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, phosphorus, and sulfur; or a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; Each R 6 are independently halogen, -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 m is 0, 1, 2, 3 or 4, in particular 1, 2, 3 or 4; q is 0, 1 or 2; Ring A, R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0160] In certain embodiments, the present disclosure provides compounds of formula Ia-7, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In certain embodiments, the present disclosure provides compounds of formula Ia-7, wherein ring A is optionally substituted HetCy. In certain embodiments, the present disclosure provides compounds of formula Ia-7, wherein ring A is optionally substituted HetCy. may be substituted Compounds of formula Ia-7 are provided in which HetAr.

[0161] In certain embodiments, the present disclosure provides compounds of formula Ia-7 in which ring B2 is phenyl, particularly substituted phenyl. In other embodiments, ring B2 is not phenyl. For example, ring B2 can be a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic ring having 1 to 3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur. carbocyclic In some embodiments, Ring B2 is a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur.

[0162] In some embodiments, the present disclosure provides R 6 R B The present invention provides a compound of formula Ia-7, wherein:

[0163] In some embodiments, the present disclosure provides: [ka] R is H or C 1-6 R is alkyl a The present invention provides a compound of formula Ia-7,

[0164] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ia-7, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0165] In certain embodiments, for the above-disclosed compounds of formula Ia-7, m is 1 or 2 and at least one R 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0166] In some embodiments, the present disclosure provides R 2 but [ka] and thereby have formula Ia-8 or formula Ia-8, respectively. * Compounds of: [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 6 are independently hydrogen (only on N), halogen (not on N), -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 and; X is absent (i.e., a bond within the ring), -CR2-, -NR-, -O-, -S-, or -SO2-, in particular -CR2-, -NR-, or -O; m is 1, 2, 3, or 4; q is 0, 1 or 2; Ring A, R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0167] In certain embodiments, the present disclosure provides compounds of formula Ia-8 or Ia-8, wherein ring A is an optionally substituted phenyl, preferably a substituted phenyl. * In certain embodiments, the present disclosure provides compounds of formula Ia-8 or Ia-8, wherein ring A is optionally substituted HetCy. *In certain embodiments, the present disclosure provides compounds wherein ring A is optionally may be substituted Formula Ia-8 or Formula Ia-8 * The present invention provides a compound of the formula:

[0168] In some embodiments, the present disclosure provides R 6 R B Formula Ia-8 or Formula Ia-8 * The present invention provides a compound of the formula:

[0169] In some embodiments, the present disclosure provides: [ka] R is H or C 1-6 R is alkyl a Formula Ia-8 or Formula Ia-8 * The present invention provides a compound of the formula:

[0170] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7- and 8-positions relative to the quinoline ring; or * The present invention provides a compound of the formula:

[0171] In certain embodiments, the present disclosure provides a compound of formula Ia-8 or formula Ia-8 * providing a compound of the formula: Each R 6 are independently 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) 0-6SO3R, -(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; m is 1, 2, 3 or 4, in particular 1 or 2; q is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0172] In certain embodiments, the present disclosure provides compounds of formula Ia-8 or formula Ia-8 * providing a compound of the formula: Each R 6 are independently halogen, =O, -(CH2) 0-4 CO2H, -(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), -OH, -(CH) 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) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 alkyl; m is 1, 2, 3 or 4, especially 1 or 2; q is 1; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0173] In further specific embodiments, the present disclosure provides compounds of formula Ia-8 or formula Ia-8 * providing a compound of the formula: Each R 6 are independently halogen, -(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, -(CH2) 0-4 OP(OH)2, or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 alkyl; m is 1 or 2; q is 1; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0174] In certain embodiments, the compound of formula Ia-8 or Ia-8 * For the above disclosed compounds of 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0175] In some embodiments, the present disclosure provides R 2 but [ka] whereby the compound of formula Ia-9: [ka] or a pharmaceutically acceptable salt thereof, wherein ring A, R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0176] In certain embodiments, the present disclosure provides compounds of formula Ia-9, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In certain embodiments, the present disclosure provides compounds of formula Ia-9, wherein ring A is optionally substituted HetCy. In certain embodiments, the present disclosure provides compounds of formula Ia-9, wherein ring A is optionally substituted HetCy. may be substituted Compounds of formula Ia-9 are provided in which HetAr.

[0177] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ia-9 in which the chloro is at the 7- and 8-position relative to the quinoline ring.

[0178] In some embodiments, the present disclosure provides R 2 but [ka] whereby a compound of formula Ia-10: [ka] or a pharmaceutically acceptable salt thereof, wherein: Ring C is pyrrolyl or a 4-10 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocyclic ring having 0-3 heteroatoms (in addition to the nitrogen already shown for Ring C) independently selected from nitrogen, oxygen and sulfur; Each R 6are independently 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 m is 1, 2, 3 or 4; Ring A, R, R B , R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0179] In certain embodiments, the present disclosure provides compounds of formula Ia-10, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In certain embodiments, the present disclosure provides compounds of formula Ia-10, wherein ring A is optionally substituted HetCy. In certain embodiments, the present disclosure provides compounds of formula Ia-10, wherein ring A is optionally substituted HetCy. may be substituted Compounds of formula Ia-10 are provided in which HetAr is

[0180] In some embodiments, the present disclosure provides compounds of Formula Ia-10, where Ring C is azetidinyl, pyrrolyl, 2,3-dihydro-1H-pyrrolyl, pyrrolidinyl, piperidinyl, morpholinyl, thiazolidinyl, indolinyl, isoindolinyl, octahydroindolyl, azepanyl, oxazepane, azabicyclohexane, azabicycloheptane, azabicyclooctane, azabicyclononane, azaspiroheptane, or octahydrocyclicpentapyrrole.

[0181] In certain embodiments, the present disclosure provides compounds of formula Ia-10, where Ring C is pyrrolyl, 2-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptanyl, or octahydrocyclopenta[b]pyrrolyl.

[0182] In certain embodiments, the present disclosure provides a compound in which ring C is 3-hydroxyproline, C 1-6 Alkyl 3-hydroxyproline ester, or C 1-6 Compounds of formula Ia-10, which are haloalkyl 3-hydroxyproline esters, are provided.

[0183] In some embodiments, the disclosure provides a compound of formula Ia-10: Each R 6 are independently fluoro, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, =CH2, =O, tetrazolyl, imidazolyl, thiophenyl, 1,2,4-oxadiazol-3(2H)-onyl, morpholinyl, phenyl, -(CH2) 1-4 OC 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(CH2) 0-4 CHCHCO2H, -(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Haloalkyl, -OCOC 1-4 Alkyl, -O(CH2) 1-4CO2H, -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, -(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, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolid-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, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2, -(CH2) 0-4 CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(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, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4.

[0184] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Compounds of formula Ia-10 are provided wherein m is 1, 2 or 3, particularly 1 or 2, and wherein m is haloalkyl, or —OH.

[0185] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -methoxy, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Compounds of formula Ia-10 are provided wherein m is 1, 2 or 3, particularly 1 or 2, and wherein m is alkyl, or —OH.

[0186] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ia-10, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0187] In some embodiments, the present disclosure provides R 2 but [ka] whereby a compound of formula Ia-11: [ka] or a pharmaceutically acceptable salt thereof, wherein: Ring C is pyrrolyl or a 4-10 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocyclic ring having 0-3 heteroatoms (in addition to the nitrogen already shown for Ring C) independently selected from nitrogen, oxygen and sulfur; Each R 6 are independently 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 m is 0, 1, 2 or 3; Ring A, R, R B , R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0188] In certain embodiments, the present disclosure provides compounds of formula Ia-11, wherein ring A is optionally substituted phenyl, preferably substituted phenyl.

[0189] In certain embodiments, the present disclosure provides compounds of formula Ia-11, wherein ring A is optionally substituted HetCy. For example, in certain embodiments, ring A is optionally substituted HetCy, wherein HetCy is optionally substituted tetrahydrofuranyl, tetrahydrothiophenyl, or the like. 、 Pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, quinuclidinyl 、 Indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, tetrahydroquinolinyl 、 In further such embodiments, Ring A is optionally substituted HetCy, wherein HetCy is selected from optionally substituted morpholinyl, piperazinyl, 2,5-dihydro-1H-pyrrole, and 2,3-dihydro-1H-pyrrole.

[0190] In certain embodiments, the present disclosure provides a compound wherein ring A is optionally may be substitutedProvided is a compound of formula Ia-11, wherein HetAr. For example, in certain embodiments, ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted thienyl, furanyl, pyrrolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, pteridinyl, indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, and phenoxazinyl. In further such embodiments, Ring A is optionally substituted HetAr, where HetAr is selected from optionally substituted thienyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, and pyrimidinyl. In a preferred embodiment, Ring A is optionally substituted HetAr, where HetAr is selected from optionally substituted triazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl.

[0191] In some embodiments, the disclosure provides compounds of Formula Ia-11, wherein Ring C is azetidinyl, pyrrolyl, 2,3-dihydro-1H-pyrrolyl, pyrrolidinyl, piperidinyl, morpholinyl, thiazolidinyl, indolinyl, isoindolinyl, octahydroindolyl, azepanyl, oxazepane, azabicyclohexane, azabicycloheptane, azabicyclooctane, azabicyclononane, azaspiroheptane, or octahydrocyclicpentapyrrole.

[0192] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, =O, =CH2, -cyclohexyl, phenyl, morpholinyl, -OMe, -OtBu, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C1-4 Compounds of formula Ia-11 are provided wherein m is haloalkyl, or —OH, and m is 0 or 1, or 2, particularly 0 or 1.

[0193] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ia-11, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0194] In some embodiments, the present disclosure provides a compound comprising at least one R 3 is halogen, for example chloro at the 8-position, thereby providing compounds of formula Ib-1: [ka] or a pharmaceutically acceptable salt thereof, wherein, alone and in combination, rings A, R 2 and R 3 are as defined above and described in embodiments herein, and n is 0, 1, 2, or 3.

[0195] In certain embodiments, the present disclosure provides compounds of formula Ib-1, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In certain embodiments, the present disclosure provides compounds of formula Ib-1, wherein ring A is optionally substituted HetCy. In certain embodiments, the present disclosure provides compounds of formula Ib-1, wherein ring A is optionally substituted HetCy. may be substituted Compounds of formula Ib-1 are provided in which HetAr is

[0196] In certain embodiments, the present disclosure provides R 2 R B and R B may be substituted C 1-6 Aliphatic, preferably substituted C 1-6Aliphatic, e.g., (CR2) 1-4 NR(CR2) 0-6 CO2R, -(CR2) 1-4 O(CR2) 0-4 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), especially -(CR) 1-4 NR(CR2) 0-4 CO2R, or -(CR2) 1-4 Compounds of formula Ib-1 are provided, wherein R is COR. In some embodiments, R 2 is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a , for example, -(CH2) 1-4 NR a (CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2R a , for example, -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CR2) 1-4 CO2R, e.g., -(CH2) 1-4 Contains CO2H-(CR2) 1-4 In certain embodiments, R 2 contains a terminal -COH group. For example, in certain cases, R 2is the terminal -(CH2) 0-4 Contains CO2H groups.

[0197] In some embodiments, the present disclosure provides a method for treating a cancer cell comprising administering to a patient a cancer treatment, ... a method for treating a cancer cell comprising administering to a patient a cancer treatment, 3 is chloro at the 7 and 8 positions, thereby providing compounds of formula Ib-2: [ka] or a pharmaceutically acceptable salt thereof, wherein rings A and R 2 Each of the above, alone and in combination, is as defined above and described in the embodiments herein.

[0198] In certain embodiments, the present disclosure provides compounds of formula Ib-2, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In certain embodiments, the present disclosure provides compounds of formula Ib-2, wherein ring A is optionally substituted HetCy. In certain embodiments, the present disclosure provides compounds of formula Ib-2, wherein ring A is optionally substituted HetCy. may be substituted Compounds of formula Ib-2 are provided in which HetAr is

[0199] In certain embodiments, the present disclosure provides R 2 R B and R B may be substituted C 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic, e.g., (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), especially -(CR)1-4 NR(CR2) 0-6 CO2R, or -(CR2) 1-4 Compounds of formula Ib-2 are provided, wherein R is COR. In some embodiments, R 2 is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a , for example, -(CH2) 1-4 NR a (CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2R a , for example, -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CR2) 1-4 CO2R, e.g., -(CH2) 1-4 Contains CO2H-(CR2) 1-4 In certain embodiments, R 2 contains a terminal -COH group. For example, in certain cases, R 2 is the terminal -(CH2) 0-4 Contains CO2H groups.

[0200] In some embodiments, the present disclosure provides R 2 but [ka] and R 3 is chloro at the 7 and 8 positions, thereby providing a compound of formula Ic-1: [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 6 are independently 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 m is 1, 2, 3 or 4; Rings A, R and R B Each of the above, alone and in combination, is as defined above and described in the embodiments herein.

[0201] In certain embodiments, the present disclosure provides compounds of formula Ic-1, wherein ring A is optionally substituted phenyl, preferably substituted phenyl.

[0202] In certain embodiments, the present disclosure provides compounds of formula Ic-1, wherein ring A is optionally substituted HetCy. For example, in certain embodiments, ring A is optionally substituted HetCy, wherein HetCy is optionally substituted tetrahydrofuranyl, tetrahydrothiophenyl, or the like. 、Pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, quinuclidinyl 、 Indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, tetrahydroquinolinyl 、 In further such embodiments, Ring A is optionally substituted HetCy, wherein HetCy is selected from optionally substituted morpholinyl, piperazinyl, 2,5-dihydro-1H-pyrrole, and 2,3-dihydro-1H-pyrrole.

[0203] In certain embodiments, the present disclosure provides a compound wherein ring A is optionally may be substitutedProvided is a compound of formula Ic-1, wherein HetAr. For example, in certain embodiments, ring A is optionally substituted HetAr, and HetAr is selected from optionally substituted thienyl, furanyl, pyrrolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, pteridinyl, indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl and phenoxazinyl. In further such embodiments, Ring A is optionally substituted HetAr, where HetAr is selected from optionally substituted thienyl, triazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyridazinyl, and pyrimidinyl. In a preferred embodiment, Ring A is optionally substituted HetAr, where HetAr is selected from optionally substituted triazolyl, oxazolyl, isoxazolyl, thiazolyl, and isothiazolyl.

[0204] In some embodiments, the present disclosure provides a compound of formula Ic-1: Each R 6 are independently fluoro, -CN, methyl, =O, =CH2, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, tetrazolyl, imidazolyl, thiophenyl, 1,2,4-oxadiazol-3(2H)-onyl, morpholinyl, phenyl, -(CH2) 1-4 OC 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2)1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(CH2) 0-4 CHCHCO2H, -(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Haloalkyl, -OCOC 1-4 Alkyl, -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, -(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, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolid-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, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2, -(CH2) 0-4 CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO-(N-piperidine)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(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) 1-4 CO2H, -(CH2)0-4 NR a SO2(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4.

[0205] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, =O, =CH2, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Compounds of formula Ic-1 are provided wherein m is haloalkyl, or —OH, and m is 1, 2 or 3, particularly 1 or 2.

[0206] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, ═O, ═CH2, -methyl, cyclohexyl, -CF3, -methoxy, -OtBu, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-5 CONR a 2, or —OH, and m is 1, 2 or 3, in particular 1 or 2.

[0207] In certain embodiments, the present disclosure provides a compound wherein m is 1 and R 6 But -(CH2) 0-4 O(CH2) 1-5CO2H, for example, -(CH2), including -CH2O(CH2)2CO2H 1-2 O(CH2) 2-3 Provided is a compound of formula Ic-1, which is CO2H.

[0208] In some embodiments, the present disclosure provides R 2 Ga-NRR 5 and R 3 is chloro at the 7 and 8 positions, thereby providing a compound of formula Ic-2: [ka] or a pharmaceutically acceptable salt thereof, wherein: R 5 is -(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) 0-6 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 and; Rings A, R and R B Each of the above, alone and in combination, is as defined above and described in the embodiments herein.

[0209] In certain embodiments, the present disclosure provides compounds of formula Ic-2, wherein ring A is optionally substituted phenyl, preferably substituted phenyl. In certain embodiments, the present disclosure provides compounds of formula Ic-2, wherein ring A is optionally substituted HetCy. In certain embodiments, the present disclosure provides compounds of formula Ic-2, wherein ring A is optionally substituted HetCy. may be substituted Compounds of formula Ic-2 are provided in which HetAr is

[0210] In some embodiments, the present disclosure provides R 5 R B provides a compound of formula Ic-2, wherein:

[0211] In certain embodiments, the present disclosure provides compounds of formula Ic-2, wherein R 5 is -(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) 1-4 CO2C 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 (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, -(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) 1-4 C(O)NR a (CH2) 2-4 SO2NH2, -(CH2) 1-4 CO(N-pyrrolidine)-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 (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, -(CH2) 2-4 NR a SO2(CH2) 2-4 OH, -(CH2) 2-4 NR a SO2(CH2) 2-4 OC 1-4Alkyl, -(CH2) 2-4 NR a SO2(CH2) 2-4 CO2H, -(CH2) 2-4 NR a SO2(benzene)-CO2H, -(CH2) 2-4 NR a SO2(benzene)-CO2C 1-4 Alkyl, -(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, -(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), or -(CH2) 2-4 OP(O)(H)OH, R a independently for each occurrence, H, C 1-4 Alkyl, or -SO2C 1-4 It is alkyl.

[0212] In some embodiments, the present disclosure provides -NRR 5 R is H or C 1-6 R is alkyl, especially methyl a The compound of formula Ic-2 is provided:

[0213] In some embodiments, the present disclosure provides that ring A is [ka] and thereby obtaining a compound of formula Id-1: [ka] or a pharmaceutically acceptable salt thereof, 2 , R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0214] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Id-1, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0215] In certain embodiments, the present disclosure provides R 2 R B and R B may be substituted C 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic, e.g., (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), especially -(CR) 1-4 NR(CR2) 0-6 CO2R, or -(CR2) 1-4 Compounds of formula Id-1 are provided, wherein R is COR. In some embodiments, R2 is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a , for example, -(CH2) 1-4 NR a (CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2R a , for example, -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CR2) 1-4 CO2R, e.g., -(CH2) 1-4 Contains CO2H-(CR2) 1-4 In certain embodiments, R 2 contains a terminal -COH group. For example, in certain cases, R 2 is the terminal -(CH2) 0-4 Contains CO2H groups.

[0216] In some embodiments, the present disclosure provides that ring A is [ka] and thereby obtaining a compound of formula Id-2: [ka] or a pharmaceutically acceptable salt thereof, wherein R 2 , R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0217] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Id-2, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0218] In certain embodiments, the present disclosure provides R 2 R B and R B may be substituted C 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic, e.g., (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), especially -(CR) 1-4 NR(CR2) 0-6 CO2R, or -(CR2) 1-4 Compounds of formula Id-2 are provided, wherein R is COR. In some embodiments, R 2 is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a , for example, -(CH2) 1-4 NR a (CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CH2)1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2R a , for example, -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CR2) 1-4 CO2R, e.g., -(CH2) 1-4 Contains CO2H-(CR2) 1-4 In certain embodiments, R 2 contains a terminal -COH group. For example, in certain cases, R 2 is the terminal -(CH2) 0-4 Contains CO2H groups.

[0219] In some embodiments, the present disclosure provides that ring A is [ka] and thereby obtaining a compound of formula Id-3: [ka] or a pharmaceutically acceptable salt thereof, wherein R 2 , R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0220] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Id-3, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0221] In certain embodiments, the present disclosure provides R 2 R B and R B may be substituted C 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic, e.g., (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), especially -(CR) 1-4 NR(CR2) 0-6 CO2R, or -(CR2) 1-4 Compounds of formula Id-3 are provided, wherein R is COR. In some embodiments, R 2 is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a , for example, -(CH2) 1-4 NR a (CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2R a , for example, -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CR2)1-4 CO2R, e.g., -(CH2) 1-4 Contains CO2H-(CR2) 1-4 In certain embodiments, R 2 contains a terminal -COH group. For example, in certain cases, R 2 is the terminal -(CH2) 0-4 Contains CO2H groups.

[0222] In some embodiments, the present disclosure provides that ring A is [ka] and thereby formula Id-4 or Id-4 * Compounds of: [ka] or a pharmaceutically acceptable salt thereof, wherein R 2 , R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0223] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7- and 8-positions relative to the quinoline ring; or * The present invention provides a compound of the formula:

[0224] In certain embodiments, the present disclosure provides R 2 R B and R B may be substituted C 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic, e.g., (CR2) 1-4 NR(CR2) 0-6CO2R, -(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), especially -(CR) 1-4 NR(CR2) 0-6 CO2R, or -(CR2) 1-4 Formula Id-4 or Id-4, which is CO2R * In some embodiments, R 2 is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a , for example, -(CH2) 1-4 NR a (CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2R a , for example, -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CR2) 1-4 CO2R, e.g., -(CH2) 1-4 Contains CO2H-(CR2) 1-4 In certain embodiments, R 2 contains a terminal -COH group. For example, in certain cases, R 2 is the terminal -(CH2) 0-4Contains CO2H groups.

[0225] In some embodiments, the present disclosure provides that ring A is [ka] and thereby formula Id-5 or Id-5 * Compounds of: [ka] or a pharmaceutically acceptable salt thereof, wherein R 2 , R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0226] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7- and 8-positions relative to the quinoline ring; or * The present invention provides a compound of the formula:

[0227] In certain embodiments, the present disclosure provides R 2 R B and R B may be substituted C 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic, e.g., (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) 1-4C(O)NHC 1-4 Alkyl, or -(CR2) 1-4 C(O)N(C 1-4 alkyl), especially -(CR) 1-4 NR(CR2) 0-6 CO2R, or -(CR2) 1-4 Formula Id-5 or Id-5, which is CO2R * In some embodiments, R 2 is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a , for example, -(CH2) 1-4 NR a (CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2R a , for example, -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CR2) 1-4 CO2R, e.g., -(CH2) 1-4 Contains CO2H-(CR2) 1-4 In certain embodiments, R 2 contains a terminal -COH group. For example, in certain cases, R 2 is the terminal -(CH2) 0-4 Contains CO2H groups.

[0228] In some embodiments, the present disclosure provides that ring A is [ka] and R 2 but [ka] whereby the compound of formula Ie-1: [ka] or a pharmaceutically acceptable salt thereof, wherein: Ring C is pyrrolyl or a 4-10 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocyclic ring having 0-3 heteroatoms (in addition to the nitrogen already shown for Ring C) independently selected from nitrogen, oxygen and sulfur; Each R 6 are independently 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 and; m is 1, 2, 3 or 4; R, R B , R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0229] In some embodiments, the present disclosure provides compounds of formula Ie-1, wherein Ring C is azetidinyl, pyrrolyl, 2,3-dihydro-1H-pyrrolyl, pyrrolidinyl, piperidinyl, morpholinyl, thiazolidinyl, indolinyl, isoindolinyl, octahydroindolyl, azepanyl, oxazepane, azabicyclohexane, azabicycloheptane, azabicyclooctane, azabicyclononane, azaspiroheptane, or octahydrocyclicpentapyrrole.

[0230] In certain embodiments, the present disclosure provides compounds of formula Ie-1, where Ring C is pyrrolyl, 2-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptanyl, or octahydrocyclopenta[b]pyrrolyl.

[0231] In certain embodiments, the present disclosure provides a compound in which ring C is 3-hydroxyproline, C 1-6 Alkyl 3-hydroxyproline ester, or C 1-6 Compounds of formula Ie-1 are provided which are haloalkyl 3-hydroxyproline esters.

[0232] In some embodiments, the disclosure provides a compound of formula Ie-1: Each R 6 are independently fluoro, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, =CH2, =O, tetrazolyl, imidazolyl, thiophenyl, 1,2,4-oxadiazol-3(2H)-onyl, morpholinyl, phenyl, -(CH2) 1-4 OC 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2)1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(CH2) 0-4 CHCHCO2H, -(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Haloalkyl, -OCOC 1-4 Alkyl, -O(CH2) 1-4 CO2H, -O(CH2) 1-4 CO2C1-4 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, -(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, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolid-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, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4Alkyl, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2, -(CH2) 0-4 CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(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) 1-4CO2C 1-4 Alkyl, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4.

[0233] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Compounds of formula Ie-1 are provided in which m is haloalkyl, or —OH, and m is 1, 2 or 3, particularly 1 or 2.

[0234] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -methoxy, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Compounds of formula Ie-1 are provided in which m is 1, 2 or 3, in particular 1 or 2, and is alkyl or —OH.

[0235] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ie-1, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0236] In some embodiments, the present disclosure provides that ring A is [ka] and R 2 but [ka] whereby a compound of formula Ie-2: [ka] or a pharmaceutically acceptable salt thereof, wherein: Ring C is pyrrolyl or a 4-10 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocyclic ring having 0-3 heteroatoms (in addition to the nitrogen already shown for Ring C) independently selected from nitrogen, oxygen and sulfur; Each R 6 are independently 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 and; m is 1, 2, 3 or 4; R, R B , R3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0237] In some embodiments, the present disclosure provides compounds of formula Ie-2, where Ring C is azetidinyl, pyrrolyl, 2,3-dihydro-1H-pyrrolyl, pyrrolidinyl, piperidinyl, morpholinyl, thiazolidinyl, indolinyl, isoindolinyl, octahydroindolyl, azepanyl, oxazepane, azabicyclohexane, azabicycloheptane, azabicyclooctane, azabicyclononane, azaspiroheptane, or octahydrocyclicpentapyrrole.

[0238] In certain embodiments, the present disclosure provides compounds of formula Ie-2, where Ring C is pyrrolyl, 2-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptanyl, or octahydrocyclopenta[b]pyrrolyl.

[0239] In certain embodiments, the present disclosure provides a compound in which ring C is 3-hydroxyproline, C 1-6 Alkyl 3-hydroxyproline ester, or C 1-6 Compounds of formula Ie-2, which are haloalkyl 3-hydroxyproline esters, are provided.

[0240] In some embodiments, the disclosure provides compounds of formula Ie-2: Each R 6 are independently fluoro, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, =CH2, =O, tetrazolyl, imidazolyl, thiophenyl, 1,2,4-oxadiazol-3(2H)-onyl, morpholinyl, phenyl, -(CH2) 1-4 OC 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(CH2) 0-4 CHCHCO2H, -(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C1-4 Haloalkyl, -OCOC 1-4 Alkyl, -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, -(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, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolid-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, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4(N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2, -(CH2) 0-4 CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(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 NRa SO2(CH2) 1-4 CO2H, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4.

[0241] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Compounds of formula Ie-2 are provided in which m is haloalkyl, or —OH, and m is 1, 2 or 3, particularly 1 or 2.

[0242] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -methoxy, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Compounds of formula Ie-2 are provided in which m is alkyl, or —OH, and m is 1, 2 or 3, particularly 1 or 2.

[0243] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3provides compounds Ie-2, which are chloro at the 7- and 8-positions relative to the quinoline ring.

[0244] In some embodiments, the present disclosure provides that ring A is [ka] and R 2 but [ka] whereby a compound of formula Ie-3: [ka] or a pharmaceutically acceptable salt thereof, wherein: Ring C is pyrrolyl or a 4-10 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocyclic ring having 0-3 heteroatoms (in addition to the nitrogen already shown for Ring C) independently selected from nitrogen, oxygen and sulfur; Each R 6 are independently 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 and; m is 1, 2, 3 or 4; R, R B , R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0245] In some embodiments, the present disclosure provides compounds of formula Ie-3, wherein Ring C is azetidinyl, pyrrolyl, 2,3-dihydro-1H-pyrrolyl, pyrrolidinyl, piperidinyl, morpholinyl, thiazolidinyl, indolinyl, isoindolinyl, octahydroindolyl, azepanyl, oxazepane, azabicyclohexane, azabicycloheptane, azabicyclooctane, azabicyclononane, azaspiroheptane, or octahydrocyclicpentapyrrole.

[0246] In certain embodiments, the present disclosure provides compounds of formula Ie-3, where Ring C is pyrrolyl, 2-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptanyl, or octahydrocyclopenta[b]pyrrolyl.

[0247] In certain embodiments, the present disclosure provides a compound in which ring C is 3-hydroxyproline, C 1-6 Alkyl 3-hydroxyproline ester, or C 1-6 Compounds of formula Ie-3, which are haloalkyl 3-hydroxyproline esters, are provided.

[0248] In some embodiments, the present disclosure provides compounds of formula Ie-3: Each R 6 are independently fluoro, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, =CH2, =O, tetrazolyl, imidazolyl, thiophenyl, 1,2,4-oxadiazol-3(2H)-onyl, morpholinyl, phenyl, -(CH2) 1-4 OC 1-4Alkyl, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(CH2) 0-4CHCHCO2H, -(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Haloalkyl, -OCOC 1-4 Alkyl, -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, -(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, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolid-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, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2)0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2, -(CH2) 0-4 CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(CH2) 0-4 N[(CH2) 1-4 CO2C 1-4 alkyl]2, -(CH2) 0-4 NR aCO(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, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4.

[0249] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Compounds of formula Ie-3 are provided in which m is haloalkyl, or —OH, and m is 1, 2 or 3, particularly 1 or 2.

[0250] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -methoxy, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Compounds of formula Ie-3 are provided in which m is alkyl, or —OH, and m is 1, 2 or 3, in particular 1 or 2.

[0251] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula Ie-3, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0252] In some embodiments, the present disclosure provides that ring A is [ka] and R 2 but [ka] and thereby, respectively, formula Ie-4 or formula Ie-4 * Compounds of: [ka] or a pharmaceutically acceptable salt thereof, wherein: Ring C is pyrrolyl or a 4-10 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocyclic ring having 0-3 heteroatoms (in addition to the nitrogen already shown for Ring C) independently selected from nitrogen, oxygen and sulfur; Each R 6 are independently 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 and; m is 1, 2, 3 or 4; R, R B , R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0253] In some embodiments, the present disclosure provides a compound of formula Ie-4 or Ie-4, wherein Ring C is azetidinyl, pyrrolyl, 2,3-dihydro-1H-pyrrolyl, pyrrolidinyl, piperidinyl, morpholinyl, thiazolidinyl, indolinyl, isoindolinyl, octahydroindolyl, azepanyl, oxazepane, azabicyclohexane, azabicycloheptane, azabicyclooctane, azabicyclononane, azaspiroheptane, or octahydrocyclicpentapyrrole. * The present invention provides a compound of the formula:

[0254] In certain embodiments, the present disclosure provides compounds of Formula Ie-4 or Formula Ie-4, wherein Ring C is pyrrolyl, 2-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptanyl, or octahydrocyclopenta[b]pyrrolyl. * The present invention provides a compound of the formula:

[0255] In certain embodiments, the present disclosure provides a compound in which ring C is 3-hydroxyproline, C 1-6 Alkyl 3-hydroxyproline ester, or C 1-6 Haloalkyl 3-hydroxyproline esters of formula Ie-4 or formula Ie-4 * The present invention provides a compound of the formula:

[0256] In some embodiments, the present disclosure provides a compound of formula Ie-4 or formula Ie-4 * providing a compound of the formula: Each R 6 are independently fluoro, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, =CH2, =O, tetrazolyl, imidazolyl, thiophenyl, 1,2,4-oxadiazol-3(2H)-onyl, morpholinyl, phenyl, -(CH2) 1-4 OC 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(CH2) 0-4 CHCHCO2H, -(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Haloalkyl, -OCOC 1-4 Alkyl, -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, -(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, -(CH2) 0-4 C(O)NR a (CH2) 1-4 (pyrrolid-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, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2, -(CH2) 0-4 CO(N-pyrrolidine)-(tetrazole), -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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 NRa (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(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, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4.

[0257] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4 Formula Ie-4 or Formula Ie-4, wherein m is haloalkyl or —OH and m is 1, 2 or 3, in particular 1 or 2 * The present invention provides a compound of the formula:

[0258] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -methoxy, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2)0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Formula Ie-4 or Formula Ie-4, where m is alkyl or —OH and m is 1, 2 or 3, in particular 1 or 2 * The present invention provides a compound of the formula:

[0259] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is chloro at the 7- and 8-positions relative to the quinoline ring, or formula Ie-4 * The present invention provides a compound of the formula:

[0260] In some embodiments, the present disclosure provides that ring A is [ka] and R 2 but [ka] and thereby, respectively, Formula Ie-5 or Formula Ie-5 * Compounds of: [ka] or a pharmaceutically acceptable salt thereof, wherein: Ring C is pyrrolyl or a 4-10 membered saturated or partially unsaturated monocyclic, bicyclic, bridged bicyclic or spirocyclic heterocyclic ring having 0-3 heteroatoms (in addition to the nitrogen already shown for Ring C) independently selected from nitrogen, oxygen and sulfur; Each R 6 are independently 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 and; m is 1, 2, 3 or 4; R, R B , R 3 and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0261] In some embodiments, the present disclosure provides a compound of formula Ie-5 or Ie-5, wherein Ring C is azetidinyl, pyrrolyl, 2,3-dihydro-1H-pyrrolyl, pyrrolidinyl, piperidinyl, morpholinyl, thiazolidinyl, indolinyl, isoindolinyl, octahydroindolyl, azepanyl, oxazepane, azabicyclohexane, azabicycloheptane, azabicyclooctane, azabicyclononane, azaspiroheptane, or octahydrocyclicpentapyrrole. * The present invention provides a compound of the formula:

[0262] In certain embodiments, the present disclosure provides compounds of Formula Ie-5 or Formula Ie-5, wherein Ring C is pyrrolyl, 2-azabicyclo[3.1.0]hexanyl, 3-azabicyclo[3.1.0]hexane, 5-azaspiro[2.4]heptanyl, or octahydrocyclopenta[b]pyrrolyl. * The present invention provides a compound of the formula:

[0263] In certain embodiments, the present disclosure provides a compound in which ring C is 3-hydroxyproline, C 1-6 Alkyl 3-hydroxyproline ester, or C 1-6 Haloalkyl 3-hydroxyproline esters of formula Ie-5 or formula Ie-5 * The present invention provides a compound of the formula:

[0264] In some embodiments, the present disclosure provides a compound of formula Ie-5 or Ie-5 * providing a compound of the formula: Each R 6 are independently fluoro, -CN, methyl, -C 3-6 Cycloalkyl, -CF3, -CO2H, -NH2, -OH, -OC 1-4 Alkyl, =CH2, =O, tetrazolyl, imidazolyl, thiophenyl, 1,2,4-oxadiazol-3(2H)-onyl, morpholinyl, phenyl, -(CH2) 1-4 OC 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH-(CH2) 1-4 O(CH2)1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(CH2) 0-4 CHCHCO2H, -(CH2) 0-4 CHCHCO2C 1-4 Alkyl, -CO2C 1-4 Alkyl, -CO2C 1-4 Haloalkyl, -OCOC 1-4 Alkyl, -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, -(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, -(CH2) 0-4 C(O)NR a (CH2)1-4 (pyrrolid-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, -(CH2) 0-4 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O-(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO(N-pyrrolidine)-(CH2) 0-4 SO2NH2, -(CH2) 0-4 CO(N-pyrrolidine)-(tetrazole), -(CH2)0-4 CO(N-piperidine)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-piperidine)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(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, -(CH2) 0-4 NR a SO2(CH2) 1-4 (imidazolidine-2,4-dione), -(CH2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4.

[0265] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -CO2H, -CO2C 1-4 Alkyl, -CO2C 1-4Formula Ie-5 or Formula Ie-5, wherein m is haloalkyl or —OH and m is 1, 2 or 3, in particular 1 or 2 * The present invention provides a compound of the formula:

[0266] In certain embodiments, the present disclosure provides a method for treating a pulmonary arthritis (PTA) comprising administering to a patient ... 6 are independently fluoro, -methyl, cyclohexyl, -CF3, -methoxy, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Formula Ie-5 or Formula Ie-5, where m is alkyl or —OH and m is 1, 2 or 3, in particular 1 or 2 * The present invention provides a compound of the formula:

[0267] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7- and 8-positions relative to the quinoline ring; or * The present invention provides a compound of the formula:

[0268] In some embodiments, the present disclosure provides that ring A is [ka] and R 2 but [ka] and thereby forming a compound of formula If-1: [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 6 are independently 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 and; m is 0, 1, 2, 3 or 4, in particular 1, 2, 3 or 4; R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0269] In some embodiments, the present disclosure provides R 6 R B The present invention provides a compound of formula If-1, wherein:

[0270] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula If-1, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0271] In certain embodiments, the present disclosure provides a compound of formula If-1: Each R 6 are independently halogen, -C 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; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0272] In certain embodiments, the present disclosure provides a compound of formula If-1: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 CO2C1-4 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 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 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) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0273] In further particular embodiments, the present disclosure provides compounds of formula If-1: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(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) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 alkyl)-CO2H, -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 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 NR a SO2C 1-4 Alkyl, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR aSO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2, or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0274] In certain embodiments, the present disclosure provides a compound of formula If-1: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(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 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 1-4 Alkyl, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0275] In further particular embodiments, the present disclosure provides compounds of formula If-1: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0276] In further specific embodiments, the present disclosure provides that each R 6 are independently fluoro, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Compounds of formula If-1 are provided wherein m is alkyl, or —OH, and m is 1, 2 or 3, particularly 1 or 2.

[0277] In certain embodiments, the present disclosure provides a compound of formula If-1: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 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 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), -OH, -(CH) 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 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0278] In further particular embodiments, the present disclosure provides compounds of formula If-1: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 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 NR 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, or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0279] In certain embodiments, the present disclosure provides a compound of formula If-3: Each R 6 are independently 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; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0280] In certain embodiments, the present disclosure provides a compound of formula If-1: Each R 6 are independently halogen, =O, -(CH2) 0-4 CO2H, -(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 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), -OH, -(CH) 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 NR a C(O)C 1-4Alkyl, -(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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0281] In further particular embodiments, the present disclosure provides compounds of formula If-1: Each R 6 are independently halogen, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-proline), -(CH2) 0-4 CO(N-pyrrolidine-3-carboxylic acid), -(CH2) 0-4 C(O)NRa (CH2) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 alkyl)-CO2H, -OH, -(CH2) 1-4 OH, -(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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0282] In certain embodiments, the present disclosure provides a compound of formula If-1: m is 1; R 6 is -(CH2) 0-4 O(CH2) 1-5 CO2H, for example, -(CH2), including -CH2O(CH2)2CO2H 1-2 O(CH2)2-3 CO2H; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0283] In certain embodiments, for the above-disclosed compounds of formula If-1, m is 1 or 2 and at least one R 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0284] In some embodiments, the present disclosure provides that ring A is [ka] and R 2 but [ka] and thereby forming a compound of formula If-2: [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 6 are independently 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 and; m is 0, 1, 2, 3 or 4, in particular 1, 2, 3 or 4; R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0285] In some embodiments, the present disclosure provides R 6 R B provides a compound of formula If-2, wherein:

[0286] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula If-2, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0287] In certain embodiments, the present disclosure provides a compound of formula If-2: Each R 6 are independently halogen, -C 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; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0288] In certain embodiments, the present disclosure provides a compound of formula If-2: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(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 (N-pyrazole)-(CH2) 0-4CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 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) 1-4 O(CH2) 1-4CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl, -(CH2) 0-4 NR a C(O)C 1-4Alkyl, -(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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0289] In further specific embodiments, the present disclosure provides compounds of formula If-2: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(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) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 alkyl)-CO2H, -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 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0290] In certain embodiments, the present disclosure provides a compound of formula If-2: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(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 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 1-4 Alkyl, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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) 0-4 NR a SO2C 1-4 Alkyl, -(CH2) 0-4 NRa 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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0291] In certain embodiments, the present disclosure provides a compound of formula If-2: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2)1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(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 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 1-4 Alkyl, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4 Alkyl, -(CH2) 0-4 NR a C(O)C1-4 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0292] In further specific embodiments, the present disclosure provides compounds of formula If-2: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2)0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0293] In further specific embodiments, the present disclosure provides that each R 6 are independently fluoro, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Compounds of formula If-2 are provided in which m is alkyl, or —OH, and m is 1, 2 or 3, in particular 1 or 2.

[0294] In certain embodiments, the present disclosure provides a compound of formula If-2: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 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 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), -OH, -(CH) 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 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0295] In further specific embodiments, the present disclosure provides compounds of formula If-2: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0296] In certain embodiments, the present disclosure provides a compound of formula If-2: Each R 6 are independently 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; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0297] In certain embodiments, the present disclosure provides a compound of formula If-2: Each R 6 are independently halogen, =O, -(CH2) 0-4 CO2H, -(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 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), -OH, -(CH) 1-4 OH, -(CH2) 0-4 OC 1-4Alkyl, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0298] In further specific embodiments, the present disclosure provides compounds of formula If-2: Each R 6are independently halogen, -(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)-CO2H, -OH, -(CH2) 1-4 OH, -(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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0299] In certain embodiments, the present disclosure provides a compound of formula If-2: m is 1; R 6 is -(CH2) 0-4 O(CH2) 1-5 CO2H, for example, -(CH2), including -CH2O(CH2)2CO2H 1-2 O(CH2) 2-3 CO2H; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0300] In certain embodiments, for the above-disclosed compounds of formula If-2, m is 1 or 2 and at least one R 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0301] In some embodiments, the present disclosure provides that ring A is [ka] and R 2 but [ka] and thereby forming a compound of formula If-3: [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 6 are independently 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 and; m is 0, 1, 2, 3 or 4, in particular 1, 2, 3 or 4; R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0302] In some embodiments, the present disclosure provides R 6 R B provides a compound of formula If-3, wherein:

[0303] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 provides compounds of formula If-3, which are chloro at the 7 and 8 positions relative to the quinoline ring.

[0304] In certain embodiments, the present disclosure provides a compound of formula If-3: Each R 6 are independently halogen, -C 1-4 Alkyl, -C1-4 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; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0305] In certain embodiments, the present disclosure provides a compound of formula If-3: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(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(C1-4 alkyl)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, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 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) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0306] In further particular embodiments, the present disclosure provides compounds of formula If-3: Each R 6are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(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) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 alkyl)-CO2H, -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 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0307] In certain embodiments, the present disclosure provides a compound of formula If-3: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(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 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4-O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 1-4 Alkyl, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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 C1-4 Alkyl, -(CH2) 0-4 NR a SO2C 1-4 Alkyl, -(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), or CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0308] In further particular embodiments, the present disclosure provides compounds of formula If-3: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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)NRa -CH(C 1-4 alkyl)-CO2H, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0309] In further specific embodiments, the present disclosure provides that each R 6 are independently fluoro, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2)0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Compounds of formula If-3 are provided in which m is alkyl, or —OH, and m is 1, 2 or 3, particularly 1 or 2.

[0310] In certain embodiments, the present disclosure provides a compound of formula If-3: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 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 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(C1-4 alkyl), -OH, -(CH) 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 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0311] In further particular embodiments, the present disclosure provides compounds of formula If-3: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 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 NR a SO2C 1-4 Alkyl, -(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, R ais independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0312] In certain embodiments, the present disclosure provides a compound of formula If-3: Each R 6 are independently 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; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0313] In certain embodiments, the present disclosure provides a compound of formula If-3: Each R 6 are independently halogen, =O, -(CH2) 0-4 CO2H, -(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 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), -OH, -(CH) 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 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 1-4alkyl)2, -(CH2) 0-4 SO3H, -(CH2) 0-4 SO2NH2, -(CH2) 0-4 SO2NR a C 1-4 Alkyl, -(CH2) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0314] In further particular embodiments, the present disclosure provides compounds of formula If-3: Each R 6 are independently halogen, -(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)-CO2H, -OH, -(CH2) 1-4 OH, -(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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0315] In certain embodiments, the present disclosure provides a compound of formula If-3: m is 1; R 6 is -(CH2) 0-4 O(CH2) 1-5 CO2H, for example, -(CH2), including -CH2O(CH2)2CO2H 1-2 O(CH2) 2-3 CO2H; Each R 3 are independently optionally substituted C 1-6aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0316] In certain embodiments, for the above-disclosed compounds of formula If-3, m is 1 or 2 and at least one R 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0317] In some embodiments, the present disclosure provides that ring A is [ka] and R 2 but [ka] and thus, formula If-4 or formula If-4 * Compounds of: [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 6 are independently 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 and; m is 0, 1, 2, 3 or 4, in particular 1, 2, 3 or 4; R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0318] In some embodiments, the present disclosure provides R 6 R B Not Expression If-4 or Expression If-4 * The present invention provides a compound of the formula:

[0319] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a compound of formula If-4 or formula If-4, in which chloro is at the 7th and 8th positions relative to the quinoline ring * The present invention provides a compound of the formula:

[0320] In certain embodiments, the present disclosure provides a compound of formula If-4 or formula If-4 * providing a compound of the formula: Each R 6 are independently halogen, -C 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; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0321] In certain embodiments, the present disclosure provides a compound of formula If-4 or formula If-4 * providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(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 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 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 1-4Alkyl, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0322] In further specific embodiments, the present disclosure provides a compound of formula If-4 or formula If-4 * providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4Haloalkyl, =CH2, -(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) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 alkyl)-CO2H, -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 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0323] In certain embodiments, the present disclosure provides a compound of formula If-4 or formula If-4 * providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(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 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C1-4 Alkyl, -(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), -OH, -(CH) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 1-4 Alkyl, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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) 0-4 NRa SO2C 1-4 Alkyl, -(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), or CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0324] In further specific embodiments, the present disclosure provides a compound of formula If-4 or formula If-4 * providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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(C1-4 alkyl)-CO2H, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0325] In further specific embodiments, the present disclosure provides that each R 6 are independently fluoro, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2)1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Formula If-4 or Formula If-4, where m is alkyl or -OH and m is 1, 2 or 3, in particular 1 or 2 * The present invention provides a compound of the formula:

[0326] In certain embodiments, the present disclosure provides a compound of formula If-4 or formula If-4 * providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 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 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), -OH, -(CH) 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 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0327] In further specific embodiments, the present disclosure provides a compound of formula If-4 or formula If-4 * providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 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 NR a SO2C 1-4 Alkyl, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2, or -(CR2) 0-4OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0328] In certain embodiments, the present disclosure provides a compound of formula If-4 or formula If-4 * providing a compound of the formula: Each R 6 are independently 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; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0329] In certain embodiments, the present disclosure provides a compound of formula If-4 or formula If-4 * providing a compound of the formula: Each R 6 are independently halogen, =O, -(CH2) 0-4 CO2H, -(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 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), -OH, -(CH) 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 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0330] In further specific embodiments, the present disclosure provides a compound of formula If-4 or formula If-4 * providing a compound of the formula: Each R 6 are independently halogen, -(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) 1-4CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 alkyl)-CO2H, -OH, -(CH2) 1-4 OH, -(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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0331] In certain embodiments, the present disclosure provides a compound of formula If-4 or formula If-4 * providing a compound of the formula: m is 1; R 6 is -(CH2) 0-4 O(CH2) 1-5 CO2H, for example, -(CH2), including -CH2O(CH2)2CO2H 1-2 O(CH2)2-3 CO2H; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0332] In certain embodiments, formula If-4 or formula If-4 * For the above disclosed compounds of 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0333] In some embodiments, the present disclosure provides that ring A is [ka] and R 2 but [ka] and so that equations If-5 and If-5 respectively * Compounds of: [ka] or a pharmaceutically acceptable salt thereof, wherein: Each R 6 are independently 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 and; m is 0, 1, 2, 3 or 4, in particular 1, 2, 3 or 4; R, R 3 , R B and n, alone and in combination, are each as defined above and described in the embodiments herein.

[0334] In some embodiments, the present disclosure provides R 6 R B Not Expression If-5 or Expression If-5 * The present invention provides a compound of the formula:

[0335] In certain embodiments, the present disclosure provides R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a compound of formula If-5 or formula If-5, in which chloro is at the 7th and 8th positions relative to the quinoline ring * The present invention provides a compound of the formula:

[0336] In certain embodiments, the present disclosure provides a compound of formula If-5 or formula If-5 * providing a compound of the formula: Each R 6 are independently halogen, -C 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; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0337] In certain embodiments, the present disclosure provides a compound of formula If-5 or formula If-5 * providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, =O, -(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) 0-4CON(C 1-4 alkyl)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, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 1-4 OH, -(CH2) 0-4 OC 1-4Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C 1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2)1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0338] In further specific embodiments, the present disclosure provides a compound of formula If-5 or formula If-5* providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, =CH2, -(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) 1-4 CO2H, -(CH2) 0-4 C(O)NR a -CH(C 1-4 alkyl)-CO2H, -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 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 NR a SO2C 1-4 Alkyl, -(CH2) 0-4 NR a SO2Ph, -(CH2) 0-4 NR a SO2(CH2) 1-4 CO2H, -(CH2) 0-4 OP(OH)2, or -(CR2) 0-4OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0339] In certain embodiments, the present disclosure provides a compound of formula If-5 or formula If-5 * providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 1-4 Alkyl, -(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, -(CH2) 1-4 O(CH2) 1-4 CHFCO2H, -(CH2) 1-4 O(CH2) 1-4 CHFCO2C 1-4 Alkyl, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2H, -(CH2) 1-4 OCH(CH3)(CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2H, -(CH2) 1-4 O(CH2) 1-4 CH(CH3)CO2C1-4 Alkyl, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2H, -CHOH(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -CHCF3(CH2) 1-4 O(CH2) 1-5 CO2H, -CHCF3(CH2) 1-4 O-(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -(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 (N-pyrazole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrazole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 (N-Pyrrole)-(CH2) 0-4 CO2H, -(CH2) 0-4 CO(N-pyrrole)-(CH2) 0-4 CO2C 1-4 Alkyl, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(phenyl)-(CH2) 0-4 CO2C 1-4Alkyl, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2H, -(CH2) 0-4 -O(cycloalkane)-(CH2) 0-4 CO2C 1-4 Alkyl, -(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), -OH, -(CH) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 1-4 Alkyl, -NH2, -(CH2) 0-4 NR a (CH2) 1-4 CO2H, -(CH2) 0-4 NR a (CH2) 1-4 CO2C 1-4 Alkyl, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 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) 0-4SO3H, -(CH2) 0-4 SO2NH2, -(CH2) 0-4 SO2NR a C 1-4 Alkyl, -(CH2) 0-4 NR a SO2C 1-4 Alkyl, -(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), or CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0340] In further specific embodiments, the present disclosure provides a compound of formula If-5 or formula If-5 * providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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)-CO2H, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -(CH2) 0-4 OC(O)C 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0341] In further specific embodiments, the present disclosure provides that each R 6are independently fluoro, -methyl, cyclohexyl, -methoxy, -OtBu, -CF3, -(CH2) 1-5 CO2H, -(CH2) 1-5 CO2C 1-4 Alkyl, -(CH2) 0-4 O(CH2) 1-5 CO2H, -(CH2) 0-4 O(CH2) 1-5 CO2C 1-4 Formula If-5 or Formula If-5, where m is alkyl or —OH and m is 1, 2 or 3, in particular 1 or 2 * The present invention provides a compound of the formula:

[0342] In certain embodiments, the present disclosure provides a compound of formula If-5 or If-5 * providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, =O, -(CH2) 0-4 CO2H, -(CH2) 0-4 CO2C 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 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), -OH, -(CH) 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 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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0343] In further specific embodiments, the present disclosure provides a compound of formula If-5 or formula If-5 * providing a compound of the formula: Each R 6 are independently halogen, -C 1-4 Alkyl, -C 1-4 Haloalkyl, -C 3-6 Cycloalkyl, =CH2, -(CH2) 0-4 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2H, -(CH2) 1-4 O(CH2) 1-5 CO2C 1-4 Alkyl, -(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, -OH, -(CH2) 1-4 OH, -(CH2) 0-4 OC 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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0344] In certain embodiments, the present disclosure provides a compound of formula If-5 or formula If-5 * providing a compound of the formula: Each R 6 are independently 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; m is 1, 2, 3 or 4, in particular 1 or 2; Each R3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0345] In certain embodiments, the present disclosure provides a compound of formula If-5 or formula If-5 * providing a compound of the formula: Each R 6 are independently halogen, =O, -(CH2) 0-4 CO2H, -(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 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), -OH, -(CH) 1-4 OH, -(CH2) 0-4 OC 1-4 Alkyl, -NH2, -(CH2) 1-4 NH2, -(CH2) 0-4 NHC 1-4Alkyl, -(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) 0-4 NR a SO2C 1-4 Alkyl, -(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), or -(CR2) 0-4 OP(O)(H)OH, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1, 2, 3 or 4, in particular 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0346] In further specific embodiments, the present disclosure provides a compound of formula If-5 or formula If-5 * providing a compound of the formula: Each R 6 are independently halogen, -(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)-CO2H, -OH, -(CH2) 1-4 OH, -(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 NR a SO2C 1-4 Alkyl, -(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, R a is independently for each occurrence H, or C 1-4 is alkyl; m is 1 or 2; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0347] In certain embodiments, the present disclosure provides a compound of formula If-5 or formula If-5 * providing a compound of the formula: m is 1; R 6 is -(CH2) 0-4 O(CH2) 1-5 CO2H, for example, -(CH2), including -CH2O(CH2)2CO2H 1-2 O(CH2) 2-3 CO2H; Each R 3 are independently optionally substituted C 1-6 aliphatic, e.g., methyl, or halogen, e.g., bromo and / or chloro, e.g., dichloro, e.g., n is 2 and R 3 is a chloro at the 7 and 8 positions relative to the quinoline ring.

[0348] In certain embodiments, formula If-5 or formula If-5 * For the above disclosed compounds of 6 contains a terminal -COH group. For example, in certain cases, at least one R 6 is -(CH2) 0-4 CO2H, or -(CH2) 0-4 O(CH2) 1-5 CO2H.

[0349] As defined above and described herein, each R is independently hydrogen or C 1-6 benzyl; phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; and a 5- to 6-membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur, or two R groups on the same nitrogen, optionally taken together with their intervening atoms, form an optionally substituted 4- to 7-membered saturated, partially unsaturated, or heteroaryl ring having, in addition to the nitrogen, 0-3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur.

[0350] In some embodiments, R is hydrogen. In some embodiments, R is an optionally substituted C 1-6 It is aliphatic. In some embodiments, R is optionally substituted benzyl. In some embodiments, R is optionally substituted phenyl. In some embodiments, R is an optionally substituted 4-10-membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur. In some embodiments, R is an optionally substituted 5-6-membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur. In some embodiments, two R groups on the same nitrogen, optionally together with their intervening atoms, form an optionally substituted 4-7-membered saturated, partially unsaturated, or heteroaryl ring having, in addition to the nitrogen, 0-3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur.

[0351] In some embodiments, two R groups on the same carbon atom (e.g., -(CR2)-, etc.) optionally taken together with their intervening atoms form an optionally substituted 4-7 membered saturated or partially unsaturated ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur.

[0352] In some embodiments, two R groups on different atoms (e.g., -P(O)(OR)2, -B(OR)2, etc.) are optionally joined together with their intervening atoms to form an optionally substituted 4-7 membered saturated or partially unsaturated ring having 0-3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur.

[0353] 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) 1-5In some embodiments, R is —(CH) 1-5 CO2C 1-4 It is alkyl.

[0354] In some embodiments, R is selected from the groups shown in Table 1.

[0355] In some embodiments, R is selected from the groups shown in Table 2.

[0356] In some embodiments, R 2 is R B and R B may be substituted C 1-6 Aliphatic, preferably substituted C 1-6 Aliphatic, e.g., (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), especially -(CR) 1-4 NR(CR2) 0-6 CO2R, or -(CR2) 1-4 COR. In some embodiments, R 2 is -(CH2) 1-4 NR a (CH2) 0-4 CO2R a , for example, -(CH2) 1-4 NR a (CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CH2) 1-4 N(SO2C 1-4alkyl)(CH2) 0-4 CO2R a , for example, -(CH2) 1-4 N(SO2C 1-4 alkyl)(CH2) 0-4 CO2H and R a is independently for each occurrence H, or C 1-4 In another embodiment, R 2 is -(CR2) 1-4 CO2R, e.g., -(CH2) 1-4 Contains CO2H-(CR2) 1-4 In certain embodiments, R 2 contains a terminal -COH group. For example, in certain cases, R 2 is the terminal -(CH2) 0-4 Contains CO2H groups.

[0357] R, as defined above and described herein 2 is halogen, -OR, -NR2, -NRC(O)OR, -NRC(O)R, -NRC(O)NR2, -NRSO2R, -SR, -S2R, -SO2NR2, -S(O)R, or R B , especially -NR2, or R B is 。

[0358] In some embodiments, R 2 is a halogen. In some embodiments, R 2 is -OR. In some embodiments, R 2 In some embodiments, R is -NR. In some embodiments, R is -NRC(O)OR. In some embodiments, R 2 is -NRC(O)R. In some embodiments, R 2 is -NRC(O)NR. In some embodiments, R 2 is -NRSO2R, -SR. In some embodiments, R 2 is -SO2R. In some embodiments, R 2 is -SO2NR2. In some embodiments, R 2is -S(O)R. In some embodiments, R 2 is R B is.

[0359] In some embodiments, R 2 is hydrogen. In some embodiments, R 2 is chloro. In some embodiments, R 2 is methyl. In some embodiments, R 2 is —CF. In some embodiments, R 2 is phenyl. In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] is.

[0360] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] In some embodiments, R 2 teeth [ka] ...

Claims

1. Of formula I: 【Chemistry 1】 (In the formula: Ring A is an optionally substituted group selected from HetAr and HetCy; HetAr is a 5-6 membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and said 5-6 membered heteroaryl ring is not imidazole or pyrazole; HetCy is a 4-7 membered saturated or partially unsaturated heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; R ２ but, 【Chemistry 2】 and Each R ３ are independently halogen, —OR, —NR ２ , -SR, or R Ｃ and at least one occurrence of R 3 is halogen; Ring B1 is phenyl, preferably substituted 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, 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 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 C １－６ benzyl; phenyl; a 4- to 10-membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; and a 5- to 6-membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur, or an optionally substituted group selected from: two R groups on the same nitrogen, optionally taken together with their intervening atoms, form an optionally substituted 4-7 membered saturated, partially unsaturated, or heteroaryl ring having, in addition to said nitrogen, 0-3 heteroatoms independently selected from nitrogen, oxygen, phosphorus, and sulfur; Each R ６ are independently halogen, -COR, -(CR ２ ) ０－４ CO ２ R, -(CR ２ ) ０－４ CONR ２ , -OR, -(CR ２ ) １－４ OR, -NR ２ , -(CR ２ ) １－４ NR ２ , -NRC(O)OR, -NRC(O)R, -NRC(O)NR ２ , -SR, -SO ２ R, -S(O)R, -(CR ２ ) ０－４ SO ３ R, -(CR ２ ) ０－４ SO ２ NR ２ , -(CR ２ ) ０－４ OSO ２ NR ２ , -(CR ２ ) ０－４ NRSO ２ R, -(CR ２ ) ０－４ NRSO ２ OR, -(CR ２ ) ０－４ OP (OR) ２ , -(CR ２ ) ０－４ OP (O) (OR) ２ , -(CR ２ ) ０－４ P(O)(OR) ２ , -(CR ２ ) ０－４ OP(O)(H)OR, -B(OR) ２ , or R Ｂ and R Ｂ and R Ｃ But independently, C １－６ an optionally substituted group selected from aliphatic; phenyl; a 4-10 membered saturated or partially unsaturated monocyclic or bicyclic carbocyclic or heterocyclic ring having 1-3 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and a 5-6 membered heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur; Each R ａ are independently H, or C １－６ is alkyl; each m is 1, 2, 3, or 4; n is 1, 2, 3 or 4; q is 0, 1 or 2; However, the compound is one of the following: 【Transformation 3】 isn't it) or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein ring A is an optionally substituted HetCy.

3. The compound of claim 1 , wherein ring A is optionally substituted HetAr.

4. Ring A is 【Transformation 5】 2. The compound of claim 1 selected from:

5. Ring A is 【Transformation 6】 2. The compound of claim 1 selected from:

6. Formulas I-d-1 to I-d-5 ＊ : 【Transformation 7】 10. The compound of claim 1, wherein the compound is one of:

7. R ３ 2. The compound of claim 1, wherein at least one occurrence of is chloro.

8. R ３ 2. The compound of claim 1, wherein at least one occurrence of is bromo.

9. n is 2, and both R ３ The compound of claim 1 , wherein is chloro.

10. n is 2 and R ３ is chloro at the 7 and 8 positions relative to the quinoline ring.

11. R ２ but 【Transformation 8】 2. The compound of claim 1, wherein:

12. 12. The compound of claim 11, wherein Ring B1 is a substituted phenyl.

13. 13. The compound of claim 12, wherein the phenyl is substituted with one or more carboxyl groups.

14. Ring B1 is one or more R ６ The compound according to claim 12, which is a 3-carboxyphenyl group optionally substituted by a group.

15. Ring B1 is one or more R ６ The compound according to claim 12, which is a 3,5-dicarboxyphenyl group optionally substituted by a group.

16. 12. The compound of claim 11, 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.

17. 12. The compound of claim 11, wherein ring B1 is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

18. R ２ but 【Chemistry 9】 where: X is either absent (i.e., a bond within the ring) or -CR ２ -, -NR-, -O-, -S-, or -SO ２ - and; 2. The compound of claim 1, wherein p is 0, 1, or 2.

19. X is -CR ２ The compound of claim 18, wherein the aryl group is -, -NR-, or -O-.

20. 19. The compound of claim 18, wherein p is 1.

21. Each R ６ are independently halogen, ═CH ２ , =O, -C １－４ Alkyl, -C １－４ Haloalkyl, -(CH ２ ) ０－４ CO ２ H, -(CH ２ ) ０－４ CO ２ C １－４ Alkyl, -(CH ２ ) ０－４ CO ２ C １－４ Haloalkyl, -(CH ２ ) ０－４ CONH ２ , -(CH ２ ) ０－４ CONHC １－４ Alkyl, -(CH ２ ) ０－４ CON (C １－４ alkyl) ２ , -(CH ２ ) ０－４ CO(N-proline), -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CO ２ H, -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CONH ２ , -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CONHC １－４ Alkyl, -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CON (C １－４ alkyl) ２ , -OH, -(CH ２ ) １－４ OH, -(CH ２ ) ０－４ O.C. １－４ Alkyl, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ H, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ C １－４ Alkyl, -(CH ２ ) ０－４ O.C.(O.C.) １－４ Alkyl, —NH ２ , -(CH ２ ) １－４ NH ２ , -(CH ２ ) ０－４ NHC １－４ Alkyl, -(CH ２ ) ０－４ N (C １－４ alkyl) ２ , -(CH ２ ) ０－４ SO ３ H, -(CH ２ ) ０－４ SO ２ NH ２ , -(CH ２ ) ０－４ SO ２ NHC １－４ Alkyl, -(CH ２ ) ０－４ NR ａ SO ２ C １－４ Alkyl, -(CH ２ ) ０－４ OP (OH) ２ , -(CH ２ ) ０－４ OP(OH)(OC １－４ alkyl), or -(CR ２ ) ０－４ OP(O)(H)OH, and R ａ is, independently for each occurrence, H, or C １－４ The compound of claim 11 , wherein the compound is alkyl.

22. Each R ６ are independently halogen, ═CH ２ , =O, -C １－４ Alkyl, -C １－４ Haloalkyl, -(CH ２ ) ０－４ CO ２ H, -(CH ２ ) ０－４ CO ２ C １－４ Alkyl, -(CH ２ ) ０－４ CO(N-proline), -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CO ２ H, -OH, -(CH ２ ) １－２ OH, -(CH ２ ) ０－４ O.C. １－４ Alkyl, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ H, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ C １－４ Alkyl, -(CH ２ ) ０－４ O.C.(O.C.) １－４ Alkyl, -(CH ２ ) ０－４ SO ３ H, -(CH ２ ) ０－４ SO ２ NH ２ , -(CH ２ ) ０－４ NR ａ SO ２ C １－４ Alkyl, -(CH ２ ) ０－４ OP (OH) ２ , or -(CR ２ ) ０－４ 12. The compound of claim 11, which is OP(O)(H)OH.

23. Each R ６ are independently halogen, ═CH ２ , =O, -C １－４ Alkyl, -C １－４ Haloalkyl, -(CH ２ ) ０－２ CO ２ H, -(CH ２ ) ０－２ CO ２ C １－４ Alkyl, -(CH ２ ) １－４ CO(N-proline), -(CH ２ ) ０－２ C(O)NR ａ (CH ２ ) １－４ CO ２ H, -OH, -(CH ２ ) １－２ OH, -(CH ２ ) ０－２ O.C. １－４ Alkyl, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ H, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ C １－４ Alkyl, -(CH ２ ) ０－２ O.C.(O.C.) １－４ Alkyl, -(CH ２ ) ０－２ SO ３ H, -(CH ２ ) ０－２ SO ２ NH ２ , -(CH ２ ) ０－２ NR ａ SO ２ C ０－２ Alkyl, -(CH ２ ) ０－２ OP (OH) ２ , or -(CR ２ ) ０－２ 12. The compound of claim 11, which is OP(O)(H)OH.

24. Each R ６ are independently halogen, ═CH ２ , =O, -C １－４ Alkyl, -C １－４ Haloalkyl, —CO ２ H, -CO ２ C １－４ Alkyl, —CO(N-proline), —CH ２ CO ２ H, —OH, —OC １－４ Alkyl, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ H, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ C １－４ Alkyl, —OC(O)C １－４ Alkyl, —SO ３ H, -SO ２ NH ２ , -NR ａ SO ２ C １－４ Alkyl, -OP(OH) ２ or -OP(O)(H)OH.

25. R ２ but 【Chemistry 10】 2. The compound of claim 1, wherein:

26. 26. The compound of claim 25, wherein m is 1 or 2.

27. R ２ but 【Chemistry 11】 2. The compound of claim 1, wherein:

28. 28. The compound of claim 27, wherein m is 1 or 2.

29. Each R ６ are independently halogen, ═CH ２ , -C １－４ Alkyl, -C １－４ Haloalkyl, -(CH ２ ) ０－４ CO ２ H, -(CH ２ ) ０－４ CO ２ C １－４ Alkyl, -(CH ２ ) ０－４ CO ２ C １－４ Haloalkyl, -(CH ２ ) ０－４ CONH ２ , -(CH ２ ) ０－４ CONHC １－４ Alkyl, -(CH ２ ) ０－４ CON (C １－４ alkyl) ２ , -(CH ２ ) ０－４ CO(N-proline), -(CH ２ ) ０－４ CO(N-pyrrolidine-3-carboxylic acid), -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CO ２ H, -(CH ２ ) ０－４ C(O)NR ａ -CH(C １－４ alkyl)-CO ２ H, -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CONH ２ , -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CONHC １－４ Alkyl, -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CON (C １－４ alkyl) ２ , -OH, -(CH ２ ) １－４ OH, -(CH ２ ) ０－４ O.C. １－４ Alkyl, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ H, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ C １－４ Alkyl, -(CH ２ ) ０－４ O.C.(O.C.) １－４ Alkyl, —NH ２ , -(CH ２ ) １－４ NH ２ , -(CH ２ ) ０－４ NHC １－４ Alkyl, -(CH ２ ) ０－４ NR ａ C(O)C １－４ Alkyl, -(CH ２ ) ０－４ NR ａ C(O)Ph, -(CH ２ ) ０－４ NR ａ CO(CH ２ ) １－４ OH, -(CH ２ ) ０－４ N (C １－４ alkyl) ２ , -(CH ２ ) ０－４ SO ３ H, -(CH ２ ) ０－４ SO ２ NH ２ , -(CH ２ ) ０－４ SO ２ NR ａ C １－４ Alkyl, -(CH ２ ) ０－４ NR ａ SO ２ C １－４ Alkyl, -(CH ２ ) ０－４ NR ａ SO ２ Ph, -(CH ２ ) ０－４ NR ａ SO ２ (CH ２ ) １－４ CO ２ H, -(CH ２ ) ０－４ OP (OH) ２ , -(CH ２ ) ０－４ OP(OH)(OC １－４ alkyl), or -(CR ２ ) ０－４ OP(O)(H)OH, and R ａ is, independently for each occurrence, H, or C １－６ 26. The compound of claim 25, wherein the compound is alkyl.

30. Each R ６ are independently halogen, ═CH ２ , =O, -C １－４ Alkyl, -C １－４ Haloalkyl, —CO ２ H, -(CH ２ ) ０－４ CO ２ H, -(CH ２ ) ０－４ CO ２ C １－４ Alkyl, -(CH ２ ) ０－４ CO ２ C １－４ Haloalkyl, -(CH ２ ) ０－４ CO(N-proline), -(CH ２ ) ０－４ CO(N-pyrrolidine-3-carboxylic acid), -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CO ２ H, -(CH ２ ) ０－４ C(O)NR ａ -CH(C １－４ alkyl)-CO ２ H, -OH, -(CH ２ ) １－４ OH, -OC １－４ Alkyl, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ H, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ C １－４ Alkyl, -(CH ２ ) ０－４ NR ａ C(O)C １－４ Alkyl, -(CH ２ ) ０－４ NR ａ C(O)Ph, -(CH ２ ) ０－４ NR ａ CO(CH ２ ) １－４ OH, -(CH ２ ) ０－４ SO ３ H, -(CH ２ ) ０－４ SO ２ NH ２ , -(CH ２ ) ０－４ NR ａ SO ２ C １－４ Alkyl, -(CH ２ ) ０－４ NR ａ SO ２ Ph, - (CH ２ ) ０－４ NR ａ SO ２ (CH ２ ) １－４ CO ２ H, -(CH ２ ) ０－４ OP (OH) ２ , or -(CR ２ ) ０－４ OP(O)(H)OH, and R ａ is, independently for each occurrence, H, or C １－４ 26. The compound of any one of claims 25, which is alkyl.

31. Each R ６ are independently halogen, ═CH ２ , =O, -C １－４ Alkyl, -C １－４ Haloalkyl, —CO ２ H, -CO ２ C １－４ Alkyl, —CO ２ C １－４ Haloalkyl, —CO(N-proline), —CO(N-pyrrolidine-3-carboxylic acid), —C(O)NR ａ (CH ２ ) １－４ CO ２ H, —C(O)NR ａ -CH(C １－４ alkyl)-CO ２ H, —OH, —OC １－４ Alkyl, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ H, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ C １－４ Alkyl, —NR ａ C(O)C １－４ Alkyl, —NR ａ C(O)Ph, -NR ａ CO(CH ２ ) １－４ OH, -SO ３ H, -SO ２ NH ２ , -NR ａ SO ２ C １－４ Alkyl, —NR ａ SO ２ Ph, -NR ａ SO ２ (CH ２ ) １－４ CO ２ H, -OP(OH) ２ or —OP(O)(H)OH, and R ａ is, independently for each occurrence, H, or C １－４ 26. The compound of claim 25, wherein the compound is alkyl.

32. The compound according to claim 17, wherein ring B1 is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and a carbon atom of the 5- to 6-membered heteroaryl ring is directly bonded to the carbon atom at position 2 of the quinolone ring;

33. 18. The compound of claim 17, wherein Ring B1 is imidazole or pyrazole.

34. R ２ but 【Chemistry 14】 2. The compound of claim 1, wherein:

35. 35. The compound of claim 34, 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.

36. 35. The compound of claim 34, wherein ring B2 is a 5- to 6-membered heteroaryl ring having 1 to 4 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

37. R ２ but, 【Chemistry 15】 where: X is either absent (i.e., a bond within the ring) or -CR ２ -, -NR-, -O-, -S-, or -SO ２ - and; 35. The compound of claim 34, wherein m is 1, 2, 3, or 4.

38. X is -CR ２ 38. The compound of claim 37, wherein the aryl group is -, -NR-, or -O-.

39. 38. The compound of claim 37, wherein q is 1 or 2.

40. 38. The compound of claim 37, wherein q is 1.

41. 38. The compound of claim 37, wherein m is 1 or 2.

42. Each R ６ are independently halogen, -(CH ２ ) ０－４ CO ２ H, -(CH ２ ) ０－４ CO ２ C １－４ Alkyl, -(CH ２ ) ０－４ CONH ２ , -(CH ２ ) ０－４ CONHC １－４ Alkyl, -(CH ２ ) ０－４ CON (C １－４ alkyl) ２ , - (CH ２ ) ０－４ CO(N-proline), -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CO ２ H, -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CONH ２ , -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CONHC １－４ Alkyl, -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CON (C １－４ alkyl) ２ , -OH, -(CH ２ ) １－４ OH, -(CH ２ ) ０－４ O.C. １－４ Alkyl, —NH ２ , -(CH ２ ) １－４ NH ２ , -(CH ２ ) ０－４ NHC １－４ Alkyl, -(CH ２ ) ０－４ N (C １－４ alkyl) ２ , -(CH ２ ) ０－４ SO ３ H, -(CH ２ ) ０－４ SO ２ NH ２ , -(CH ２ ) ０－４ SO ２ NHC １－４ Alkyl, -(CH ２ ) ０－４ NR ａ SO ２ C １－４ Alkyl, -(CH ２ ) ０－４ OP (OH) ２ , -(CH ２ ) ０－４ OP(OH)(OC １－４ alkyl), or -(CR ２ ) ０－４ OP(O)(H)OH, and R ａ is, independently for each occurrence, H, or C １－４ 35. The compound of claim 34, which is alkyl.

43. Each R ６ are independently halogen, -(CH ２ ) ０－４ CO ２ H, -(CH ２ ) ０－４ CO(N-proline), -(CH ２ ) ０－４ C(O)NR ａ (CH ２ ) １－４ CO ２ H, -OH, -(CH ２ ) １－４ OH, -(CH ２ ) ０－４ SO ３ H. - (CH ２ ) ０－４ SO ２ NH ２ , -(CH ２ ) ０－４ NR ａ SO ２ C １－４ Alkyl, -(CH ２ ) ０－４ OP (OH) ２ , or -(CR ２ ) ０－４ OP(O)(H)OH, and R ａ is, independently for each occurrence, H, or C １－４ 35. The compound of claim 34, which is alkyl.

44. Each R ６ are independently a halogen, —CO ２ H. -CO(N-proline), -C(O)NR ａ (CH ２ ) １－４ CO ２ H, —OH, —SO ３ H, -SO ２ NH ２ , -NR ａ SO ２ C １－４ Alkyl, -OP(OH) ２ or —OP(O)(H)OH, and R ａ is, independently for each occurrence, H, or C １－４ 35. The compound of claim 34, which is alkyl.

45. R ６ is R Ｂ The compound of claim 1 which is not

46. At least one R ６ is terminal -CO ２ H or -CO ２ C １－４ The compound of claim 1 comprising an alkyl group.

47. At least one R ６ But -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ H, -(CH ２ ) ０－４ O (CH ２ ) １－５ CO ２ C １－４ Alkyl, -(CH ２ ) ０－４ CO ２ H, or -(CH ２ ) ０－４ CO ２ C １－４ 47. The compound of claim 46, which is alkyl.

48. At least one R ６ but [Chemistry 18] 47. The compound of claim 46, wherein:

49. A compound selected from: Table 1-1 Table 1-2 Table 1-3 Table 1-4 Table 1-5 Table 2-1 Table 2-2 Table 2-3 or a pharmaceutically acceptable salt thereof.

50. The compound of claim 1, wherein: [Transformation 50] or a pharmaceutically acceptable salt thereof.

51. A pharmaceutical composition comprising a compound according to any one of claims 1 to 50.

52. 51. A pharmaceutical composition comprising a compound of any one of claims 1 to 50 for use in antagonizing cyclic GMP-AMP synthase (cGAS) in a patient in need thereof.

53. 51. A pharmaceutical composition comprising a compound of any one of claims 1 to 50 for use in treating an inflammatory disease, an allergic disease, an autoimmune disease, an ocular inflammation, a cardiovascular disease or a neurodegenerative disease in a patient in need thereof.

Images