Nucleic acid binder

Abstract

The present invention relates to compounds suitable as RNA or DNA binders. RNA or DNA binders are useful for the treatment of various conditions, including those caused by microbial infections and cancer. The present invention relates to specific compounds and such compounds for use in treatment methods, such as the treatment of antibacterial infections and / or cancer.

Description

Technical Field

[0001] The present invention relates to compounds suitable as RNA or DNA binders. RNA or DNA binders are useful for the treatment of various conditions, including those caused by microbial infections and cancer. The present invention relates to certain compounds and such compounds for use in treatment methods, such as the treatment of antimicrobial infections and / or cancer.

Background Art

[0002] Many available antibacterial agents have been rendered ineffective and will be rendered ineffective due to the acquisition of resistance by pathogenic organisms. For certain applications, such as emergency prophylaxis, a broad-spectrum anti-infective agent is desirable, either in a clinic or on a battlefield. These may have a broad spectrum within a particular type of pathogen, for example within broad-spectrum antifungals, or may have a broad spectrum across different pathogen types, for example compounds that are antibacterial, antifungal, antiparasitic, and antiviral agents. In certain applications, where the specific pathogen causing the infection is known, this can prevent side effects, such as when the gastrointestinal microbiota is disrupted during treatment with antibiotics, or can reduce the rate of development of antibacterial resistance, and thus a narrow-spectrum agent is desirable.

[0003] DNA is an important target for drug action such as antibacterial drug action. DNA binders are typically classified by their binding modes (either intercalators or groove binders). DNA intercalators are typically planar aromatic compounds that can fit between the base pairs of DNA, while groove binders are typically aromatic compounds that can bind to either or both of the two channels (typically of the B-type) on the outer surface of double-stranded DNA, i.e., the major groove and the minor groove. The major groove contains approximately twice the number of potential hydrogen bond contacts as the minor groove. Considering this point, the major groove is the preferred recognition site for cellular proteins such as regulatory proteins, promoters, and repressors. In contrast, the minor groove is relatively unoccupied. The vulnerability of the minor groove makes it a particularly useful target for compounds that bind to DNA, which is the binding site for some naturally occurring antibiotics (such as netropsin and distamycin).

[0004] RNA is the genetic material of many pathogenic viruses and is also an important target for drug action. RNA exists in either single-stranded or double-stranded form, generally being single-stranded. RNA has a variable structure but most often exists in a helical structure known as the A-type. Double-stranded RNA also typically adopts the A-type helical structure. The minor groove and the major groove of the A-type RNA double-strand are very different from those of B-type DNA. That is, the minor groove and the major groove have different shapes (the major groove is narrower and deeper, and the minor groove is wider and shallower for A-type RNA compared to B-type DNA), and in the chemical environment, the 2'-OH of RNA is located in the minor groove.

[0005] Compounds having an affinity for DNA (especially MGB) are described in WO 2008 / 038018 (University of Strathclyde). These compounds are described as having an anti-infective effect by binding to the minor groove of DNA and interfering with DNA-centered processes within pathogens. More recently, compounds having related structures that can also bind to RNA have been identified, and these are known as nucleic acid binders (NAB) to explain this additional mechanism of action. SUMMARY OF THE INVENTION

Problems to be Solved by the Invention

[0006] Despite having strong activity, many NABs are unsuitable as drugs due to an unfavorable selectivity index between the pathogen and the host. In the art, alternative NABs with preferably improved selectivity are needed, and the present invention addresses this need.

Means for Solving the Problems

[0007] The present invention is based on the unexpected discovery that modification of the NAB structure via an increase or decrease in the chain length within the structure results in the production of NABs with selective toxicity in combination with effective DNA and RNA binding and potent anti-infective activity. Accordingly, the present invention provides alternative NABs with improved selectivity that are useful for the treatment of antibacterial infections and / or cancer.

[0008] Viewed from a first aspect, the present invention provides a compound of any one of Formulas I, II, III, and IV:

Chemical Formula

Chemical formula

Chemical formula

Chemical formula

[0009] The inventors have found that modification of the lengths of the groups R, A, D, E, R 1 , G and J results in the production of compounds with unexpectedly improved selectivity, as measured by an increase in the selectivity index. The selectivity index is calculated by the inventors as the minimum inhibitory concentration (MIC) required to inhibit 50% of mammalian cell growth divided by the minimum inhibitory concentration (MIC) required to inhibit a specific percentage (50%, 80% or 99%) of microbial cell growth. In other words, a larger selectivity index corresponds to greater inhibition of pathogen cells than host cells, and thus more selective compounds are advantageous as drugs.

[0010] Viewed from a second aspect, the present invention provides a composition comprising one or more compounds of the first aspect and a pharmaceutically acceptable excipient.

[0011] As described above, the compounds of the present invention exhibit improved selectivity and are useful for the treatment of antibacterial infections and / or cancer. Thus, viewed from a third aspect, the present invention provides a compound of the first aspect or a composition of the second aspect for use as a medicament.

[0012] Viewed from a fourth aspect, the present invention provides a compound of the first aspect or a composition of the second aspect for use in the treatment of any one or more selected from the group consisting of viral infections, bacterial infections, fungal infections, parasitic infections and cancer.

[0013] Viewed from a fifth aspect, the present invention provides a method for treating any one or more selected from the group consisting of viral infections, bacterial infections, fungal infections, parasitic infections and cancer, the method comprising administering an effective amount of a compound of the first aspect or a composition of the second aspect to a patient in need thereof.

[0014] As described above, the inventors have found that the compounds of the present invention can bind to DNA and RNA and are thus known as nucleic acid binders (NABs). Thus, in a sixth aspect, the present invention provides the use of a compound of the first aspect or a composition of the second aspect in the binding of RNA or DNA, wherein the binding is ex vivo or in vitro.

Mode for Carrying Out the Invention

[0015] (Detailed Description of the Invention) As described above, the inventors have found that modification of the NAB structure by increasing or decreasing the chain length within the structure results in the production of compounds with improved selectivity that are useful in the treatment of infectious diseases and / or cancer.

[0016] In the following discussion, many terms are referred to that are to be understood as having the meanings provided below, unless the context indicates otherwise. The nomenclature used herein to define compounds, particularly the compounds described herein, is intended to follow the rules of the International Union of Pure and Applied Chemistry (IUPAC) for chemical compounds, particularly the "IUPAC Compendium of Chemical Terminology (Gold Book)" (AD Jenkins et al, Pure & Appl Chem., 68, 2287-2311 (1996)). To avoid misunderstanding, where the IUPAC rules conflict with the definitions provided herein, the definitions herein shall prevail.

[0017] The term "comprising" or variations thereof is understood to mean the inclusion of the recited element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

[0018] The term "consisting" or variations thereof is understood to mean the exclusion of intervening elements, integers or steps, or groups of elements, integers or steps, described, and any other elements, integers or steps, or groups of elements, integers or steps.

[0019] As used herein, the term "about" when modifying a number or value is used to refer to a value within ±5% of the specified value. For example, if it is shown that a suitable daily dose is from about 0.1 to about 100 mg / kg, doses of 0.095 to 105 mg / kg are included.

[0020] The term "alkyl" is well known in the art and defines a monovalent group derived from an alkane by removing a hydrogen atom from any carbon atom, and the term "alkane" is of the general formula C n H 2n+2 (wherein n is ≧1) and is intended to define an acyclic branched or unbranched hydrocarbon. Examples of alkyl groups include methyl, ethyl, n-propyl, iso-propyl, n-butyl, sec-butyl, iso-butyl and tert-butyl.

[0021] The term "haloalkyl" refers to an alkyl group in which at least one hydrogen atom is replaced by a halo atom, such as fluoro, chloro or bromo, often fluoro. Trifluoromethyl is an example of a haloalkyl.

[0022] The term "alkylene" is used synonymously with the term "alkanediyl" and defines a divalent group derived from an alkane by removing two hydrogen atoms from any carbon atom (including the removal of two hydrogen atoms from the same carbon atom). C 2 -C 4 Alkylene refers to any one selected from the group consisting of ethylene, n-propylene, iso-propylene, n-butylene, sec-butylene, iso-butylene and tert-butylene.

[0023] The term "haloalkylene" refers to an alkylene group in which at least one hydrogen atom is replaced by a halo atom, such as fluoro, chloro or bromo, often fluoro. Tetrafluoroethylene is an example of a haloalkylene.

[0024] The term "cycloalkane" defines a saturated monocyclic unbranched hydrocarbon having the general formula C n H 2n (wherein n is an integer of 3 or more). C 3 - 6 Cycloalkyl refers to any one selected from the group consisting of cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl.

[0025] The term "cycloalkyl" defines all monovalent groups derived from cycloalkanes by removing one hydrogen atom from a ring carbon atom.

[0026] The term "alkenyl" defines a monovalent group derived from an alkene by removing a hydrogen atom from any carbon atom, and the term "alkene" is intended to define an acyclic branched or unbranched hydrocarbon having the general formula C n H 2n (wherein n is ≧ 2). Examples of alkenyl groups include ethenyl, n-propenyl, iso-propenyl, n-butenyl, sec-butenyl, iso-butenyl and tert-butenyl.

[0027] The term "dienyl" means a monovalent group derived from a diene by removing a hydrogen atom from any carbon atom, and the term "diene" defines an acyclic branched or unbranched hydrocarbon having the general formula C n H 2n-2 Similarly, the term "trikenyl" means a monovalent group derived from a triene by removing a hydrogen atom from any carbon atom, and the term "triene" defines an acyclic branched or unbranched hydrocarbon having the general formula C n H 2n-4 ​

[0028] The term "alkoxy" defines a monovalent group derived from an alcohol by removal of the hydrogen atom bonded to the hydroxyl group. The term "alcohol" defines a group derived from an alkane in which one hydrogen atom is replaced by a hydroxyl group. Methoxy is an example of an alkoxy group of C 1 of.

[0029] The term "aryl" defines all monovalent groups formed by removing a hydrogen atom from an arene ring carbon, and the term "arylene" defines all divalent groups formed by removing two hydrogen atoms from an arene ring carbon. The term "arene" defines a monocyclic or polycyclic aromatic hydrocarbon, where "aromatic" defines a cyclic conjugated molecular entity having a stability (due to delocalization) significantly greater than that of a hypothetical localized structure. The Hückel rule is often used in the art to evaluate aromaticity, and a monocyclic planar (or nearly planar) system of triangular (or sometimes digonal) hybrid atoms containing (4n + 2)π electrons (n is a non-negative integer) exhibits aromaticity. Usually, this rule is restricted to n = 0 to 5.

[0030] The term "naphthylene" refers to a monovalent group derived from naphthalene by removing a hydrogen atom from a carbon atom.

[0031] The term "heteroarene" defines a compound formally derived from an arene by replacing one or more methine (-C=) and / or vinylene (-CH=CH-) groups with trivalent or divalent heteroatoms, respectively, in such a way as to maintain a continuous π-electron system characteristic of the aromatic system. The term "heteroaryl" defines all monovalent groups formed by removing a hydrogen atom from a heteroarene ring atom such as carbon or nitrogen, and the term "heteroarylene" defines all divalent groups formed by removing two hydrogen atoms from a heteroarene ring atom such as carbon or nitrogen. Typically, the heteroaryl or heteroarylene groups herein contain any one or combination of heteroatoms selected from the group consisting of nitrogen, oxygen, and sulfur atoms.

[0032] The term "heterocyclyl" defines all monovalent groups formed by removing a hydrogen atom from a heterocyclic ring atom such as carbon or nitrogen. The term "heterocycle" defines a cyclic compound having ring member atoms of at least two different elements, typically carbon and one or more heteroatoms such as nitrogen, oxygen, and / or sulfur. This term encompasses aromatic (heteroarene) and non-aromatic compounds.

[0033] To avoid ambiguity, methoxy (ethoxy) 1-3 means -(OOOA) 1-3 -OOOC, and hydroxy (ethoxy) 1-3 means -(OOOA)-OH. Also, di(C 1-4 alkyl)amino means N(C 1-4 alkyl) 2 and C 1-4 alkylamino means NH(C 1-4 alkyl), and amino means NH 2 . - The term "treatment" defines a therapeutic treatment of a subject who can be a human or a non-human animal (e.g., a domestic animal such as a farm animal) for the purpose of interfering with, reducing, or halting the rate of progression of a condition, or for improving or curing a condition. Prevention of symptoms as a result of treatment is also included. Reference to prevention is intended herein not to require complete prevention of a condition, the development of which can instead be impeded by treatment according to the invention. In certain instances, the term "is used to define a therapeutic treatment of a subject for the purpose of interfering with, reducing, or halting the rate of progression of a sclerosing condition, or for improving or treating a condition. In these instances, the subject has the condition.

[0034] As used herein, "effective amount" defines an amount of any one or combination of the compounds or compositions described herein sufficient to interfere with a condition and thus bring about the desired therapeutic or inhibitory effect.

[0035] The term "ex vivo" is used herein to refer to a process that is carried out within or on a tissue taken from an organism in an external environment.

[0036] The term "in vitro" is used herein to refer to a process that is carried out outside of their normal biological context using microorganisms, cells, or biological molecules.

[0037] The term "stereoisomer" is used herein to refer to isomers that have the same molecular formula and sequence of bonded atoms, but differ in the arrangement of those atoms in space.

[0038] The term "enantiomer" defines one of a pair of molecular entities that are mirror images of each other and cannot be superimposed, i.e., cannot be made to coincide by translation and rigid body rotation. Enantiomers are chiral molecules, i.e., they are distinguishable from their mirror images.

[0039] The term "racemate" is used herein with respect to racemates. As used herein, a racemate defines a substantially equimolar mixture of a pair of enantiomers (about 50% of one enantiomer and about 50% of the other enantiomer). The term "diastereoisomer" (also known as diastereomer) defines stereoisomers that are not related as mirror images.

[0040] The term "solvate" is used herein to refer to a complex comprising a solute, such as a compound or a salt of a compound, and a solvent. When the solvent is water, the solvate may be referred to as a hydrate, such as a monohydrate, dihydrate, trihydrate, etc., depending on the number of water molecules present per molecule of the substrate.

[0041] The term "isotope" is used herein to define variants of a particular chemical element that necessarily have the same atomic number but different mass numbers because they have different numbers of neutrons.

[0042] The term "prodrug" is used herein to refer to a compound that acts as a drug precursor and, when administered to a subject, is converted by metabolism or another chemical process to yield a compound disclosed herein.

[0043] The term "pharmaceutically acceptable excipient" defines substances other than pharmaceutically active drugs or prodrugs, which are included in pharmaceutical products.

[0044] The term "enteral" is used to refer to the administration of a compound through the gastrointestinal tract. Enteral administration can be oral administration, i.e., administration via the mouth.

[0045] The term "parenteral" is used to refer to the administration of a compound into the body by means other than through the gastrointestinal tract. Parenteral administration includes intravenous administration (directly into a vein), intramuscular administration (into a muscle), intradermal administration (into the skin) or subcutaneous administration (under the skin, e.g., into fat). Parenteral administration can be effected via a bolus injection in which a discrete amount of the compound is administered in a single injection.

[0046] Unless otherwise specified, the term "RNA" refers to either single-stranded or double-stranded RNA, and the term "RNA sequence" includes any portion (or the whole) of an RNA oligomer or polymer spanning three or more bases. "DNA" refers to either single-stranded or double-stranded DNA, and the term "DNA sequence" includes any portion (or the whole) of a DNA oligomer or polymer spanning three or more base pairs.

[0047] The term "virus containing RNA" is used interchangeably herein with the term "RNA virus" and refers to a virus that contains RNA as its genetic material. RNA viruses belong to Group III, Group IV, Group V, or Group VI of the Baltimore classification, i.e., those containing double-stranded RNA, plus-sense single-stranded RNA (including those having a DNA intermediate in their life cycle such as retroviruses), or antisense (or negative-sense) single-stranded RNA.

[0048] As described above, in a first aspect, the present invention provides a compound of any one of Formulas I, II, III, and IV:

Chemical formula

Chemical formula

Chemical Formula

Chemical Formula

[0049] As described above, Q a (Of formulas I, II, III and IV) is optionally substituted aryl or optionally substituted heteroaryl, and Q b (Of formulas I, II, III and IV) is optionally substituted arylene or optionally substituted heteroarylene. To avoid misunderstanding, Q b Is a biradical bonded to -CH= and -C(O)-.

[0050] Q a The aryl and heteroaryl of Q and Q b The arylene and heteroarylene of Q are N(C 1-6 Alkyl) 2 Halo C 1-6 Alkyl, cyano, C 1-6 Alkyl, C 1-6 Alkoxy group, NH(C 1-6 Alkyl), NH 2 Optionally substituted with any one or a combination selected from the group consisting of, halo and OH. In many cases, halo C 1-6 Alkyl is fluoro C 1-6 Alkyl, and halo is fluoro. In some cases, the C of each relevant substituent 1-6 Alkyl is C such as methyl 1-4 Alkyl, that is, N(C 1-6 Alkyl) 2 Is dimethylamino, and halo C 1-6The alkyl is halomethyl, C 1-6 The alkyl is methyl, the alkoxy is methoxy, and NH(C 1-6 alkyl) is methylamino.

[0051] In some embodiments, Q a and Q b are N(C 1-6 alkyl) 2 (for example, N(C 1-4 alkyl) 2 , for example, dimethylamino), haloC 1-6 alkyl (for example, haloC 1-4 alkyl, for example, trifluoromethyl or trifluoroethyl), cyano, C 1-6 alkyl (for example, C 1-4 alkyl, for example, methyl or ethyl) and C 1-6 alkoxy (for example, C 1-4 alkoxy, for example, methoxy), optionally substituted with any one or combination selected from the group consisting of.

[0052] In some embodiments, Q a and Q b are N(C 1-4 alkyl) 2 (for example, dimethylamino), haloC 1-4 alkyl (for example, trifluoromethyl or trifluoroethyl), cyano, C 1-4 alkyl (for example, methyl or ethyl), C 1-4 alkoxy group (for example, methoxy) and halo (for example, fluoro), optionally substituted with any one or combination selected from the group consisting of.

[0053] In some embodiments, Q a and Q b are N(C 1-4 alkyl) 2 (for example, dimethylamino), haloC 1-4 alkyl (for example, trifluoromethyl or trifluoroethyl), cyano, C 1-4Alkyl (e.g., methyl or ethyl) and C 1-4 Optionally substituted with any one or combination selected from the group consisting of an alkoxy group (e.g., methoxy).

[0054] In some embodiments, Q a and Q b May be substituted with any one or combination selected from the group consisting of N(CH 3 ), halomethyl, cyano, methyl, methoxy group, and fluoro. 2

[0055] In some embodiments, Q a and Q b Are optionally substituted with any one or combination selected from the group consisting of N(CH 3 ), halomethyl, cyano, methyl, and methoxy group. 2

[0056] Often, when Q a is heteroaryl, it is unsubstituted.

[0057] In some embodiments, Q a Is selected from the group consisting of phenyl, quinolinyl (such as quinolin-3-yl), benzoxadiazolyl (such as benzoxydiazole-5-yl), naphthalenyl (such as naphthalene-2-yl), benzothiazolyl group (such as benzothiazole-2-yl), isoquinolinyl, thiazolyl group, pyridinyl, pyrimidinyl, thiophenyl, pyridazinyl, phthalazinyl, imidazolyl, and pyrrolyl, which may be substituted. Often, quinolinyl (e.g., quinolin-3-yl), benzoxadiazolyl (e.g., benzoxydiazole-5-yl), benzothiazolyl group (e.g., benzothiazole-2-yl), isoquinolinyl, thiazolyl group, pyridinyl, pyrimidinyl, thiophenyl, pyridazinyl, phthalazinyl, imidazolyl, and pyrrolyl are unsubstituted.

[0058] In some embodiments, Q a ​​Phenyl, quinolinyl (such as quinolin-3-yl), benzoxadiazolyl (such as benzoxazol-5-yl), naphthalenyl (such as naphthalene-2-yl) and benzothiazolyl (such as benzothiazol-2-yl) which may be substituted, for example phenyl which may be substituted, quinolinyl which may not be substituted, substituted. In some cases, Q a Is selected from the group consisting of phenyl which may be substituted, unsubstituted quinolin-3-yl, unsubstituted benzoxazol-5-yl, naphthalen-2-yl which may be substituted and unsubstituted benzothiazol-2-yl.

[0059] In some embodiments, Q b Is monocyclic. In some cases, Q b Is selected from the group consisting of phenylene which may be substituted (for example, benzene-1,4-diyl), pyridinyl (for example, pyridine-2,5-diyl), thiazolyl, pyrimidinediyl, thiophenediyl, pyridazinediyl, imidazolidyl and pyrrolidyl (for example, phenylene which may be substituted and pyridinediyl). In many cases, Q b Is benzene-1,4-diyl which may be substituted or pyridine-2,5-diyl.

[0060] In some embodiments, for example, in the case of monocyclic, Q b Is unsubstituted such as unsubstituted benzene-1,4-diyl or pyridine-2,5-diyl.

[0061] As described above, each R (of Formulas I, II and IV) is C 1-6 Alkyl, H and halo C 1-6 Alkyl, for example C 1-4 Alkyl, H and halo C 1-4 Alkyl (for example fluoro C 1-4 Alkyl) is independently selected from the group consisting of. In many cases, each R is independently selected from the group consisting of methyl, H and fluoromethyl (such as trifluoromethyl).

[0062] In some embodiments, each R is independently selected from the group consisting of C such as methyl and H 1-4 and the like. In many cases, each R is methyl.

[0063] As described above, A (in Formulas I and III) is C 1-6 alkylene or halo C 1-6 alkylene (such as fluoro C 1-6 alkylene). In some embodiments, A is C 1-6 alkylene, for example C 2-5 alkylene. Typically, A is unbranched such as any one selected from the group consisting of n-ethylene, n-propylene, n-butylene, and n-pentylene.

[0064] Z (in Formulas Id and IVb) is selected from the group consisting of O, CH 2 , N(C 1-6 alkyl) (for example, N(C 1-4 alkyl)) and S. In some embodiments, Z is selected from the group consisting of O, CH 2 , N(CH 3 ) and S. In some embodiments, Z in Formula IVb is CH 2 or S. -

[0065] In some cases, the compound is of Formula I. In such cases, A-D are often selected from the group consisting of Formulas Ia, Ib, and Ic, for example Ia and Ib (for example Ia).

[0066] As described above, each R 2 (Ia) is independently selected from the group consisting of H, C 1-20 alkyl, C 1-20 alkoxy, C 2-20 alkenyl, C 4-20 dialkenyl, and C 6-20 trialkenyl, where at least one R 2 is not H, and is C 1-20 alkyl, C 1-20Alkoxy, C 2-20 Alkenyl, C 4-20 Dialkenyl and C 6-20 Trialkenyl are aryl, heterocyclyl, N(C 1-6 Alkyl) 2 , methoxy(ethoxy) 1-3 , hydroxy(ethoxy) 1-3 , cycloC 3-8 Alkyl, halo, cyano, C 1-6 Alkoxy, NH(C 1-6 Alkyl), NH 2 =O and OH, independently selected from the group consisting of any one or more, optionally substituted, where aryl and heterocyclyl are C 1-4 Alkyl, haloC 1-4 Alkyl, C 1-4 Alkoxy and halo, independently selected from the group consisting of any one or more, optionally substituted. Typically, optionally substituted C 1-20 Alkyl, C 1-20 Alkoxy group, C 2-20 Alkenyl, C 4-20 Dialkenyl and C 6-20 Trialkenyl are optionally substituted R 2 Of C 1-9 Alkyl, C 1-9 Alkoxy group, C 2-9 Alkenyl, dialkenyl and C 6-9 Trialkenyl.

[0067] Often, each R 2 Is H, optionally substituted C 1-9 Alkyl and optionally substituted C 1-9 Alkoxy, independently selected from the group consisting of, where at least one R 2 Is not H. Optionally substituted C 1-9 Alkoxy is a methoxy group, that is, each R 2 Is, H, optionally substituted C 1-9 Alkyl and methoxy group, independently selected from the group consisting of, where at least one R 2 Is not H.

[0068] As described above, R 2 any substituent of the alkyl, alkoxy, alkenyl, dialkenyl and trialkenyl groups is aryl, heterocyclyl, N(C 1-6 alkyl) 2 , methoxy(ethoxy) 1-3 , hydroxy(ethoxy) 1-3 , cycloC 3-8 alkyl, halo, cyano, C 1-6 alkoxy, NH(C 1-6 alkyl), NH 2 , =O and OH, and consists of any one or more independently selected from the group consisting of, wherein aryl and heterocyclyl are C 1-4 alkyl, haloC 1-4 alkyl, C 1-4 alkoxy and halo, and is optionally substituted with any one or more independently selected from the group consisting of.

[0069] Often, the optionally substituted aryl and heterocyclyl of R 2 are monocyclic. In some cases, the optionally substituted aryl of R 2 is optionally substituted phenyl (such as unsubstituted phenyl). In some cases, the optionally substituted heterocyclyl of R 2 is optionally substituted piperazinyl (for example, 1-(C 1-6 alkyl)piperazinyl), optionally substituted tetrahydropyranyl (for example, unsubstituted tetrahydropyranyl), or optionally substituted thiomorpholinyl (for example, unsubstituted thiomorpholinyl). In some cases, the optionally substituted heterocyclyl of R 2 is optionally substituted piperazinyl (for example, 1-(C 1-6 alkyl)piperazinyl) or optionally substituted tetrahydropyranyl (for example, unsubstituted tetrahydropyranyl).

[0070] Often, R 2Any substituent of the alkyl, alkoxy, alkenyl, dialkenyl and trialkenyl groups is phenyl, 1-(C 1-6 alkyl)piperazinyl, tetrahydropyranyl, N(C 1-6 alkyl) 2 (N(C 1-3 alkyl) 2 etc.), methoxy(ethoxy) 1-3 (methoxy(ethoxy) 1-2 etc.), hydroxy(ethoxy) 1-3 (hydroxy(ethoxy) 1-2 etc.), thiomorpholinyl, C 1-3 alkoxy(methoxy etc.) and halo(fluoro etc.) and is independently selected from any one or more of the group consisting of.

[0071] Often, any substituent of the alkyl, alkoxy, alkenyl, dialkenyl and trialkenyl groups of R 2 is phenyl, 1-(C 1-6 alkyl)piperazinyl, tetrahydropyranyl, N(C 1-6 alkyl) 2 (N(C 1-3 alkyl) 2 etc.), methoxy(ethoxy) 1-3 (methoxy(ethoxy) 1-2 etc.), and hydroxyl(ethoxy) 1-3 (hydroxyl(ethoxy) etc.) and is independently selected from any one or more of the group consisting of.

[0072] In some embodiments, each R 2 is independently selected from the group consisting of H, C 1-9 alkyl, C 1-9 alkoxy, C 2-9 alkenyl, C 4-9 dialkenyl and C 6-9 trialkenyl, and at least one R 2 is not H, but C 1-9 alkyl, C 1-9 alkoxy, C 2-9 alkenyl, C 4-9 dialkenyl and C 6-9Trialkenyl is optionally substituted with any one or more independently selected from the group consisting of phenyl, 1-(C 1-6 alkyl)piperazinyl, tetrahydropyranyl, N(C 1-6 alkyl) 2 ), methoxy(ethoxy) 1-3 ), and hydroxy(ethoxy) 1-3 ).

[0073] In some embodiments, each R 2 is independently selected from the group consisting of H, C 1-9 alkyl, and C 1-9 alkoxy groups, and at least one R 2 is not H, and the C 1-9 alkyl and C 1-9 alkoxy groups are optionally substituted with any one or more independently selected from the group consisting of phenyl group, 1-(methyl)piperazinyl, tetrahydropyranyl, N(C 1-3 alkyl) 2 ), methoxy group(ethoxy) 1-2 ), hydroxyl group(ethoxy), thiomorpholinyl, methoxy group, and fluoro.

[0074] In more specific embodiments, each R 2 is independently selected from the group consisting of H, C 1-9 alkyl, and C 1-9 alkoxy groups, and at least one R 2 is not H, and the C 1-9 alkyl and C 1-9 alkoxy groups are optionally substituted with any one or more independently selected from the group consisting of phenyl group, 1-(methyl)piperazinyl, tetrahydropyranyl, N(C 1-3 alkyl) 2 ), methoxy(ethoxy) 1-2 ), and hydroxyl group(ethoxy) 1-2 ).

[0075] Optionally, when one R 2 is ethyl, the other is not ethyl. When R 2 is a propyl group, Qa may not be methoxyphenyl. In some cases, R 2 is not a propyl group.

[0076] As described above, each R 3 (Ic) is C 1-20 alkyl, C 2-20 alkenyl, C 4-20 dialkenyl and C 6-20 trialkenyl, independently selected from the group consisting of, aryl, heterocyclyl, N(C 1-6 alkyl) 2 , methoxy(ethoxy) 1-3 , hydroxy(ethoxy) 1-3 , hydroxy(ethoxy) 1-3 , cycloCR 3 alkyl, halo, cyano, C 1-20 alkoxy, NH(C 2-20 alkyl), C 4-20 =O, and OH, and may be substituted with any one or more independently selected from the group consisting of, and aryl and heterocyclyl are C 6-20 alkyl, haloCC 1-6 alkyl, 2 alkoxy and halo, and may be substituted with any one or more independently selected from the group consisting of. Typically, each R 3 is optionally substituted C 1-20 alkyl.

[0077] In many cases, the optionally substituted aryl and heterocyclyl of R 3 are monocyclic. In some cases, the optionally substituted aryl of R 3 is optionally substituted phenyl (such as unsubstituted phenyl). In some cases, the optionally substituted heterocyclyl of R 3 is optionally substituted piperazinyl (for example, 1-(C 1-6 alkyl)piperazinyl, for example, 1-methylpiperazinyl) or optionally substituted tetrahydropyranyl (for example, unsubstituted tetrahydropyranyl).

[0078] In many cases, R 3 any substituent of the alkyl, alkenyl, dialkenyl and trialkenyl groups of is phenyl, 1-(C 1-6 alkyl)piperazinyl (such as 1-(methyl)piperazinyl), tetrahydropyranyl, N(C 1-6 alkyl) 2 (N(C 1-3 alkyl) 2 etc.), methoxy (ethoxy) 1-3 (methoxy (ethoxy) 1-2 etc.), and hydroxyl (ethoxy) 1-3 (hydroxyl (ethoxy) etc.) and is independently selected from any one or more of the group consisting of.

[0079] In some embodiments, each R 3 is independently C 1-20 alkyl, and is optionally substituted with any one or more independently selected from the group consisting of a phenyl group, 1-(methyl)piperazinyl, tetrahydropyranyl, N(C 1-3 alkyl) 2 , methoxy (ethoxy) 1-2 , and hydroxyl (ethoxy) 1-2. .

[0080] In some embodiments, each R 3 contains less than 18 carbon atoms, for example, 12 or fewer carbon atoms.

[0081] In certain embodiments, each R 3 is independently C 1-2 alkyl optionally substituted with any one or more independently selected from the group consisting of methoxy (ethoxy) 1-2 and hydroxyl (ethoxy) 1-20 .

[0082] As described above, R (of formula Id) 4 is C 2-20 alkyl, C 2-20 alkenyl, C 4-20 dialkenyl and C 6-20Selected from the group consisting of trialkenyl, aryl, heterocyclyl, N(C 1-6 alkyl) 2 、methoxy(ethoxy) 1-3 、hydroxy(ethoxy) 1-3 、hydroxy(ethoxy) 1-3 、cycloCR 4 alkyl, halo, cyano, C 2-20 alkoxy, NH(C 2-20 alkyl), C 4-20 、=O and OH, and is optionally substituted with any one or more independently selected from the group consisting of, aryl and heterocyclyl are C 6-20 alkyl, haloCC 1-6 alkyl, 2 alkoxy and halo, and is optionally substituted with any one or more independently selected from the group consisting of. Typically, R 4 is optionally substituted C 2-20 alkyl, for example optionally substituted C 2-10 alkyl.

[0083] In some embodiments, R 4 contains at least 5 or 6 carbon atoms, for example, R 4 is optionally substituted C 5-20 alkyl or C 6-20 alkyl, for example, optionally substituted C 5-10 alkyl or C 6-10 alkyl may be. Alternatively, if R 4 is C 1-2 alkyl or C 1-4 alkyl, then it is aryl, heterocyclyl, N(C 1-6 alkyl) 2 、methoxy(ethoxy) 1-3 、hydroxy(ethoxy) 1-3 、cycloC 3-8 alkyl, cyano, C 1-6 alkoxy, NH(C 1-6 alkyl), NH 2 =O and OH, and is optionally substituted with any one or more independently selected from the group consisting of, wherein aryl and heterocyclyl are C1-4 Alkyl, halo C 1-4 Alkyl, C 1-4 It may be optionally substituted with any one or more independently selected from the group consisting of alkoxy and halo.

[0084] Often, R 4 The optionally substituted aryl and heterocyclyl are monocyclic. In some cases, R 4 The optionally substituted aryl is optionally substituted phenyl (such as unsubstituted phenyl). In some cases, R 4 The optionally substituted heterocyclyl is optionally substituted piperazinyl (e.g., 1-(C 1-6 alkyl)piperazinyl, e.g., 1-methylpiperazinyl) or optionally substituted tetrahydropyranyl (e.g., unsubstituted tetrahydropyranyl).

[0085] Often, R 4 Any substituent of the alkyl, alkenyl, dialkenyl, and trialkenyl groups is phenyl, 1-(C 1-6 alkyl)piperazinyl (such as 1-(methyl)piperazinyl), tetrahydropyranyl, N(C 1-6 alkyl) 2 (N(C 1-3 alkyl) 2 etc.), methoxy (ethoxy) 1-3 (methoxy (ethoxy) 1-2 etc.), and hydroxyl (ethoxy) 1-3 (hydroxyl (ethoxy) etc.) and consists of any one or more independently selected from the group.

[0086] In some embodiments, R 4 is independently C 2-20 alkyl and is optionally substituted with any one or more independently selected from the group consisting of phenyl group, 1-(methyl)piperazinyl, tetrahydropyranyl, N(C 1-3 alkyl) 2 , methoxy (ethoxy) 1-2 , and hydroxyl (ethoxy) 1-2. .

[0087] In certain embodiments, R 4 is unsubstituted C 2-10 alkyl. In many cases, R 4 is unsubstituted and unbranched C 2-10 alkyl.

[0088] As noted above, A - D are selected from the group consisting of Formulas Ia - Id, i.e., in some embodiments A - D is Ia, in some embodiments A - D is Ib, in some embodiments A - D is Ic, and in some embodiments A - D is Id. To avoid misunderstanding, when A - D is Ic or Id, the nitrogen atom bonded to A and R 3 or R 4 is positively charged. The positive charge may be stabilized by a counterion (typically it is), i.e., the compound is typically a cation stabilized by an anion to form a salt. An overview of pharmaceutical salts is provided by P H Stahl and C G Wermuth in Pharmaceutical Salts: Properties, Selection and Use, Weinheim / Zurich: Wiley - VCH / VHCA, 2 nd Revised Edition, 2011. When the compound is a cation, it can be stabilized by one or more of the anions described in this review. The compound can be isolated from the reaction mixture as a pharmaceutically acceptable salt. Alternatively, a pharmaceutically acceptable salt can be prepared in - situ during isolation and purification of the compound or by treating the compound with a suitable acid, e.g., trifluoroacetic acid, benzenesulfonic acid, hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, acetic acid, propionic acid, glycolic acid, maleic acid, malonic acid, methanesulfonic acid, fumaric acid, succinic acid, tartaric acid, citric acid, benzoic acid, and ascorbic acid. When the compound is a cation, it can be stabilized by one or more of the conjugate bases of the acids listed above.

[0089] In some embodiments, A-D are selected from the group consisting of formulas Ia and Ib, for example Ia.

[0090] Optionally, the compound is of formula II.

[0091] E in formula I is C 4-6 alkylene or halo C 4-6 alkylene (fluoro C 1-6 alkylene, etc.). In some embodiments, E is C 4-6 alkylene. Typically, E is unbranched such as any one selected from the group consisting of n-butylene, n-pentylene, and n-hexylene. Optionally, E is C 4 or C 5 alkylene, for example n-butylene or n-pentylene.

[0092] Optionally, the compound is of formula III.

[0093] As described above, each R 1 (III) is C 1-6 alkyl, H, and halo C 1-6 alkyl, for example, C 1-4 alkyl, H, and halo C 1-4 alkyl (for example, fluoro C 1-4 alkyl) independently selected from the group consisting of, wherein at least one R 1 is H. Sometimes, one R 1 is H and the other is selected from the group consisting of methyl, H, and fluoromethyl (for example, trifluoromethyl). In some aspects, one R 1 is H and the other is selected from the group consisting of C 1-4 alkyl and H, for example methyl and H.

[0094] A-G (of formula III) is selected from the group consisting of formulae IIIa and IIIb, i.e., sometimes A-G is of formula IIIa and sometimes A-G is of formula IIIb. In some embodiments, A-G is of formula IIIa. When A-G is of formula IIIb, Q a may not be dimethylaminophenyl.

[0095] In some cases, the compound is of formula IV. In such cases, C(O)-J is often of formula IVa.

[0096] As described above, each R 5 (of formula IVa) is independently selected from the group consisting of H, C 1-20 alkyl, C 2-20 alkenyl, C 4-20 dialkenyl and C 6-20 trialkenyl, and C 2-20 alkenyl, C 4-20 dialkenyl and C 6-20 trialkenyl may be substituted with any one or more independently selected from the group consisting of methoxy(ethoxy) 1-3 , hydroxy(ethoxy)alkylamino, C 1-4 alkylamino, cyclo C 3-8 alkyl, pyrrolidinyl, piperazinyl, morpholinyl, thiomorpholinyl, aryl, halo, C 1-6 alkoxy, =O and OH, and C 1-20 alkyl may be methoxy(ethoxy) 1-3 , hydroxy(ethoxy) 1-3 , di(C 1-4 )alkylamino, amino, cyclo CC 1-4 alkyl, pyrrolidinyl, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, aryl, halo, cyano, C 1-6 (wherein cyclo C 3-8Alkyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, 1-(3-propyl)piperidine, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, and aryl are C 1-4 Alkyl, halo C 1-4 Alkyl, C 1-4 Alkoxy and halo, and may be optionally substituted with any one or more independently selected from the group consisting of). Typically, R 5 Optionally substituted C 1-20 Alkyl, C 2-20 Alkenyl, C 4-20 Dialkenyl and C 6-20 Trialkenyl may be optionally substituted C 1-12 Alkyl, C 2-12 Alkenyl, C 4-12 Dialkenyl and C 6-12 Trialkenyl.

[0097] In some embodiments, when the alkyl of R 5 is substituted with di(C 1-4 alkyl)amino, C 1-4 alkylamino, and amino substituents, the alkylene moiety contains at least 4 carbon atoms. For example, substituted C 4-20 alkyl or substituted C 7-20 alkyl. In some embodiments, the alkyl of R 5 is not substituted with di(C 1-4 )alkylamino, C 1-4 alkylamino, and amino substituents, i.e., methoxy(ethoxy) 1-3 , hydroxy(ethoxy) 1-3 , cyclo C 3-8 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, aryl, halo, cyano, C 1-6 alkoxy, =O, and OH, and may be optionally substituted with any one or more independently selected from the group consisting of. C 3-8Alkyl, pyrrolidinyl, piperidinyl, morpholinyl, thiomorpholinyl, 1-(3-propyl)piperidine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine and aryl are C 1-3 Alkyl, haloCC 1-6 Alkyl, C 1-4 Optionally substituted with any one or more independently selected from the group consisting of alkoxy and halo.

[0098] In some embodiments, when the alkyl of one R 5 is substituted with di(C 1-4 alkyl)amino, C 1-4 alkylamino and amino substituents, the other R 5 is not H.

[0099] Often, each R 5 is independently selected from the group consisting of H, optionally substituted C 1-12 and optionally substituted C 4-12 diallyl. In some cases, C 4-12 diallyl is unsubstituted, i.e., each R 5 is independently selected from the group consisting of H, optionally substituted C 1-12 and unsubstituted C 4-12 diallyl.

[0100] As described above, any substituent of the alkenyl group, diallyl group and triallyl group of R 5 is methoxy(ethoxy) 1-3 hydroxy(ethoxy) 1-3 di(C 1-4 alkyl)amino, C 1-4 alkylamino, cyclo C 3-8 alkyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, morpholinyl, thiomorpholinyl, aryl, halo, alkoxy, C 1-6 alkoxy, =O and OH, where cyclo C 3-8Alkyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, and aryl are C 1-4 alkyl, halo C 1-4 alkyl, C 1-4 Any one or more optionally substituted and independently selected from the group consisting of alkoxy and halo, consisting of any one or more.

[0101] In some cases, R 5 Any substituent of the alkenyl, dialkenyl, and trialkenyl groups is methoxy (ethoxy) 1-3 , hydroxyl (ethoxy) 1-3 , di(C 1-4 alkyl)amino, C 1-4 alkylamino , amino, and cyclo C 3-8 alkyl, consisting of any one or more independently selected from the group consisting of.

[0102] Often, R 5 The alkenyl group, dialkenyl group, and trialkenyl group are unsubstituted.

[0103] As described above, R 5 Any substituent of the alkyl group is methoxy (ethoxy) 1-3 , di(C 1-4 )alkylamino, C 1-4 , cyclo C 3-8 alkyl, pyrrolidinyl, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, aryl, cyano, C 1-6 alkoxy, =O, and OH, consisting of any one or more independently selected from the group consisting of, where cyclo C 3-8 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, and aryl are optionally, alkyl, halo C 1-4 alkyl, C 1-4 alkoxy, and halo, substituted with any one or more independently selected from the group consisting of.

[0104] In some embodiments, R 5 's alkyl group is not substituted with di(C 1-4 alkyl)amino, C 1-4 alkylamino and amino substituents, that is, the alkyl group of R 5 is methoxy(ethoxy) 1-3 , hydroxy(ethoxy) 1-3 , cyclo C 3-8 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, 4-(3-propyl)thiomorpholine, aryl, halo, cyano, C 1-6 alkoxy, =O and OH, and is composed of any one or more independently selected from the group consisting of cyclo C 3-8 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine and aryl are C 1-4 alkyl, halo C 1-4 alkyl, C 1-4 alkoxy and halo. Optionally, the optionally substituted aryl of R 5 is optionally substituted phenyl (such as unsubstituted phenyl). Optionally, the optionally substituted cyclo C 3-8 alkyl, pyrrolidinyl, 1-(3-propyl group)piperidine, 1-(3-propyl group)piperazine, 4-(3-propyl group)morpholine, 4-(3-propyl group)thiomorpholine and aryl are unsubstituted.

[0105] Often, any substituent of the alkyl group of R 5 is methoxy(ethoxy) 1-3 , hydroxyl group(ethoxy) 1-3 , di(C 1-4 alkyl)amino (such as dimethylamino), C 1-4 alkylamino (such as methylamino), amino, cyclo C 3-8Alkyl (such as cyclohexanyl or cyclopentanyl), pyrrolidinyl (such as N-pyrrolidinyl), 1-(3-propyl)piperidine, and C 1-6 It consists of any one or more independently selected from the group consisting of alkoxy (such as methoxy).

[0106] In many cases, R 5 Any substituent of the alkyl group is methoxy (ethoxy) 1-3 , hydroxyl group (ethoxy) 1-3 , di(C 1-4 alkyl)amino (such as dimethylamino), C 1-4 alkylamino (such as methylamino), amino, cyclo C 3-8 alkyl (such as cyclohexanyl or cyclopentanyl), pyrrolidinyl (such as N-pyrrolidinyl) and 1-(3-propyl)piperidine, and consists of any one or more independently selected from the group consisting of.

[0107] In some cases, R 5 Any substituent of the alkyl group is methoxy (ethoxy) 1-2 , hydroxyl group (ethoxy) 1-2 , dimethylamino, methylamino, amino, cyclo C 5-7 alkyl (for example, cyclohexanyl or cyclopentanyl), pyrrolidinyl (for example, N-pyrrolidinyl) and 1-(3-propyl)piperidine, and consists of any one or more independently selected from the group consisting of, and C 1-3 alkoxy (for example, methoxy).

[0108] In some cases, R 5 Any substituent of the alkyl group is methoxy (ethoxy) 1-2 , hydroxyl group (ethoxy) 1-2 , dimethylamino, methylamino, amino, cyclo C 5-7 alkyl (such as cyclohexanyl or cyclopentanyl), pyrrolidinyl (such as N-pyrrolidinyl) and 1-(3-propyl)piperidine, and consists of any one or more independently selected from the group consisting of.

[0109] In some embodiments, each R 5 is independently selected from the group consisting of H, C 1-12 alkyl, C 2-12 alkenyl, C 4-12 dienyl and C 6-12 trialkenyl, and C 2-12 alkenyl, C 4-12 dienyl and C 6-12 trialkenyl are methoxy(ethoxy) 1-3 , hydroxy(ethoxy)alkyl)amino, C 1-4 alkylamino, cycloCOO methoxy(ethoxy) 1-3 , hydroxy(ethoxy) 1-3 , di(C 1-4 alkyl)amino, amino, cycloC 1-3 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, 1-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, aryl and C 1-4 alkoxy.

[0110] In some embodiments, each R 5 is independently selected from the group consisting of H, C 1-12 alkyl, C 2-12 alkenyl, C 4-12 dienyl and C 6-12 trialkenyl, and C 2-12 alkenyl, C 4-12 dienyl and C 6-12 trialkenyl are methoxy(ethoxy) 1-3 , hydroxy(ethoxy)alkyl)amino, C 1-4 alkylamino, cycloC 3-8 alkyl, pyrrolidinyl, piperazinyl, morpholinyl, thiomorpholinyl and aryl, and is substituted with any one or more independently selected from the group consisting of C 1-12 alkyl is methoxy(ethoxy) 1-3 , hydroxy(ethoxy) 1-3 , di(C 1-4 alkyl)amino, C 1-4 alkyl, cycloC 1-3A group consisting of alkyl, pyrrolidinyl, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, and aryl.

[0111] In some embodiments, each R 5 is H, C 1-12 alkyl, C 2-12 alkenyl, C 4-12 dialkenyl and C 6-12 trialkenyl, independently selected from the group consisting of, C 1-12 alkyl is methoxy(ethoxy) 1-2 hydroxy(ethoxy) 1-2 dimethylamino, methylamino, amino, cyclo C 5-7 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, aryl and methoxy, and may be substituted with any one or more independently selected from the group consisting of.

[0112] In some embodiments, each R 5 is H, C 1-12 alkyl, C 2-12 alkenyl, C 4-12 dialkenyl and C 6-12 trialkenyl, independently selected from the group consisting of, C 1-12 alkyl is methoxy(ethoxy) 1-2 hydroxy(ethoxy) 1-2 dimethylamino, methylamino, amino, cyclo C 5-7 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, and aryl, and is optionally substituted with any one or more independently selected from the group consisting of.

[0113] In some embodiments, each R 5 is H, C 1-12 alkyl and C 4-12Independently selected from the group consisting of dialkenyl, wherein C 1-12 alkyl is methoxy(ethoxy) 1-2 , hydroxyl(ethoxy) 1-2 , dimethylamino, methylamino, amino, cyclo C 5-7 alkyl, pyrrolidinyl, 1-(3-propyl group)piperidine and methoxy, and is optionally substituted with any one or more independently selected from the group consisting of.--

[0114] In some embodiments, each R 5 is H, C 1-12 alkyl and C 4-12 dialkenyl, wherein C 1-12 alkyl is methoxy(ethoxy) 1-2 , hydroxyl(ethoxy) 1-2 , dimethylamino, methylamino, amino, cyclo C 5-7 alkyl, pyrrolidinyl and 1-(3-propyl group)piperidine, and is optionally substituted with any one or more independently selected from the group consisting of.--

[0115] As described above, n in formula IVb is 1 to 3. In some embodiments, n is 1 or 2, that is, the heterocyclic ring of IVb is 6- or 7-membered. In some embodiments, n is 2, that is, the heterocyclic ring of IVb is 7-membered.

[0116] In some embodiments, the compound is any one of the formulas defined in claim 21.

[0117] To avoid misunderstanding, when the compound is of formula I, it can be any one of formulas Ia1 to Id2. For example, when the compound is of formula I and A-D is of formula Ia, the compound can be any one of formulas Ia1 to Ia65, for example Ia1 to Ia47; when the compound is of formula I and A-D is of formula Ib, the compound can be any one of formulas Ib1 to Ib11; when the compound is of formula I and A-D is of formula Ic, the compound can be any one of formulas Ic1 to Ic23, for example Ic1 to Ic19; when the compound is of formula I and A-D is of formula Id, the compound can be of formula Id1 or Id2.

[0118] When the compound is of formula II, it can be any one of formulas II1 to II4, for example of formula II1.

[0119] When the compound is of formula III, it can be any one of formulas IIIa1 to IIIb9. For example, when the compound is of formula III and A-G is of formula IIIa, the compound can be any one of formulas IIIa1 to IIIa9; when the compound is of formula III and A-G is of formula IIIb, the compound can be any one of formulas IIIb1 to IIIb9. When the compound is of formula IV, it can be any one of formulas IVa1 to IVb3. For example, when the compound is of formula IV and C(O)-J is of formula IVa, the compound can be any one of formulas IVa1 to IVa18, for example IVa1 to IVa15; when the compound is of formula IV and C(O)-J is of formula IVb, the compound can be any one of formulas IVb1 to IVb3.

[0120] In some embodiments, the compounds of the invention are in the form of a pharmaceutically acceptable salt, i.e., the compounds can be isolated or prepared in the form of a pharmaceutically acceptable salt. The term "pharmaceutically acceptable salt" is intended to define a salt that can be administered to a patient or used in a pharmacy. Pharmaceutically acceptable salts can be prepared by reacting the compound with a suitable acid such as hydrogen chloride, hydrogen bromide, hydrogen iodide, sulfuric acid, phosphoric acid, acetic acid, trifluoroacetic acid, benzenesulfonic acid, propionic acid, glycolic acid, maleic acid, malonic acid, methanesulfonic acid, fumaric acid, succinic acid, tartaric acid, citric acid, benzoic acid and ascorbic acid. Alternatively, the compounds of the invention can be isolated as a pharmaceutically acceptable salt. As described above, when A-D (of formula I) is Ic or Id, A and R 3 or R 4 The nitrogen atom bonded to is positively charged. Thus, when A-D is Ic or Id, the resulting compound is a cation, and the positive charge of the cation is stabilized by a counterion (anion) to form a salt. The counterion can be pharmaceutically acceptable or the counterion can be exchanged with a pharmaceutically acceptable counterion, and the resulting compound is a pharmaceutically acceptable salt. An overview of pharmaceutical salts is provided by P H Stahl and C G Wermuth in Handbook of Pharmaceutical Salts: Properties, Selection and Use, Weinheim / Zurich: Wiley-VCH / VHCA, 2nd Revised Edition, 2011. When the compound is a cation, it can be stabilized by one or more of the anions described in this review.

[0121] The compounds of the present invention may exhibit tautomerism. All tautomers and mixtures thereof are included within the scope of the present invention. The compounds may exist in different stereoisomeric forms. All stereoisomers, including enantiomers and racemic mixtures, and mixtures thereof are included within the scope of the present invention. The individual stereoisomers of the compounds of the present invention, i.e., compounds containing less than 5% of other stereoisomers, less than 2% or less than 1% (e.g., less than 1%), are included. Mixtures of stereoisomers in any proportion, for example, racemic mixtures containing substantially equal amounts of two enantiomers, are also included in the present invention.

[0122] Diastereoisomers can be separated using conventional techniques, such as chromatography or fractional crystallization. The various stereoisomers can be isolated by separation of a racemic or other mixture of the compounds using conventional techniques, such as fractional crystallization or HPLC techniques. Alternatively, by reaction of a suitable optically active starting material under conditions that do not cause racemization or epimerization of the desired optical isomer, or by derivatization with, for example, a homochiral acid followed by separation of the diastereomeric esters by conventional means (e.g., HPLC, chromatography on silica).

[0123] Also included are solvates and isotopically enriched compounds of the present invention. Isotopically enriched compounds are identical to those described herein, except that an amount of the compound has an isotope of an element in greater abundance than is found in nature. Such isotopes by which the compounds of formula I can be enriched include, for example, specific isotopes of hydrogen, carbon, nitrogen, oxygen, sulfur, fluorine and chlorine, for example, 2 H, 3 H, 13 C, 14 C, 15 N, 18 O, 17 O, 35 S, 18 F, and 36 Cl.

[0124] According to that second aspect, the present invention provides a composition comprising one or more compounds (generally one compound) of the first aspect and a pharmaceutically acceptable excipient. A broad overview of pharmaceutically acceptable excipients is provided in R C Rowe, P J Sheskey and M E Quinn, The Pharmaceutical Press, Handbook of Pharmaceutical Excipients, 6 th Edition, published by The Pharmaceutical Press, London, UK in 2009. Any suitable pharmaceutically acceptable excipient described within the literature is within the scope of the present invention.

[0125] Pharmaceutically acceptable excipients can be included in the composition for the purpose of enhancing the activity of the compound, such as by promoting long-term stabilization of the compound, bulking of solid formulations (often referred to as bulking agents, fillers, or diluents), or its absorption in the body, reducing its viscosity, or increasing its solubility. Excipients can also enhance the in vitro stability of the compound, such as preventing denaturation or aggregation. Alternatively, excipients can be used to make the compound more appealing to the patient, for identification purposes or, for example, by improving its taste, odor and / or appearance. Typically, excipients make up the majority of the composition. Excipients include diluents or fillers, binders, disintegrants, lubricants, colorants and preservatives. Diluents or fillers are inert components that can affect the chemical and physical properties of the final composition. When the dosage of the compound of the present invention is low, more diluent is required to produce a composition suitable for practical use. When the dosage of the compound of the present invention is high, less diluent is required.

[0126] Binders add cohesiveness to the powder to form granules that can form tablets. The binder must also cause the tablet to disintegrate upon ingestion so that the compound of the present invention can dissolve. Disintegration of the composition after administration can be facilitated by the use of disintegrants.

[0127] Particularly mentioned are compositions suitable for use as disinfectants, such as compositions suitable for use as additives to contact lens solutions, etc., which are suitable for use in the prevention of microbial infections. Modern contact lens solutions typically contain antibacterial agents, surfactants, chelating agents, lubricants and propylene glycol (see, for example, Jones, Land Senchyna, MOptometry in Practice, 8, 2007, 45-56). According to a particular embodiment of the second aspect, the pharmaceutical composition is suitable for use as a contact lens solution. In some embodiments, the composition further comprises a pharmaceutically acceptable surfactant, chelating agent, lubricant and propylene glycol.

[0128] The antibacterial agent disinfects the lens so that it is safe to insert into the eye and preserves the solution so that it is safe to use after exposure to the environment. Antibacterial agents are typically effective against a variety of pathogens and are selective so as to avoid damage to eye tissue. In many cases, the antibacterial agent is any one or combination selected from the group consisting of hydrogen peroxide, polyhexamethylene biguanide, polyquaternium-1, alexidine, and amidoamine. The compounds of the present invention can be included in contact lens solutions in addition to or as an alternative to one or more of the typically used antibacterial agents.

[0129] Surfactants typically act as surfactants or detergents and are included in contact lens solutions to remove debris and deposits released from the contact lens by forming micelles in combination with these. Surfactants also act to increase the wettability of hydrophobic surfaces, so that when the contact lens is formed from a hydrophobic material such as silicone hydrogel, the hydrophobic surface can come into better contact with the contact lens solution.

[0130] Chelating agents are typically included in contact lens solutions and can act synergistically with other components of the solution to improve the effectiveness of disinfection or can assist in the removal of debris and deposits such as proteins.

[0131] Viscosifying agents are agents that protect and lubricate mucosal surfaces and are topically applied to the eye to relieve dryness and irritation, usually water-soluble polymers. Demulcents are typically included in contact lens solutions, for example, to improve comfort by modifying the lens surface. Propylene glycol is typically included in contact lens solutions to enhance moisture retention on the surface of hydrogel lenses.

[0132] Examples of surfactants, chelating agents, and viscosifying agents, as well as additional components suitable for inclusions in contact lens solutions, are described in Jones, Land Senchyna, M., 2007, supra.

[0133] To avoid misunderstanding, the embodiments described herein with respect to the compounds defined in the first aspect of the invention are applied to the second aspect with the necessary modifications. For example, one or more compounds of the second aspect can be any of the formulas defined herein.

[0134] As described above, the inventors have found that the compounds of the present invention can bind to DNA and RNA and are thus known as nucleic acid binders (NABs). Thus, the compounds of the present invention can substitute or inhibit the binding of enzymes or regulatory proteins to DNA and RNA. Enzymes that may be mentioned in this regard include those required for replication (and thus provide the effect of inhibiting DNA or RNA replication), as well as those involved in transcription (and thus provide the effect of inhibiting the expression of specific peptides (proteins, enzymes, etc.)). The affinity for DNA or RNA can be measured by techniques known to those skilled in the art, such as capillary electrophoresis. Furthermore, the affinity for a specific section of DNA or RNA can be determined by techniques known to those skilled in the art, such as the RNA footprinting method.

[0135] Due to their ability to inhibit DNA and / or RNA replication, the compounds of the present invention are useful in the treatment of diseases that rely on DNA or RNA replication for their growth. Such diseases include microbial infections and cancer. Such treatments can be particularly useful when the patients suffering from such diseases are immunocompromised. A third aspect of the present invention provides a compound of the first aspect or a composition of the second aspect for use as a medicament.

[0136] The fourth aspect of the present invention provides a compound of the first aspect or a composition of the second aspect for use in the treatment of any one or more selected from the group consisting of viral infections, bacterial infections, fungal infections, parasitic infections and cancer. The fifth aspect of the present invention provides a method of treating any one or more selected from the group consisting of viral infections, bacterial infections, fungal infections, parasitic infections and cancer, said method comprising administering to a patient in need thereof an effective amount of a compound of the first aspect or a composition of the second aspect. According to another aspect of the present invention, there is provided the use of a compound of the first aspect or a composition of the second aspect in the manufacture of a medicament for use in the treatment of any one or more conditions selected from the group consisting of viral infections, bacterial infections, fungal infections, parasitic infections and cancer. To avoid misunderstanding, the embodiments described herein in relation to the first and second aspects of the present invention apply to these aspects with the necessary modifications. For example, the compound may be any one of the formulas defined herein and / or the composition may comprise one or more pharmaceutically acceptable excipients as described in the Handbook of Pharmaceutical Excipients (supra).

[0137] The genetic material of bacteria, fungi and parasites is DNA, while the genetic material of viruses is DNA or RNA.

[0138] Where the disease to be treated by the compounds of the present invention is an RNA virus infection, the virus causing the infection may comprise RNA which is single-stranded (ssRNA) or double-stranded (dsRNA). Examples of double-stranded RNA viruses include reovirus and rotavirus. Typically, the RNA within an RNA virus is single-stranded.

[0139] A single-stranded RNA virus can be positive-sense, negative-sense or ambisense. Positive-sense RNA viruses act in a manner similar to messenger RNA (mRNA) and contain RNA that can be immediately translated by the host cell. Examples of plus-sense single-stranded RNA viruses include coronaviruses, rhinoviruses, polioviruses, hepatitis C and E viruses, and Zika virus.

[0140] Negative-sense RNA viruses contain RNA that must first be converted to positive-sense RNA by an RNA-dependent RNA polymerase, after which they are translated by the host cell. Examples of negative-sense single-stranded RNA viruses include influenza virus, measles virus, mumps virus, rabies virus and Ebola virus. Ambisense RNA viruses are similar to negative-sense viruses but contain at least one ambisense RNA segment that carries both positive-sense and negative-sense RNA, and the RNA virus may or may not be segmented. The genome of an RNA virus is often divided into separate parts, i.e., separate RNA molecules, in which case it is said to be segmented. Each segment often encodes just one protein.

[0141] When the disease treated by the compounds of the present invention is a DNA virus infection, the virus causing the infection may contain DNA that is double-stranded (dsDNA) or single-stranded (ssDNA), and the ssDNA virus typically acts in a manner similar to mRNA and has a positive-sense genome containing DNA that can be immediately translated by the host cell. When the DNA within a DNA virus is ssDNA, it is typically in the positive sense and is often a circular genome that replicates via rolling circle replication. However, typically, the DNA within a DNA virus is double-stranded. Examples of double-stranded DNA viruses include adenoviruses (e.g., Titi herpes), herpesviruses (e.g., Macacine herpesvirus), and polyomaviruses.

[0142] RNA or DNA viruses can be enveloped by a protein, i.e., a viral envelope. This protects the genetic material within the virus and is typically derived from a portion of the host cell membrane. Examples of enveloped RNA viruses include coronaviruses, hepatitis C virus, Zika virus, influenza virus, measles virus, and rabies virus. An example of an enveloped DNA virus is herpesvirus.

[0143] In some embodiments, the viral infection is caused by any one of the group consisting of respiratory syncytial virus, human rhinovirus, human influenza virus, influenza virus, such as influenza virus A and B, norovirus, dengue virus, yellow fever virus, West Nile virus, Zika virus, Rift Valley fever virus, African swine fever virus, Japanese encephalitis virus, Nipah virus, coronavirus, such as SARS-CoV-2, adenovirus, such as Titi adenovirus, herpesvirus, such as Macacine herpesvirus, and polyomavirus. Typically, the viral infection is caused by an RNA virus.

[0144] In some embodiments, the bacterial infection is caused by any one of the group consisting of Staphylococcus aureus, Enterococcus, Streptococcus, Clostridium, Corynebacterium, Mycobacterium tuberculosis and non-tuberculous mycobacteria, Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa, Helicobacter pylori, Campylobacter, Salmonella, Neisseria gonorrhoeae, Haemophilus influenzae, and Shigella.

[0145] In some embodiments, the fungal infection is Candida albicans, Candida auris, Candida glabrata, Candida parapsilosis, Candida krusei, Candida guilliermondii, Cryptococcus neoformans, Cryptococcus gattii, Aspergillus gattii, Aspergillus fumigatus, Aspergillus flavus, Rhizopus arrhizus, Fusarium oxysporum, Fusarium solani, Scedosporium prolificans, Lomentospora prolificans, Blastomyces dermatitidis, Paecilomyces variotii, Mucor spp, Pneumocys.

[0146] In some embodiments, the parasitic infection is caused by any one of the group consisting of Trypanosoma brucei brucei gambiense, Trypanosoma brucei brucei rhodesiense, Trypanosoma congolense, Trypanosoma equiperdum, Trypanosoma evansi, Trypanosoma cruzi, Trichomonas vaginalis, Toxoplasma gondii, Plasmodia spp, Leishmania spp., and Acanthamoeba spp.

[0147] Due to the different modes of action exhibited by the compounds of the present invention compared to many conventional antibacterial agents, the compounds of the present invention can be particularly useful in the treatment of microbial infections when the infectious agent is resistant to one or more antibacterial agents having different modes of action. Accordingly, provided herein is also a method of treating a microbial infection that is resistant to one or more antibacterial agents that do not act by inhibiting DNA and / or RNA replication of the microorganism causing the infection, the method comprising administering to a patient having the infection a therapeutically effective amount of a compound of the first aspect or a composition of the second aspect of the present invention.

[0148] The compounds of the present invention can be used in combination with one or more other compounds or treatment regimens used to treat diseases that are dependent on DNA and / or RNA replication for their growth. Accordingly, provided herein is also a method of treating a disease that is dependent on DNA and / or RNA replication for its propagation (e.g., a microbial infection or cancer), the method comprising administering to a patient a therapeutically effective amount of a compound of the first aspect or a composition of the second aspect of the present invention in combination with one or more other agents known to be effective in treating the disease.

[0149] As used herein, the term "in combination with" includes the administration of other agents known to be effective in the treatment of a disease before, during, and / or after the administration of the compound or composition of the present invention. When two or more other agents are administered, the term also includes the administration of the different other agents at different times compared to the administration of the compound or composition of the present invention.

[0150] Agents known to be effective in treating diseases that are dependent on DNA and / or RNA replication for their growth (e.g., antibacterial or anti-cancer agents) include those listed under the headings relevant to "Martindale: The Complete Drug Reference", 40 th th Edition, Pharmaceutical Press, London (2020).

[0151] When the compounds or compositions of the present invention are administered to a patient in combination with one or more other agents known to be effective in treating diseases that depend on DNA and / or RNA replication for their growth, the compounds or compositions of the present invention and the other agents can be administered separately or, preferably, as a single composition. Accordingly, the present specification also provides combination products comprising a formulation containing the compound of the present invention; and a formulation containing one or more other agents known to be effective in treating diseases that depend on DNA and / or RNA replication for their growth.

[0152] The combination product may contain the compound of the present invention and one or more other agents as separate components or may be combined in a single formulation. When the compound of the present invention and one or more other agents are separate components, the combination product is a kit of parts.

[0153] The compounds and compositions of the present invention can be administered orally, subcutaneously, intravenously, intraarterially, transdermally, intranasally, by inhalation, or by any other enteral or parenteral route. The compounds and compositions are typically administered in the form of a pharmaceutical formulation containing the compound of the present invention, for example, as a free base or a non-toxic organic or inorganic acid addition salt, in a pharmaceutically acceptable dosage form. Depending on the disease being treated and the patient, as well as the route of administration, the compounds and compositions of the present invention can be administered in various doses. The appropriate daily dose of the compound of the present invention in human therapeutic treatment is about 0.1 to about 100 mg / kg, for example 0.15 to about 50 mg / kg.

[0154] The most effective mode of administration and dosage regimen for the compounds and compositions of the present invention depend on several factors including the particular condition being treated, the degree and localization of that condition in the patient being treated, and the health status and their response of the patient to the compound being administered. Accordingly, the dosage of the compound of the present invention should be adjusted to suit the individual patient. Methods for determining the appropriate dosage for an individual patient are known to those skilled in the art.

[0155] In a sixth aspect, the present invention provides the use of a compound of the first aspect or a composition of the second aspect in the binding of RNA or DNA, wherein the binding is ex vivo or in vitro. To avoid misunderstanding, the embodiments described herein in connection with the first and second aspects of the present invention are applied to the sixth aspect with the necessary modifications. For example, the compound may be any one of the formulas defined herein, and / or the composition may include one or more of the pharmaceutically acceptable excipients described in the Handbook of Pharmaceutical Excipients (supra).

[0156] In a further aspect, there is provided a method of binding a compound of the first aspect or a composition of the second aspect to RNA or DNA, the method comprising contacting the compound or composition with RNA or DNA. The compound or composition can be contacted with RNA or DNA ex vivo, in vitro or in vivo. Typically, the contacting is performed ex vivo or in vitro.

[0157] The compounds of the present invention can have particularly high affinity for at least one DNA and / or RNA sequence. When binding to at least one DNA and / or RNA oligomer or polymer, the compound has a dissociation constant of less than about 10 -5 M, less than about 10 -6 M (e.g., about 10 -7 M) or less than about 10 -8 M. In this regard, the dissociation constant can be measured under conditions known to those skilled in the art, e.g., in the presence of a buffer (e.g., a buffer that stabilizes a pH of about 7.5, e.g., a borate (e.g., about 0.02 M) or Tris / HCl (e.g., about 0.01 M) buffer), in water at room temperature (e.g., room temperature or about 20°C), and at a DNA or RNA concentration of about 10 to about 30 mM (e.g., about 20 mM). Alternatively, the dissociation constant can be estimated by comparing the binding affinity of the compound for a set DNA or RNA sequence with the binding affinity of a well-known compound for the same sequence.

[0158] The compounds of the present invention can also be used in various assay methods based on DNA or RNA binding. For example, compounds that bind to the minor groove of DNA have the ability to stabilize DNA double-strands and stabilize a perfectly matched (with respect to base pairs) DNA double-strand to a much greater extent than a mismatched DNA double-strand, thereby making it possible to facilitate the discrimination between a perfectly matched double-strand and a mismatched double-strand (e.g., with respect to the melting temperature of the double-strand).

[0159] Accordingly, according to a further aspect of the present invention, there is provided a method of stabilizing a DNA or RNA double-strand formed between a first and a second single-strand of DNA or RNA, respectively, the method comprising contacting the DNA or RNA double-strand with a compound of the present invention.

[0160] Furthermore, there is also provided a method of enhancing the difference in melting temperature between a first and a second DNA or RNA double-strand, each DNA or RNA double-strand being formed from a first single-strand of DNA or RNA, respectively, and being the same in each of the DNA or RNA double-strands and the second single-strand of DNA or RNA, and being different in each of the double-strands. The first DNA or RNA double-strand may have a higher degree of base pair matching (e.g., may be perfectly matched) than a second DNA or RNA double-strand that may have at least one base pair mismatch.

[0161] Completely matched DNA or RNA double strands can be used with compounds that significantly stabilize them more than mismatched DNA or RNA double strands to reduce the level of "false positive" results in DNA or RNA hybridization assay techniques, for example, as described in US 6221589. The reduction in "false positive" results can be achieved by using more stringent conditions (e.g., higher wash temperatures) after the hybridization reaction in the presence of the double-strand stabilizing compound than are possible after the reaction in the absence of such a compound. Accordingly, a method of increasing the maximum temperature of washing after a DNA or RNA hybridization reaction, the method comprising providing a compound of the invention to the hybridization reaction mixture, is further provided herein. As used herein, the term "maximum temperature of washing after a DNA or RNA hybridization reaction" refers to the highest wash temperature possible that does not result in a substantial loss of "true positive" results (i.e., completely or most highly matched DNA or RNA double strands).

[0162] As used herein with respect to the above-described methods involving DNA or RNA double strands, the term "contacting" includes mixing a compound of the invention with a DNA or RNA double strand. However, the term also includes binding (e.g., covalently) a compound of the invention having functional groups that can be used to form suitable bonds to one or both of the single strands of DNA or RNA that form the double strand. Such "labeled" single strands of DNA or RNA can be used as primers, capture probes, or in many different assays (e.g., capture-detection assays, 5'-nuclease assays, and beacon assays).

[0163] The compounds of the present invention may also have fluorescence properties. The fluorescent compounds of the present invention may be useful in various assay methods based on DNA or RNA binding that involve or require fluorescence. Accordingly, according to a further aspect of the present invention, there is provided a method for detecting an exemplary kit or double-stranded RNA in a sample, the method comprising contacting the compound of the present invention with the sample and comparing the fluorescence of the compound contacted with the sample to the fluorescence of the isolated compound, wherein a change in fluorescence indicates the presence of DNA or RNA in the sample.

[0164] In this embodiment of the present invention, the change in fluorescence can be, for example, a change in the wavelength of light emitted by the compound of the present invention, a change in the wavelength of light absorbed by the compound, or a change in the intensity of light emitted by the compound. Further, an exemplary kit or dsRNA can also be labeled with a fluorophore. In such labeled methods (and even in methods not so labeled), an exemplary kit or double-stranded RNA can act as a donor or acceptor in a "FRET" type assay for detecting the presence of an exemplary kit or double-stranded RNA.

[0165] In another aspect of the present invention, there is provided a method for detecting and visualizing an exemplary kit or double-stranded RNA in a sample, the method comprising contacting the sample with the compound of the present invention and irradiating the sample with ultraviolet light. In this embodiment of the present invention, the sample can be obtained from an agarose gel electrophoresis experiment or from a DNA or RNA microarray.

[0166] Any discussion in this specification of documents, acts, materials, devices, articles, etc. should not be construed as an admission that any or all of these matters form part of the prior art base or are common general knowledge in the field related to the present disclosure that existed prior to the priority date of each claim of this application.

[0167] Those skilled in the art will understand that numerous modifications and / or alterations can be made to the invention described herein without departing from the scope of the invention as described. Therefore, this embodiment is for illustrative purposes only and is not limiting, and is not limited to the scope described in the embodiment. Those skilled in the art should understand that this embodiment can be read alone or in combination, and can be combined with any one or combination of the features described herein.

[0168] The subject matter of each patent and non-patent document cited herein is incorporated herein by reference in its entirety.

[0169] The present invention can be further understood with reference to the following non-limiting clauses:

[0170] 1. A compound of any one of Formulas I, II, III, and IV:

Chemical formula

Chemical formula

Chemical formula

Chemical formula

[0171] 2. A compound according to item 1, wherein the compound forms a pharmaceutically acceptable salt.

[0172] 3. Q a and Q b is N(C 1-6 alkyl) 2 halo C 1-6 alkyl, cyano, C 1-6 alkyl, C 1-6 alkyl, C 1-6 alkyl) 2 halo C 1-6 alkyl, cyano, C 1-6 alkyl and C 1-6 alkoxy, and optionally substituted with any one or a combination selected from the group consisting of halo, for example, N(C a alkyl) b halo C

[0173] 4. Q a and Q b is N(C 1-4 alkyl) 2 halo C 1-4 alkyl, cyano, C 1-4 alkyl, C 1-4 alkyl, C 1-4 alkyl) 2 halo C 1-4 alkyl, cyano, C 1-4 alkyl and C 1-4 alkoxy, and optionally substituted with any one or a combination selected from the group consisting of halo, for example, N(C a alkyl) b halo C

[0174] 5. Q a and Qb is, for example, Q a and Q b is N(CH 3 ) 2 , optionally substituted with any one or a combination selected from the group consisting of halomethyl, cyano, methyl, methoxy group and fluoro, for example, N(CH 3 ) 2 , optionally substituted with any one or a combination selected from the group consisting of halomethyl, cyano, methyl and methoxy group, the compound according to claim 1 or 2.

[0175] 6. Q a is optionally substituted phenyl, quinolinyl, benzoxadiazolyl, naphthalenyl, benzothiazolyl group, isoquinolinyl, thiazolyl group, pyridinyl, pyrimidinyl, thiophenyl, pyridazinyl, phthalazinyl, imidazolyl and pyrrolyl, the compound according to any one of claims 1 to 5.

[0176] 7. Q a is optionally substituted phenyl, quinolinyl, benzoxadiazolyl, naphthalenyl and benzothiazolyl, the compound according to any one of claims 1 to 5.

[0177] 8. Q b is monocyclic and the compound according to any one of claims 1 to 7.

[0178] 9. Q b is optionally substituted phenylene and pyridinediyl, the compound according to any one of claims 1 to 7. 10. Q b is unsubstituted and the compound according to any one of claims 1 to 9.

[0179] 11. Each R is independently selected from the group consisting of C 1-4 and H, the compound according to any one of claims 1 to 10.

[0180] 12. The compound according to any one of items 1 to 10, wherein each R is independently selected from the group consisting of methyl and H.

[0181] 13. The compound according to any one of items 1 to 12, wherein A is C 1-6 alkylene.

[0182] 14. The compound according to any one of items 1 to 12, wherein A is C 2-5 alkylene.

[0183] 15. The compound according to any one of items 1 to 14, wherein Z is selected from the group consisting of O, CH 2 , N(CH 3 ), and S. -

[0184] 16. Each R 2 is independently selected from the group consisting of H, C 1-9 alkyl, C 1-9 alkoxy, C 2-9 alkenyl, C 4-9 dialkenyl, and C 6-9 trialkenyl, where C 1-9 alkoxy, C 2-9 alkenyl, C 4-9 dialkenyl, and C 6-9 trialkenyl are optionally substituted with any one or more independently selected from the group consisting of phenyl, 1-(C 1-6 alkyl)piperazinyl, tetrahydropyranyl, N(C 1-6 alkyl) 2 , methoxy(ethoxy) 1-3 , hydroxy(ethoxy) 1-3 , thiomorpholinyl, C 1-9 alkoxy, and halo, and where each R 2 is independently selected from the group consisting of H, C 1-9 alkyl, C 1-9 alkoxy, C 4-9 dialkenyl, and C 6-9 trialkenyl, phenyl, 1-(C 1-6(alkyl)piperazinyl, tetrahydropyranyl, N(C 2-9 (alkyl)( 2 , methoxy(ethoxy)( 1-3 and hydroxy(ethoxy)C( 1-9 is independently selected from any one or more of the group consisting of,( 1-3 alkyl, C( 1-3 alkenyl, C( 4-9 dialkenyl and C( 6-9 trialkenyl may be optionally substituted. ( (

[0185] ( 17. Each R( 2 is independently selected from the group consisting of H, C( 1-9 alkyl and C( 1-9 alkoxy, wherein C( 1-9 alkyl and C( 1-9 alkoxy are optionally substituted with any one or more independently selected from the group consisting of phenyl, 1-(methyl)piperazinyl, tetrahydropyranyl, N(C( 1-3 (alkyl)( 2 , methoxy(ethoxy)( 1-2 , hydroxy(ethoxy)( 1-2 , thiomorpholinyl, methoxy and fluoro, for example, each R( 2 is independently selected from the group consisting of H, C( 1-9 alkyl and C( 1-9 alkoxy, wherein C( 1-9 alkyl and C( 1-9 alkoxy are optionally substituted with any one or more independently selected from the group consisting of phenyl, 1-(methyl)piperazinyl, tetrahydropyranyl, N(C( 1-3 (alkyl)( 2 , methoxy(ethoxy)( 1-2 and hydroxy(ethoxy)( 1-2 and is optionally substituted with any one or more of the group consisting of, a compound according to any one of items 1 to 15. ( (

[0186] ( 18. Each R( 3 is independently C( 1-20 alkyl, a phenyl group, 1-(methyl)piperazinyl, tetrahydropyranyl, N(C( 1-3 (alkyl)2 、methoxy(ethoxy) 1-2 、and hydroxyl(ethoxy) 1-2. The compound according to any one of items 1 to 17, which is optionally substituted with any one or more independently selected from the group consisting of

[0187] 19. Each R 3 is independently, methoxy(ethoxy) 1-2 、and hydroxyl(ethoxy) 1-2 The compound according to any one of items 1 to 17, which is optionally substituted with any one or more independently selected from the group consisting of C 1-20 alkyl

[0188] 20. R 4 is a phenyl group, 1-(methyl)piperazinyl, tetrahydropyranyl, N(C 1-3 alkyl) 2 、methoxy(ethoxy) 1-2 、and hydroxyl(ethoxy) 1-2 The compound according to any one of items 1 to 19, which is optionally substituted with any one or more independently selected from the group consisting of C 2-20 alkyl

[0189] 21. R 4 is C 2-10 alkyl

[0190] 22. The compound according to any one of items 1 to 17, wherein A-D is selected from the group consisting of formula Ia and Ib

[0191] 23. The compound according to any one of items 1 to 22, wherein E is C 4-6 alkylene

[0192] 24. Each R 1 is independently selected from the group consisting of C 1-4 and H

[0193] 25. Each R1 The compound according to any one of claims 1 to 23, wherein R is independently selected from the group consisting of methyl and H.

[0194] 26. The compound according to any one of claims 1 to 25, wherein A-G is of formula IIIa.

[0195] 27. For the compound of claim 1, each R 5 is H, C 1-12 alkyl, C 2-12 dialkenyl and C 6-12 trialkenyl, independently selected from the group consisting of, wherein C 2-12 alkenyl, C 4-12 dialkenyl and C 6-12 trialkenyl is methoxy(ethoxy) 1-3 , dialkylamino, C 1-4 , cycloCC 4-12 alkyl, piperidinyl, piperazinyl, morpholinyl, and aryl, independently selected from the group consisting of, C 1-12 alkyl is methoxy(ethoxy) 1-3 , hydroxy(ethoxy) 1-3 , di(C 1-4 )amino, C 1-4 alkylamino, aminoC 1-3 alkyl, cycloCC 1-4 alkyl, pyrrolidinyl, independently selected from the group consisting of, 1-(3-propyl)piperidine, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, aryl and C 1-3 alkoxy H, C 1-12 alkyl, C 2-12 dialkenyl and C 6-12 trialkenyl, a group consisting of, wherein C 2-12 alkenyl, 1-6 dialkenyl and 3-8 trialkenyl is methoxy(ethoxy) 1-3 , di(alkyl)amino, C 1-4 alkylamino, cycloCC 4-12Optionally substituted with any one or more selected from the group consisting of alkyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl and aryl, C 1-12 alkyl is methoxy(ethoxy) 1-3 , hydroxy(ethoxy)C 4-12 , di(C 6-12 )amino, C 1-4 alkylamino, aminoC 3-8 alkyl, cycloCC 1-4 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, optionally substituted with any one or more selected from the group consisting of 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine.

[0196] 28. Each R 5 is independently selected from the group consisting of H, C 1-12 alkyl, C 2-12 alkenyl, C 4-12 dialkenyl and C 6-12 trialkenyl, where C 1-12 alkyl is methoxy(ethoxy) 1-2 , hydroxy(ethoxy) 1-2 , dimethylamino, methylamino, cycloC 5-7 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, aryl and C 1-3 alkoxy, for example, each R 5 is independently selected from the group consisting of H, C 1-12 alkyl, C 2-12 alkenyl, C 4-12 dialkenyl and C 6-12 trialkenyl, C 1-12 alkyl is methoxy(ethoxy) 1-2 , hydroxy(ethoxy) 1-2 , dimethylamino, amino, cycloC 5-7 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine and aryl.

[0197] 29. Each R 5 is independently selected from the group consisting of H, C 1-12 alkyl and C 4-12 diallyl, where C 1-12 alkyl is methoxy(ethoxy) 1-2 , hydroxy(ethoxy) 1-2 , dimethylamino, methylamino, amino, cyclo C 5-7 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine and methoxy, and is optionally substituted with any one or more independently selected from the group consisting of, for example, each R 5 is independently selected from the group consisting of H, C 1-12 alkyl and C 4-12 diallyl, where C 1-12 alkyl is methoxy(ethoxy) 1-2 , hydroxy(ethoxy) 1-2 , dimethylamino, methylamino, amino, cyclo C 5-7 alkyl, pyrrolidinyl and 1-(3-propyl)piperidine, and is optionally substituted with any one or more independently selected from the group consisting of. The compound according to any one of items 1 to 26.

[0198] 30. The compound according to any one of items 1 to 29, where n is 1 or 2.

[0199] 31. The compound according to item 1, which is any one of formulas Ia1 to IVb3 (described in claim 21).

[0200] 32. A composition comprising one or more compounds according to any one of items 1 to 31 and a pharmaceutically acceptable excipient.

[0201] 33. The compound according to any one of items 1 to 31 or the composition according to item 32 for use as a medicament.

[0202] 34. A compound according to any one of claims 1 to 31 or a composition according to claim 32 for use in the treatment of any one or more conditions selected from the group consisting of viral infection, bacterial infection, fungal infection, parasitic infection and cancer.

[0203] 35. Use of a compound according to any one of claims 1 to 31 or a composition according to claim 32 in the manufacture of a medicament for use in the treatment of any one or more conditions selected from the group consisting of viral infection, bacterial infection, fungal infection, parasitic infection and cancer.

[0204] 36. A method of treatment for any one or more selected from the group consisting of viral, bacterial, fungal, and parasitic infections, and cancer, comprising administering to a patient in need thereof an effective amount of a compound as defined in any one of claims 1 to 31 or a composition as defined in claim 32.

[0205] 37. A compound or composition for use according to claim 34, use according to claim 35, or method according to claim 36, wherein: (i) the viral infection is caused by any one of the group consisting of respiratory syncytial virus, human rhinovirus, human influenza virus, influenza virus, such as influenza virus A and B, norovirus, dengue virus, yellow fever virus, West Nile virus, Zika virus, Rift Valley fever virus, African swine fever virus, Japanese encephalitis virus, Nipah virus, coronavirus, such as SARS-CoV-2, adenovirus, such as Titsal adenovirus, herpes virus, such as Macacine herpes virus, and polyomavirus; (ii) the bacterial infection is caused by any one of the group consisting of Staphylococcus aureus, Enterococcus, Streptococcus, Clostridium, Corynebacterium, Mycobacterium tuberculosis and non-tuberculous mycobacterium, Enterobacteriaceae, Acinetobacter baumannii, Pseudomonas aeruginosa, Helicobacter pylori, Campylobacter genus, Salmonella, Neisseria gonorrhoeae, Haemophilus influenzae, and Shigella genus; (iii) The fungal infection is caused by any one of the group consisting of Candida albicans, Candida auris, Candida parapsilosis, Candida krusei, Candida guilliermondii, Cryptococcus neoformans, Cryptococcus gattii, Aspergillus fumigatus, Aspergillus flavus, Rhizopus arrhizus, Fusarium oxysporum, Fusarium solani, Scedosporium prolificans, Lomentospora prolificans, Blastomyces dermatitidis, Paecilomyces variotii, Mucor species, Pneumocystis jirovecii, Histoplasma capsulatum, Coccidioides immitis and Coccidioides posadasii; (iv) The parasitic infection is caused by any one of the group consisting of Trypanosoma brucei brucei, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense, Trypanosoma congolense, Trypanosoma equiperdum, Trypanosoma evansi, Trypanosoma cruzi, Trichomonas vaginalis, Toxoplasma gondii, Plasmodia spp, Leishmania spp, and Acanthamoeba spp.

[0206] 38. Use of the compound according to any one of claims 1 to 31 or the composition according to claim 32 in the binding of RNA or DNA, wherein the binding is used ex vivo or in vitro.

Examples

[0207] (Experimental Examples) The present invention can be further understood with reference to the following examples.

[0208] (General Experimental Methods) Reagent Abbreviations: DMF, N,N-dimethylformamide; HBTU, 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate; TFA, trifluoroacetic acid; DIPEA, N,N-diisopropylethylamine; HATU, 2-(3H-[1,2,3]triazolo[4,5-b]pyridin-3-yl)-1,1,3,3-tetramethylisouronium hexafluorophosphate; MeOH, methanol; MeCN, acetonitrile; DMSO, dimethyl sulfoxide; Et 2 O, diethyl ether; THF, tetrahydrofuran

[0209] Purification Equipment: HPLC When indicated, the compound was purified using a Gilson PL C2250 equipped with a custom 5 μm particle size Nucleodur C18 (50x40~75 g) gravity-prepared column. Two solvent systems were used: Solvent A (water w / 0.1% TFA), Solvent B (acetonitrile w / 0.1% TFA). The initial gradient method used to optimize the purification was:

[0210]

Table 1-1

[0211] The gradient was optimized during each run to maximize separation, so it should be noted that the provided gradient method is only a guide. Fractions were analyzed by low-resolution mass spectrometry (LRMS), fractions with the desired material were combined, acetonitrile was removed using a Smart Evaporator, and it was ready for lyophilization. After re-injection, all final S-MGBs were determined to be >95% pure. With HPLC eluents containing TFA, all S-MGBs are isolated with TFA counterions as needed.

[0212] (Smartphone Evaporator) Acetonitrile was removed from the fractions by HPLC purification using BioChromato. Company Limited. Smartphone Evaporator C1. For this procedure, the sample was accommodated in a round-bottom flask of appropriate size.

[0213] (Freeze dryer) The sample contained in a round-bottom flask of appropriate size was frozen by immersion in liquid nitrogen before freeze-drying using an LTE Mini Lyotrap Freeze Dryer.

[0214] Characterization equipment: Low-resolution mass spectrometry (LRMS) The sample was dissolved in MeOH / H 2 O containing 0.1% formic acid. Low-resolution mass spectra were recorded using an Agilent Technologies 1200 series LC-MS instrument with a 6130 single quadrupole and dual electrospray and atmospheric chemical ionization sources. The LC traces were recorded at a wavelength of 254 nm at 1 mL / min using an Agilent poroshell 120, EC-C18 2.7 μm, 4.6×100 mm column. Two solvent systems were used for chromatographic separation: Method A using Solvent A (water containing 0.1% formic acid) and Solvent B (MeCN containing 0.1% formic acid); and Method B using Solvent C (water containing 5 mM ammonium acetate) and Solvent D (MeCN containing 5 mM ammonium acetate). Method A was used unless otherwise specified.

[0215]

Table 1-2

[0216] (High-resolution mass spectrometry (HRMS)) This was conducted at the NMSF of Sungkyunkwan University. The samples were solvated in MeCN and then diluted either in methanol (salt) or methanol + 30 mM ammonium acetate (neutral) for cations (to promote protonation and ammonium adduct formation rather than cationization), or in methanol (salt) or methanol + diethylamine (neutral) for anion analysis. The appropriately diluted samples were delivered at a flow rate of approximately 0.25 μL / min using an Advion Trivers NanoMate (nanoelectrospray). This inlet is used with a 96-well plate, corresponding transfer tip, and 400 nozzle spray tip. The applied nanoelectrospray settings include a spray voltage of 1.4 kV, a gas pressure of 0.4 psi, a transfer capillary temperature of 200 °C, and a transfer capillary voltage of 30 V. Mass spectrometric detection was performed in positive / negative ionization mode via a Thermo Scientific LTQ Orbitrap XL. Stock solutions of caffeine, MRFA (Met-Arg-Phe-Ala), and Ultramark 1621 were used for positive ions, and sodium dodecyl sulfate and sodium taurocholate were added to this solution for negative ions to externally calibrate the instrument daily. Internal calibration is achieved by the "lock mass" of known background ions. Spectra were recorded at a mass accuracy of <3 ppm RMS over an m / z temperature range of 150 - 2000 Da with a resolution of 100,000 (FWHM).

[0217] (Nuclear Magnetic Resonance Method) All of the synthesized compounds 1 1H NMR spectral data were recorded at 500 Hz using a Bruker DRX 500 spectrometer with the specified deuterated solvent and using Console Advance III HD and 4.0.7 Topspin software. Chemical shift values (δ) are expressed in parts per million (ppm). The following abbreviations are 1Used for the multiplicity of ¹H NMR signals: s (singlet), d (doublet), dd (doublet of doublets), dt (doublet of triplets), dddd (doublet of doublets), m (multiplet), t (triplet), td (triplet of doublets), and q (quartet). Coupling constants are listed as J values measured in Hz. The solvent reference was DMSO-d6 referenced at 2.50 1 ¹H 6 was.

[0218] (Infrared (IR)) IR spectra were measured on a Shimadzu IRAffinity-1S Fourier Transform Infrared spectrophotometer equipped with a single reflection ATR accessory.

[0219] (Definition of the structural elements of the compounds of the present invention) The final step in the synthesis of the compounds of the present invention is generally achieved by one of two routes: (i) coupling of a "head group dimer" to a "tail group dimer"; or (ii) direct coupling to the tail group of a "tetramer". Optionally, the compounds are further modified to produce other compounds of the present invention. [Chemical formula] Scheme 1: Resynthesis of typical compounds of the present invention.

[0220] (Synthesis of head group dimers) In most cases, the head group monomers were prepared according to literature procedures, but the synthesis and characterization of novel head group monomers are fully described. In most cases, the carboxylic acid formation of the head group monomers was prepared from the corresponding methyl esters.

[0221] 6-{(E)-2-[4-(Dimethylamino)phenyl]ethenyl}nicotinic acid Scott, Fraser Jet al, European Journal of Medicinal Chemistry, 2016, vol. 116, p. 116-125

[0222] 4-[(E)-2-(3-Quinolinyl)ethenyl]benzoic acid Anthony, Nahoum G.; et al, Journal of Medicinal Chemistry, 2007, vol. 50, # 24, p. 6116-6125

[0223] 4-[(E)-2-(2,1,3-Benzoxadiazol-5-yl)ethenyl]benzoic acid Scott, Fraser J, 2016, the above

[0224] (E)-4-(2-(Naphthalen-2-yl)vinyl)benzoic acid Anthony, Nahoum G, 2007, the above

[0225] 4-{(E)-2-[4-(Trifluoromethyl)phenyl]ethenyl}benzoic acid Scott, Fraser J, 2016, the above

[0226] 4-[(E)-2-(1,3-Benzothiazol-2-yl)ethenyl]benzoic acid Anthony, Nahoum G, 2007, the above 6-[(E)-2-(4-Methoxyphenyl)ethenyl]nicotinic acid Anthony, Nahoum G, 2007, the above

[0227] 4´-Methoxy-trans-stilbene-4-carboxylic acid This compound was prepared from its methyl ester and subsequently hydrolyzed.

[0228] Methyl 3-[(E)-2-(4-methoxyphenyl)ethenyl]benzoate To a solution of methyl 3-[(diethoxyphosphoryl)methyl]benzoate (1.02 g, 3.56 mmol) in THF (5 mL, dry) was added sodium hydride (0.212 g, 60%, 18.8 mmol) under a nitrogen atmosphere. 0 oAfter cooling to C, p-anisaldehyde (0.485 g, 3.56 mmol) was dissolved in THF (10 mL, dry), and carefully added dropwise with stirring. The reaction mixture was stirred at room temperature for 1 h and then quenched with water. After neutralization with dilute hydrochloric acid, the two layers were separated. The aqueous layer was extracted with ethyl acetate, the organic layers were combined, dried (MgSO 4 ), filtered, and the solvent was removed under reduced pressure. The product was purified using silica gel column chromatography to give a white solid (0.747 g, 78%), melting point 92-94 o °C. IR (centi -1 ) 1710, 158, 1467, 1440, 1267, 1161, 792, 744, 686 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 8.16 (1H, s), 7.91 (1H, d, J = 8.1 Hz), 7.86 (1H, d, J = 8.1 Hz), 7.55-7.20 (6H, m), 6.87 (1H, dd, J = 1.7 Hz, J = 8.0 Hz), 3.88 (3H, s), 3.80 (3H, s). 13C 17 1H 16 17O 3 268.1099 [M+H] + Calculated HRMS m / z for, found 268.1101 [M+H] +

[0229] 3-[(E)-2-(4-Methoxyphenyl)ethenyl]benzoic acid Methyl 3-[(E)-2-(4-methoxyphenyl)ethenyl]benzoate (0.740 mg, 2.75 mmol) was suspended in methanol (10 mL) and water (20 mL) to which a lithium hydroxide solution was added (0.199 g, 8.27 mmol) in water (10 mL) was added with stirring. The reaction mixture was heated under reflux for 4 h. First, the starting material dissolved and then a white precipitate appeared. The reaction mixture was cooled in an ice bath and then dilute hydrochloric acid was added dropwise with vigorous stirring to pH 2. The product as a white solid was filtered off, washed with water, and 60 oC (0.235 g, 34%) was dried under reduced pressure at a melting point of 195 - 198 °C. Infrared (centimeter -1 ) 1684, 1586, 1541, 1423, 1310, 1272, 961, 767, 687 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 8.12 (1H, s), 7.78 (1H, d, J = 7.6 Hz), 7.63 (1H, d, J = 7.6 Hz), 7.37 - 7.18 (7H, m), 6.83 (1H, dd, J = 1.7 Hz, J = 8.0 Hz), 3.80 (3H, s). C 16 H 14 O 3 254.0943 [M + H] + The HRMS m / z calculated for it, the measured value was 254.0935 [M + H] + 4-[(E)-2-(3-Methoxyphenyl)ethenyl]benzoic acid Anthony, Nahoum G, 2007, the above

[0230] 6-[(E)-2-(3-Methoxyphenyl)ethenyl]nicotinic acid This compound was prepared from its methyl ester and subsequently hydrolyzed.

[0231] Methyl 6-[(E)-2-(3-methoxyphenyl)ethenyl]nicotinate 3-Methoxybenzaldehyde (210 mg, 1.52 mmol), methyl 6-methylnicotinate (230 mg, 1.52 mmol), acetic anhydride (310 mg, 3.04 mmol) and a catalytic amount of zinc chloride were heated at 140 0 °C with stirring for 12 hours. Ethyl acetate and brine were added to the cooled reaction mixture, and the product was extracted. The organic layer was collected and dried (MgSO 4) Then, the solvent was removed under reduced pressure. The crude product was applied to a silica gel column, and the product was eluted with ethyl acetate / n-hexane 1:1. The fractions containing the required product were collected, and the solvent was removed under reduced pressure to obtain the desired substance as a yellow solid (87 mg, 21%), mp 170 - 173 o obtained as C. IR (cm -1 ). 1717, 1606, 1591, 1511, 1433, 1290, 1254, 1175, 1111, 1020, 844, 818, 760, 734 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 9.04 (1H, d, J = 2.0 Hz), 8.25 (1H, dd, J = 2.2 Hz, J = 8.2 Hz), 7.81 (1H, d, J = 16.0 Hz), 7.67 - 7.62 (3H, m), 7.28 (1H, d, J = 16.0 Hz), 7.00 (2H, d, J = 8.8 Hz), 3.88 (3H, s), 3.80 (3H, s). HRMS m / z C 16 H 16 O 3 N 270.1130 [M+H] + calculated for, found 270.1127 [M+H] +

[0232] 6 - [(E)-2-(3 - Methoxyphenyl)ethenyl]nicotinic acid Methyl 6 - [(E)-2-(3 - methoxyphenyl)ethenyl]nicotinate (80 mg, 0.297 mmol) was dissolved in methanol (5 mL), and an aqueous sodium hydroxide solution (145 mg) in water (10 mL) was added. The reaction mixture was heated under reflux for 3 hours. Methanol was removed under reduced pressure, and the remaining solution was cooled to 0 0 °C. Concentrated hydrochloric acid was added dropwise with vigorous stirring until pH 4. The yellow solid substance was collected by filtration, washed with water, and dried under reduced pressure at 50 °C to obtain the required substance (59 mg, 78%), melting point 230 - 233 °C (sublimes around 200 o °C). Infrared (cm -1) 1717, 1681, 1635, 1595, 1513, 1292, 1250, 1173, 1023, 825 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 9.03 (1H, d, J = 2.0Hz), 8.29 (1H, dd, J = 2.1Hz, J = 8.2Hz), 7.90 - 7.65 (4H, m), 7.29 (1H, d, J = 16.0Hz), 7.01 (2H, m), 3.80 (3H, s) HRMS m / z C 15 H 14 O 3 N 256.0974[M+H] + Calculated for, Found 256.0972[M+H] + (E)-Methyl 6-(4-fluoro-3-methoxystyryl)nicotinate 4-Fluoro-3-methoxybenzaldehyde (1.02 g, 6.62 mmol), methyl 6-methylnicotinate (1.00 g, 6.62 mmol) and zinc chloride (5 wt%) were dissolved in acetic anhydride (3 mL). The reaction mixture was heated at 140 o °C for 12 h with stirring. The reaction mixture was diluted with brine and ethyl acetate. A portion of the product did not dissolve in methanol or ethyl acetate (247 mg) and was filtered off. After extraction, the organic layer was collected, dried (MgSO 4 ) and the solvent was removed under reduced pressure to give a crude product, which was further purified by silica gel column chromatography using ethyl acetate / n-hexane (1 / 4), R F = 0.20. The product was obtained as white crystals (0.746 g, 39%), mp 150 - 153 o °C. IR (cm -1 ) 1711, 1638, 1590, 1515, 1458, 1436, 1418, 1343, 1275, 1157, 1124, 1114, 1031, 971, 850, 820 1H NMR (500 MHz, DMSO-d6) δ (ppm) 9.05 (1H, d, J = 2.0 Hz), 8.29 (1H, dd, J = 2.2 Hz & J = 8.2 Hz), 7.83 (1H, d, J = 16.1 Hz), 7.66 (1H, d, J = 7.8 Hz), 7.56 (1H, dd, J = 1.8 Hz & J = 7.0 Hz), 7.44 (1H, d, J = 16.1 Hz), 7.27 - 7.22 (2H, m), 3.91 (3H, s), 3.88 (3H, s). HRMS m / z C 16 H 15 O 3 NF 288.1036 [M + H] + Calculated for, Found 288.1039 [M + H] +

[0233] (E) 6-(4-Fluoro-3-methoxystyryl)nicotinic acid Methyl 6-[(E)-2-(4-fluoro-3-methoxyphenyl)ethenyl]nicotinate (0.500 g, 1.74 mmol) was suspended in methanol (5 mL), and sodium hydroxide solution (0.348 g, 8.71 mmol) was dissolved in water (20 mL). The reaction mixture was heated under reflux for 3 h. Methanol was removed under reduced pressure, and the water was cooled to 0 o °C. Concentrated hydrochloric acid was added dropwise with stirring at 0 o °C until the pH reached 4. The formed pale yellow solid was filtered, washed with water, and dried under reduced pressure to give the required product as a pale yellow solid (0.457 g, 96%) (mp > 230 o °C). IR (cm -1 ) 1718, 1621, 1598, 1514, 1268, 1160, 1120, 1028, 961, 854, 801 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 9.04 (1H, d, J = 2.0 Hz), 8.28 (1H, dd, J = 2.2 Hz & J = 8.2 Hz), 7.83 (1H, d, J = 16.1 Hz), 7.67 (1H, d, J = 8.2 Hz), 7.55 (1H, dd, J = 1.6 Hz & J = 7.4 Hz), 7.44 (1H, d, J = 16.1 Hz), 7.29 - 7.22 (2H, m). C 15 H 12 O 3 NF 273.08 [M] + Calculated LRMS M / z for, found 274.2 [M + H] + 。

[0234] (E)-Methyl 4-(2-(pyrimidin-5-yl)vinyl)benzoate 4-Methylpyrimidine (250 mg, 2.66 mmol) and methyl 4-formylbenzoate (436 mg, 2.66 mmol) were dissolved in acetic anhydride (1 mL), and zinc chloride (5 wt%) was added thereto. The reaction mixture was heated under reflux overnight. The black mass was triturated with ethyl acetate and filtered. The solid was washed with a small amount of methanol to give pale yellow microcrystals (236 mg, 37%), melting point > 230 o C was obtained. Infrared (cm -1 ) 1717, 1599, 1466, 1399, 1274, 1104, 1021, 965, 852, 778 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 9.16 (1H, s), 8.81 (1H, d, J = 5.2 Hz), 7.99 (2H, m), 7.88 (2H, d, J = 4.8 Hz), 7.67 (1H, d, J = 5.2 Hz), 7.48 (1H, d, J = 16.0 Hz), 3.87 (3H, s) C 14 H 13 O 2 N 2 241.0977 [M + H] + Calculated HRMS m / z for, found 241.0974 [M + H] +

[0235] (E)-4-(2-(Pyrimidin-5-yl)vinyl)benzoic acid Methyl 4-[(E)-2-(4-pyrimidinyl)ethenyl]benzoate (100 mg, 0.416 mmol) was suspended in methanol (2 mL), and an aqueous sodium hydroxide solution [NaOH (67 mg, 1.67 mmol) in water (10 mL)] was added. The reaction mixture was heated under reflux for 6 hours. The solvent was removed by evaporation to dryness, the white solid material was dissolved in water, and cooled to 0 o °C. Concentrated hydrochloric acid was added dropwise with stirring at 0 o °C until pH 4. The resulting “emulsion” was lyophilized to obtain the required product in quantitative yield (including sodium chloride) (mp > 230 o °C). Infrared (centi -1 ) 2498, 1687, 1585, 1281, 1172, 1007, 853, 780 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 13.00 (1H, br), 9.16 (1H, d, J = 0.8 Hz), 8.81 (1H, d, J = 5.2 Hz), 8.04 - 7.97 (3H, m), 7.85 (2H, d, J = 8.0 Hz), 7.67 (1H, dd, J = 5.2 Hz & J = 1.2 Hz), 7.46 (1H, d, J = 16.0 Hz). C 13 H 11 O 2 N 2 227.0821 [M + H] + Calculated HRMS m / z for, found 227.0822 [M + H] +

[0236] (E)-Methyl 4-(3-fluorostyryl)benzoate Diethyl 3-fluorobenzylphosphonate (1.35 g, 5.50 mmol) was dissolved in THF (10 mL, dry), and then 0 oCooled to C. Sodium hydride (300 mg, 60% suspension in oil, 7.50 mmol) was added portionwise with stirring. Methyl 4-formylbenzoate (0.903 g, 5.52 mmol) was dissolved in THF (10 mL, dry) and added with stirring at 0 o C. The reaction mixture was then stirred at room temperature for 1 h. 0 o C of water was added dropwise under nitrogen, and then dilute hydrochloric acid was added until pH 6. After extraction, the THF layer was separated, and the aqueous layer was extracted again with ethyl acetate. The combined organic layers were dried (MgSO4). TLC showed two spots: one corresponding to the product and the second spot corresponding to unreacted methyl 4-formylbenzoate. The solvent was removed under reduced pressure and then dissolved in DCM. Girard's reagent T (180 mg, 3.00 mmol) was dissolved in acetic acid (1.803 g, 30.00 mmol). The reaction mixture was stirred at room temperature for 2 h and then water was added. After extraction, the aqueous layer was extracted with DCM (2×25 mL). The combined organic layers were washed with brine (3×15 mL) and Na 2 CO 3 aqueous solution (3×15 mL), dried (MgSO 4 ), and evaporated under reduced pressure to give the required product as a white microcrystalline solid (0.490 g, 35%), mp 115 - 118 o C, R F = 0.80 (1 / 2 ethyl acetate / n-hexane). Infrared (cm -1 ) 1718, 1609, 1580, 1438, 1281, 1264, 1112, 960, 864, 792, 757, 700 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 7.98 (2H, d, J = 8.4 Hz), 7.76 (2H, d, J = 8.4 Hz), 7.54 - 7.41 (5H, m), 7.16 - 7.12 (1H, m), 3.86 (3H, s). C 16 H 13 O 2 F 256.0900 [M + H] + Calculated HRMS m / z for, found 256.0898 [M + H] +

[0237] (E)-4-(3-Fluorostyryl)benzoic acid Methyl 4-[(E)-2-(3-fluorophenyl)ethenyl]benzoate (0.480 g, 1.87 mmol) was suspended in methanol (5 mL), and sodium hydroxide solution (0.300 g, 7.50 mmol) was dissolved in water (15 mL). The reaction mixture was heated under reflux for 5 hours. Methanol was removed under reduced pressure, and the water content was cooled to 0 o °C. Concentrated hydrochloric acid was added dropwise with stirring at 0 o °C until the pH reached 4. The formed white crystalline substance was filtered, washed with water, and dried under reduced pressure to obtain the required product as white crystals (0.420 g, 93%) (melting point > 230 o °C). IR (cm -1 ) 3012, 1678, 1610, 1584, 1427, 1296, 1240, 1183, 1144, 950, 859, 774 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 7.66 (2H, d, J = 8.2 Hz), 7.32 (2H, d, J = 8.2 Hz), 7.26 - 7.18 (3H, m), 7.16 (1H, d, J = 16.4 Hz), 7.08 (1H, d, J = 16.4 Hz), 6.90 - 6.86 (1H, m). C 15 H 11 FO 2 Calculated LRMS M / z for C -

[0238] (E)-Methyl 6-(4-fluorostyryl)nicotinate 4-Fluorobenzaldehyde (0.821 g, 6.61 mmol), methyl 6-methylnicotinate (1.00 g, 6.61 mmol) and a catalytic amount of zinc chloride were dissolved in acetic anhydride (3 mL). The reaction solution was heated at 140 o °C for 12 hours with stirring. The reaction mixture was diluted with brine and ethyl acetate. After extraction, the organic layer was recovered and dried (MgSO 4) Then, the solvent was removed under reduced pressure to obtain a crude product, which was further purified by silica gel column chromatography using ethyl acetate / n-hexane (1 / 4), R F = 0.20. The product was obtained as white crystals (0.400 g, 24%), mp 142-144 o °C. IR (cm -1 ) 1716, 1588, 1509, 1435, 1287, 1225, 1193, 1114, 993, 847, 827, 773, 736 cm 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 9.07 (1H, d, J = 2.2 Hz), 8.29 (1H, dd, J = 8.2 Hz & J = 2.2 Hz), 7.87 (1H, d, J = 16.1 Hz), 7.81 - 7.77 (2H, m), 7.68 (1H, d, J = 8.2 Hz), 7.41 (1H, d, J = 16.1 Hz), 7.27 (2H, t, J = 8.8 Hz), 3.89 (3H, s) HRMS m / z C 15 H 13 O 2 NF 258.0930 [M+H] + calculated for, found 258.0933 [M+H] +

[0239] (E)-6-(4-Fluorostyryl)nicotinic acid Methyl 6-[(E)-2-(4-fluorophenyl)ethenyl]nicotinate (0.354 g, 1.38 mmol) was suspended in methanol (5 mL), and sodium hydroxide solution (0.374 g, 9.35 mmol) was dissolved in water (10 mL). The reaction mixture was heated under reflux for 3 hours. Methanol was removed under reduced pressure, and the water was cooled to 0 o °C. Concentrated hydrochloric acid was added dropwise with stirring at 0 o °C until the pH reached 4. The formed pale yellow substance was filtered, washed with water, and dried under reduced pressure to obtain the required product as a pale yellow solid (0.300 g, 98%) (melting point > 230 o °C). IR (cm -1) 2440, 1700, 1642, 1593, 1509, 1386, 1286, 1232, 1160, 965, 843, 822, 801, 731 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 13.32 (1H, br), 9.05 (1H, d, J = 1.9 Hz), 8.26 (1H, dd, J = 2.2 & J = 8.1 Hz), 7.85 (1H, d, J = 16.1 Hz), 7.80 - 7.77 (2H, m), 7.66 (1H, d, J = 7.8 Hz), 7.41 (1H, d, J = 16.1 Hz), 7.29 (2H, t, J = 8.9 Hz) HRMS m / z C 14 H 11 O 2 NF 244.0774 [M + H] + Calculated for, found 244.0773 [M + H] +

[0240] (E)-6-(3-(Trifluoromethyl)styryl)nicotinic acid Scott, Fraser Jet al, Bioorganic and Medicinal Chemistry Letters, 2016, vol. 26, # 15, p. 3478 - 3486

[0241] Synthesis of tail group dimers Synthesis of end group dimers containing alkylamidine or amidine with different end group lengths First, appropriate cyano dimers are prepared by reacting acid dimers with appropriate amino and cyano-functionalized alkanes using typical amide coupling conditions. The starting acid dimers are described in Lown; Krowicki, Journal of Organic Chemistry, 1985, vol. 50, # 20, p. 3774 - 3779. Next, the cyano dimers are converted to their corresponding imidate analogs via typical Pinner conditions, and then the resulting imidates are used without isolation to obtain the corresponding amidine dimers via reaction with appropriate amines. The ethyl imidate dimer is prepared according to Rao; Bathini; Lown, Journal of Organic Chemistry, 1990, vol. 55, # 2, p. 728 - 737. [Chemical formula] Scheme 2: Synthesis of alkylated amidine dimers or amidines with different tail group lengths

[0242] For the cyano dimer, the acid dimer (1 equivalent) was dissolved in DMF with HATU (1.2 equivalents) and tea (2.5 equivalents) and stirred at room temperature for 30 minutes. Appropriately, cyanoalkylamine (1 equivalent) was added thereto and stirred overnight. A saturated brine solution was added to the reaction mixture to form a precipitate. The precipitate was collected by filtration and air-dried, and was found to be the desired product. For the imidate dimer, an appropriate amount of cyano tail group dimer (0.5 - 1 mmol, 1 equivalent) was suspended in ethanol (20 mL, dry) and cooled to -60 o °C. Dry hydrogen chloride gas was generated from concentrated sulfuric acid and concentrated hydrochloric acid and bubbled into the solution until saturated (about 30 minutes to 1 hour). After warming the reaction mixture to room temperature, it was stirred at room temperature for 2 hours. The solvent was removed by evaporation under reduced pressure. The obtained solid was triturated in dry diethyl ether and collected by vacuum filtration. The presence of imidate was checked by NMR, and then the material was advanced immediately. For the unsubstituted amidine dimer, the imidate dimer was dissolved in ammonia in methanol (7M, 10 mL) and stirred at 55 o °C for 3 hours. The hot solution was filtered and the solid residue was washed with dilute hydrochloric acid. The solid was air-dried and found to be the product (yield about 80%). For the mono-substituted amidine dimer, the ethyl imidate dimer (0.30 - 0.65 mmol) was dissolved in ethanol to obtain a 0.5M solution, and then amine (2.0 equivalents) was added. The reaction mixture was stirred at 50 °C, followed by LCMS until completion (~2h). Then, the obtained solid was filtered, and Et 2Wash with O(10 mL). If the product does not crash, remove the solvent under vacuum and the resulting solid is Et 2 Wash with O(10 mL). For the disubstituted amidine dimer, ethyl imidate dimer (1.0 equiv) was dissolved in dry ethanol (0.1 M), and then amine (10 equiv) was added. The reaction mixture was stirred at 50 °C (or reflux) overnight (or until the reaction was complete), about 16 h. Then, the solid was filtered and washed with Et 2 Wash with O(10 mL). If the product is not crushed, remove the solvent under vacuum and the resulting solid is Et 2 Wash with O(10 mL). Trace amounts of unwanted mono- or disubstituted dimers were separated using HPLC purification. If shown and the mixture of mono- and disubstituted dimers could not be properly separated, the mixture was used without purification to form a complete mixture of S-MGB, which was separated by HPLC at that stage.

[0243] Details of the characterization of dimers containing alkyl amidines or amidines with different end group lengths

[0244] N-(2-Cyanoethyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Debart et al, Journal of Medicinal Chemistry, 1989, vol. 32, # 5, p. 1074 - 1083

[0245] N-(4-Cyanobutyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3128, 1635, 1498, 1305, 839 1H NMR (500 MHz, DMSO-d6) δ (ppm) 10.22 (s, 1H), 8.17 (d, J = 2.1 Hz, 1H), 8.09 (t, J = 5.8 Hz, 1H), 7.57 (d, J = 2.1 Hz, 1H), 7.20 (d, J = 2.0 Hz, 1H), 6.86 (d, J = 2.0 Hz, 1H), 3.95 (s, 3H), 3.81 (s, 3H), 3.19 (q, J = 7.1 Hz, 2H), 2.69 - 2.69 (m, 6H) 13 13C NMR (126 MHz, DMSO-d 6 ) δ (ppm) 128.2, 126.3, 117.9, 107.5, 103.9, 38.2, 37.4, 37.4, 35.9, 28.4, 22.4, 15.8 13C 17 1H 20 15N 6 16O 4 Calculated LRMS M / z for 372.39[M], found 373.2[M+H] +

[0246] N-(Cyanomethyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3338, 1762, 1390, 1207, 1114 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.28 (s, 1H), 8.71 (t, J = 5.6 Hz, 1H), 8.18 (d, J = 2.1 Hz, 1H), 7.58 (d, J = 2.1 Hz, 1H), 7.30 (d, J = 2.0 Hz, 1H), 6.95 (d, J = 2.0 Hz, 1H), 4.20 (d, J = 5.6 Hz, 2H), 3.95 (s, 3H), 3.85 (s, 3H) 13 13C NMR (126 MHz, DMSO-d 6) δ (ppm) 161.1, 156.9, 133.8, 128.2, 126.2, 121.7, 121.4, 119.3, 117.9, 107.6, 105.1, 37.4, 36.2, 27.1 C 14 H 14 N 6 O 4 Calculated LRMS M / z for 330.30[M], found 331.3[M+H] +

[0247] N-(5-Cyanopentyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3107, 1637, 1500, 1303, 769 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.26 - 10.22 (m, 1H), 8.17 (d, J = 2.1 Hz, 1H), 8.05 (t, J = 5.8 Hz, 1H), 7.59 (d, J = 2.3 Hz, 1H), 7.20 (d, J = 2.0 Hz, 1H), 6.85 (d, J = 2.0 Hz, 1H), 3.95 (s, 3H), 3.80 (s, 3H), 3.17 (q, J = 6.7 Hz, 2H), 2.49 - 2.46 (m, 2H), 1.58 (p, J = 7.2 Hz, 2H), 1.50 (p, J = 7.2 Hz, 2H), 1.42 - 1.33 (m, 2H) C 18 H 22 N 6 O 4 Calculated LRMS M / z for 386.41[M], found 387.2[M+H] +

[0248] N-(5-Amino-5-iminopentyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1) 3130, 1634, 1498, 1305, 840 1 1H NMR (500 MHz, acetone-d6) δ (ppm) 11.02 (s, 1H), 9.94 (s, 1H), 8.68 - 8.64 (m, 1H), 8.38 (d, J = 2.1 Hz, 1H), 7.98 - 7.94 (m, 1H), 7.82 (d, J = 2.1 Hz, 1H), 7.68 (d, J = 2.0 Hz, 1H), 7.34 (d, J = 2.0 Hz, 1H), 4.52 (s, 3H), 4.36 (s, 3H), 3.83 (q, J Hz, 2H) 13 13C NMR (126 MHz, DMSO-d6 6 ) δ (ppm) 170.9, 161.1, 156.9, 133.8, 128.2, 126.3, 123.2, 121.3, 118.0, 107.6, 104.1, 37.7, 37.4, 36.0, 31.5, 28.6, 24.0 C 17 H 23 N 7 O 4 LRMS M / z calculated for 389.42[M], found 390.2[M + H] +

[0249] N-(2-Amino-2-iminoethyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3115, 1643, 1442, 1309, 740 1 1H NMR (500 MHz, DMSO-d6 6 ) δ (ppm) 10.34 (s, 1H), 8.69 (s, 2H), 8.56 (t, J = 6.1 Hz, 1H), 8.18 (d, J = 2.1 Hz, 1H), 7.62 (d, J = 2.1 Hz, 1H), 7.30 (d, J = 2.0 Hz, 1H), 7.02 (d, J = 2.0 Hz, 1H), 4.09 (d, J = 5.3 Hz, 2H), 3.96 (s, 3H), 3.82 (s, 3H) 13 C NMR (126 MHz, DMSO-d 6 ) δ (ppm) 168.6, 161.8, 156.9, 133.8, 128.3, 126.2, 121.9, 121.7, 118.9, 107.7, 105.3, 37.5, 36.2 C 14 H 17 N 7 O 4 LRMS M / z calculated for 347.34[M], found 348.3[M+H] +

[0250] N-(6-Amino-6-iminohexyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.29 (s, 1H), 8.18 (d, J = 2.1 Hz, 1H), 8.06 (t, J = 5.8 Hz, 1H), 7.62 (d, J = 2.1 Hz, 1H), 7.20 (d, J = 2.0 Hz, 1H), 6.87 (d, J = 2.0 Hz, 1H), 3.95 (s, 3H), 3.80 (s, 3H), 3.17 (q, J = 6.9 Hz, 2H), 2.40 - 2.35 (m, 2H), 1.68 - 1.59 (m, 2H), 1.54 - 1.48 (m, 2H), 1.34 - 1.29 (m, 2H) C 18 H 25 N 7 O 4 LRMS M / z calculated for 403.44[M], found 404.3[M+H] +

[0251] N-(3-Imino-3-(methylamino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (cm -1) 3302, 3243, 3207, 3109, 1684, 1640, 1613, 1568, 1501, 1416, 1387, 1302, 1277, 1256, 1204, 1152, 1132, 1113, 1092, 1074, 885, 847, 812, 779, 748 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.26 (s, 1H), 8.26 (t, J = 5.75 Hz, 1H), 8.19 (d, J = 1.75 Hz, 1H), 7.58 (d, J = 1.75 Hz, 1H), 7.22 (d, J = 1.75 Hz, 1H), 6.91 (d, J = 1.75 Hz, 1H), 3.96 (s, 3H), 3.83 (s, 3H), 3.50 (m, 2H), 2.80 (s, 3H), 2.59 (t, J = 6.8 Hz, 2H) HRMS m / z calculated value, C 16 H 22 N 7 O 4 376.1728 [M+H] + , measured value 376.1734 [M+H] +

[0252] 1-Methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-N-(3-(methylamino)-3-(methylimino)propyl)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3452, 3300, 3254, 3213, 3123, 1663, 1632, 1566, 1545, 1535, 1499, 1435, 1395, 1306, 1289, 1256, 1213, 1194, 1148, 1119, 1092, 1026, 889, 856, 829, 812, 772, 748, 723 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.26 (s, 1H), 8.32 (t, J = 5.75 Hz, 1H), 8.19 (d, J = 1.75 Hz, 1H), 7.58 (d, J = 1.75 Hz, 1H), 7.22 (d, J = 1.75 Hz, 1H), 6.91 (d, J = 1.75 Hz, 1H), 3.96 (s, 3H), 3.83 (s, 3H), 3.46 (m, 2H), 3.02 (s, 3H), 2.77 (s, 3H), 2.71 (t, J = 6.8 Hz, 2H) HRMS m / z calculated value, C 17 H 24 N 7 O 4 390.1884 [M+H] + , measured value 390.1888 [M+H] +

[0253] N-(3-(Ethylamino)-3-iminopropyl)-1-methyl-4-(1-methyl-4-nitro group-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide IR (centi -1 ) 3051, 1494, 1247, 750 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.3 (s, 1H), 9.38 (s, 1H), 9.03 (s, 1H), 8.55 (s, 1H), 8.23 (t, J = 5.7 Hz, 1H), 8.18 (s, 1H), 7.57 (s, 1H), 7.21 (s, 1H), 6.91 (s, 1H), 3.95 (s, 3H), 3.82 (s, 3H), 3.50 (q, J = 6.1 Hz, 2H), 3.23 - 3.17 (m, 2H), 1.13 (t, J = 7.2 Hz, 3H) C 17 H 23 N 7 O 4 389.18 [M] + Calculated LRMS M / z for, measured value 390.3 [M+H] +

[0254] N-(3-Imino-3-(isopropylamino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3419, 1689, 1022, 999 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.3 (s, 1H), 9.26 (d, J = 7.9 Hz, 1H), 9.01 (s, 1H), 8.55 (s, 1H), 8.20 (t, J = 5.8 Hz, 1H), 8.18 (d, J = 1.3 Hz, 1H), 7.56 (d, J = 1.8 Hz, 1H), 7.21 (d, J = 1.3 Hz, 1H), 6.91 (d, J = 1.8 Hz, 1H), 3.95 (s, 3H), 3.82 (s, 3H), 3.79 - 3.73 (m, 1H), 3.50 (q, J = 6.1 Hz, 2H), 2.57 (t, J = 6.3 Hz, 2H), 1.14 (d, J = 6.4 Hz, 6H) C 18 H 25 N 7 O 4 403.20 [M] + Calculated LRMS M / z for, found 404.3 [M+H] +

[0255] (Z)N-(3-(Ethylamino)-3-(ethylimino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3263, 1629, 1305, 1118 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.2 (s, 1H), 9.26 - 9.20 (m, 1H), 8.59 - 8.53 (m, 1H), 8.28 (t, J = 5.8 Hz, 1H), 8.19 (d, J = 1.5 Hz, 1H), 7.56 (d, J = 1.9 Hz, 1H), 7.21 (d, J = 1.5 Hz, 1H), 6.92 (d, J = 1.9 Hz, 1H), 3.95 (s, 3H), 3.82 (s, 3H), 3.49 - 3.41 (m, 2H), 3.23 - 3.16 (m, 2H), 2.71 (t, J = 6.6 Hz, 2H), 1.18 (t, J = 7.3 Hz, 3H), 1.14 (t, J = 7.2 Hz, 3H) C 19 H 27 N 7 O 4 417.21[M] + Calculated LRMS M / z for [M], found 418.4 [M + H] +

[0256] N-(3-Imino-3-(methoxyamino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3315, 1641, 1494, 1257 1 H NMR (500 MHz、DMSO-d 6 ) δ (ppm) 10.2 (s、1H)、8.17 (s,1H)、7.97 (t、J = 5.4 Hz、1H)、7.59-7.56 (m、1H)、7.23-7.20 (m、1H)、6.84-6.82 (m、1H)、3.95 (s、3H)、3.81 (s、3H)、3.58 (s、3H)、3.37-3.33 (m、2H)、2.20 (t、J = 7.4 Hz、2H) C 16 H 21 N 7 O 5 391.16[M] + Calculated LRMS M / z for [M], found 392.3 [M + H] + N-(3-Imino-3-(nonylamino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide IR(cm -1)3263, 3251, 3238, 3213, 3169, 3142, 3142, 3116, 2922, 2852, 1658, 1639, 1593, 1550, 1500, 1469, 1442, 1423, 1409, 1379, 1319, 1284, 1257, 1224, 1199, 1170, 1128, 1074, 1066, 1024, 1012, 989, 920, 889, 866, 829, 815, 800, 786, 752, 738, 717, 696, 667, 628 1 H NMR (500 MHz, d 6 -DMSO) δ (ppm) 10.24 (1H, s), 9.32 (1H, bs), 9.02 (1H, s), 8.54 (1H, s), 8.20 - 8.18 (2H, m), 7.57 (1H, s), 7.18 (1H, s), 6.93 (1H, s), 3.95 (3H, s), 3.81 (3H, s), 3.51 - 3.48 (2H, m), 3.15 - 3.11 (2H, m), 2.59 (2H, t, J = 6.2 Hz), 1.51 - 1.45 (2H, m), 1.22 - 1.19 (12H, m), 0.83 - 0.80 (3H, m) C 24 H 37 N 7 O 4 487.6[M] + Calculated LRMS M / z for, found 488.4[M + H] +

[0257] (E)N-(3-(Butylamino)-3-(butylimino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide IR(cm -1)3269.34, 3226.91, 3217.27, 2962.4, 3111.18, 2960.73, 2908.65, 2973.94, 1570.06, 1527.62, 1436.97, 1419.61, 1386.82, 1307.74, 1257.59, 1170.79, 1134.14, 112.93, 1039.63, 1024.2, 1006.84, 985.62, 947.05, 935.48, 837.11, 812.03, 793, 75.38, 731, 738.74, 717.52, 705.95, 684.73, 667.37, 651.94, 638.44, 623.01 1 H NMR (500 MHz, d 6 -DMSO) δ 10.27 (1H, s), 9.30 (1H, t, J = 4.5 Hz), 8.64 (1H, t, J = 5.5 Hz), 8.31 (1H, t, J = 6 Hz), 8.17 (1H, s), 7.20 (1H, s), 6.93 (1H, s), 3.95 (3H, s), 3.82 (3H, s), 3.48 - 3.45 (2H, m), 3.40 - 3.36 (2H, m), 3.18 - 3.14 (2H, m), 2.73 (2H, t, J = 6.5 Hz), 1.57 - 1.47 (4H, m), 1.33 - 1.27 (4H, m), 0.89 - 0.85 (6H, m) C 23 H 35 N 7 O 4 473.28[M] + Calculated LRMS M / z for, found 474.0[M + H] +

[0258] N-(3-Imino-3-(pentylamino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared -1 3278.99, 3109.25, 2935.66, 1637.56, 1406.11, 1315.45, 1199.72, 1178.51, 1128.36, 717.52 1H NMR (500 MHz, d6-DMSO) δ 10.25 (1H, s), 9.38 (1H, s), 9.05 (1H, s), 8.58, (1H, s), 8.21 - 8.17 (2H, m), 7.56 (1H, s), 7.19 (1H, s), 6.92 (1H, s), 3.94 (3H, s), 3.81 (3H, s), 3.50 (2H, s), 3.15 (bs, 2H), 2.60 (2H, bs), 1.50 (2H, s), 1.25 (4H, s), 0.82 (3H, s) HRMS m / z calculated value, C20H30N7O4 432.2354 [M+H]+, measured value 432.2355 [M+H]+

[0259] (Z)-N-(3-(Heptylamino)-3-(heptylimino)propyl)-1-methyl-4-(1-methyl-4-nitro group-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3242.34, 3124.68, 2956.87, 2929.87, 2856.58, 1643.35, 1570.06, 1502.55, 1463.97, 1406.11, 1357.89, 1305.81, 1247.94, 1184.29, 1172.72, 1089.78, 1031.92, 773.46, 750.31, 721.38, 667.37, 650.01, 607.58 1 H NMR (500 MHz, d 6 -DMSO) δ 10.27 (1H, s), 9.28 (1H, s), 8.62 (1H, s), 8.29 (1H, s), 8.17 (1H, s), 7.56, (1H, s), 7.19 (1H, s), 6.94 (1H, s), 3.95 (3H, s), 3.82 (3H, s), 3.50 (2H, s), 3.15 (2H, s), 2.73 (2H, s), 1.54 - 1.50 (4H, m), 1.24 (18H, bs), 0.83 (6H, s) C 29 H 47 N 7 O 4 557.37 [M] +Calculated LRMS M / z for, measured value 558.4 [M+H] + Calculated HRMS m / z, C 29 H 48 N 7 O 4 558.3762 [M+H] + , measured value 558.3756 [M+H] +

[0260] N-(3-((3-(Dimethylamino)propyl)amino)-3-imino-propyl)-1-methyl-4-(1-methyl-4-nitro group-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3242, 1639, 1305, 750 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm): 10.3 (s, 1H), 8.24-8.20 (m, 1H), 8.19 (s, 1H), 7.58 (s, 1H), 7.20 (s, 1H), 6.94 (s, 1H), 3.95 (s, 3H), 3.82 (s, 3H), 3.55-3.47 (m, 2H), 3.21-3.16 (m, 2H), 2.84 -2.79 (m, 2H), 2.32-2.28 (m, 2H), 2.14 (s, 6H), 1.68-1.65 (m, 2H) C 20 H 30 N 8 O 4 446.51 [M] + Calculated LRMS M / z for, measured value 447.3 [M+H] + C 20 H 31 N 8 O 4 447.2463 [M+H] + Calculated HRMS m / z for, measured value 447.2462 [M+H] +

[0261] N-(3-Imino-3-thiomorpholinopropyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3271, 1641, 1307, 750 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.3 (s, 1H), 9.38 (s, 1H), 8.87 (s, 1H), 8.36 (t, J = 5.8 Hz, 1H), 8.18 (d, J = 2.0 Hz, 1H), 7.62 (d, J = 2.0 Hz, 1H), 7 / 24 (d, J = 2.0 Hz, 1H), 6.95 (d, J = 2.0 Hz, 1H), 3.97 - 3.92 (m, 5H), 3.88 - 3.82 (m, 5H), 3.45 (d, J = 6.3 Hz, 2H), 2.88 - 2.76 (m, 6H) C 19 H 25 N 7 O 4 S 447.17[M] + Calculated LRMS M / z for, found 448.2[M+H] + C 19 H 26 N 7 O 4 S 448.1761[M+H] + Calculated HRMS m / z for, found 448.1759[M+H] +

[0262] N-(3-Imino-3-morpholinopropyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3140, 1654, 1307, 1116 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.32 (s, 1H), 8.36 (s, 1H), 8.18 (s, 1H), 7.61 (s, 1H), 7.23 (s, 1H), 6.95 (s, 1H), 3.95, 3.83 (s, 3H), 3.71 - 3.69 (m, 4H), 3.49 - 3.43 (m, 2H), 2.97 - 2.95 (m, 4H), 2.85 - 2.79 (m, 2H) C 19 H 25 N 7 O 5 431.45[M] + Calculated LRMS M / z for, found 432.2[M + H] + C 19 H 25 N 7 O 5 432.1990[M + H] + Calculated HRMS m / z for, found 432.1987[M + H] +

[0263] N-(3-Imino-3-(piperidin-1-yl)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3082, 1639, 1305, 750 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.3 (s, 1H), 9.03 (s, 1H), 8.51 (s, 1H), 8.30 (s, 1H), 8.18 (d, J = 1.7 Hz, 1H), 7.58 (s, 1H), 7.21 (s, 1H), 6.93 (s, 1H), 3.95 (s, 3H), 3.82 (s, 3H), 3.67 - 3.63 (m, 2H), 3.54 - 3.49 (m, 2H), 3.47 - 3.40 (m, 2H), 3.03 - 2.98 (m, 1H), 2.80 - 2.71 (m, 2H), 1.68 - 1.52 (m, 7H) C 20 H 27 N 7 O 4 429.48[M]+ Calculated LRMS M / z for, measured value 430.3 [M+H] + C 20 H 28 N 7 O 4 430.2197 [M+H] + Calculated HRMS m / z for, measured value 430.2196 [M+H] +

[0264] N-(3-Imino-3-(4-methylpiperazin-1-yl)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3091, 1490, 1309, 798 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.31 (m, 1H), 9.27 (s, 1H), 8.36 - 8.31 (m, 1H), 8.20 - 8.18 (m, 1H), 7.60 (s, 1H), 7.23 (s, 1H), 6.94 (s, 1H), 3.95 (s, 3H), 3.83 (s, 3H), 3.70 - 3.66 (m, 2H), 3.60 - 3.54 (m, 2H), 3.06 - 2.99 (m, 8H), 2.20 (s, 3H) C 20 H 28 N 8 O 4 444.50 [M] + Calculated LRMS M / z for, measured value 445.3 [M+H] + C 20 H 29 N 8 O 4 445.2306 [M+H] + Calculated HRMS m / z for, measured value 445.2304 [M+H] +

[0265] N-(3-imino-3-((2-(tetrahydro-2H-pyran-4-yl)ethyl)amino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 2931, 1631, 1303, 748 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.3 (s, 1H), 9.38 (s, 1H), 9.08 (s, 1H), 8.58 (s, 1H), 8.23 (s, 1H), 8.19 (s, 1H), 7.59 (s, 1H), 7.20 (s, 1H), 6.97 (s, 1H), 3.96 (s, 3H), 3.83 (3H), 3.81 - 3.75 (m, 2H), 3.56 - 3.48 (m, 2H), 1.60 - 1.43 (m, 7H), 1.20 - 1.09 (m, 3H) C 22 H 31 N 7 O 5 473.53[M] + Calculated LRMS M / z for, found 474.3[M + H] + C 22 H 32 N 7 O 5 474.2459[M + H] + Calculated HRMS m / z for, found 474.2456[M + H] +

[0266] N-(5-((12-imino-2,5,8-trioxa-11-azatetradecan-14-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 2873, 1647, 1307, 1093 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.30 (s, 1H), 9.56 (s, 1H), 9.17 (s, 1H), 8.69 (s, 1H), 8.23 (t, J = 5.9 Hz, 1H), 8.19 - 8.17 (m, 1H), 7.61 - 7.59 (m, 1H), 7.23 - 7.21 (m, 1H), 6.95 - 6.93 (m, 1H), 3.95 (s, 3H), 3.82 (s, 3H), 3.48 - 3.36 (m, 14H), 3.22 (s, 3H), 2.66 - 2.62 (m, 2H) C 22 H 33 N 7 O 7 507.55[M] + Calculated LRMS M / z for, found 508.3[M + H] + C 22 H 33 N 7 O 7 508.2514[M + H] + Calculated HRMS m / z for, found 508.2500[M + H] +

[0267] N-(3-Imino-3-((2-(4-methylpiperazin-1-yl)ethyl)amino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 2939, 1641, 1305, 750 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.35 (s, 1H), 8.27 (t, J = 5.4 Hz, 1H), 8.19 - 8.17 (m, 1H), 7.65 - 7.62 (m, 1H), 7.24 - 7.22 (m, 1H), 6.98 - 6.95 (m, 1H), 3.95 (s, 3H), 3.82 (s, 3H), 3.54 - 3.49 (m, 2H), 3.31 (t, J = 6.2 Hz, 2H), 2.87 (t, J = 6.2 Hz, 2H), 2.28 - 2.17 (m, 8H), 2.13 - 2.05 (m, 5H) C22 H 33 N 9 O 4 487.57[M] + Calculated LRMS M / z for, measured value 488.1[M+H] + C 22 H 34 N 9 O 4 488.2728[M+H] + Calculated HRMS m / z for, measured value 488.2723[M+H] +

[0268] N-(3-Imino-3-(phenethylamino)propyl)-1-methyl-4-(1-methyl-4-nitro group-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 2964, 1307, 740, 694 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.40 (s, 1H), 9.78 (s, 1H), 9.29 (s, 1H), 8.84 (s, 1H), 8.32 (t, J = 5.7 Hz, 1H), 8.17 (d, J = 1.7 Hz, 1H), 7.66 (d, J = 1.7 Hz, 1H), 7.30 - 7.25 (m, 6H), 6.99 (d, J = 1.7 Hz, 1H), 3.94 (s, 3H), 3.82 (s, 3H), 3.54 - 3.50 (m, 2H), 3.48 - 3.43 (m, 2H), 2.88 - 2.83 (m, 2H), 2.67 (t, J = 6.4 Hz, 2H) C 23 H 27 N 7 O 4 465.51[M] + Calculated LRMS M / z for, measured value 466.3[M+H] + C 23 H 28 N 7 O 4 466.2197[M+H] +HRMS m / z calculated, found 466.2193 [M+H] +

[0269] N-(3-imino-3-((2-thiomorpholinoethyl)amino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2- Infrared (centi -1 ) 3120, 1635, 1305, 752 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.36 (s, 1H), 8.28 (t, J = 5.7 Hz, 1H), 8.18 - 8.16 (m, 1H), 7.64 - 7.62 (m, 1H), 7.23 - 7.21 (m, 1H), 6.99 - 6.97 (m, 1H), 3.95 (s, 3H), 3.82 (s, 3H), 2.62 - 2.59 (m, 8H), 2.56 - 2.52 (m, 8H) C 21 H 30 N 8 O 4 S 490.58 [M] + LRMS M / z calculated, found 491.3 [M+H] + C 21 H 31 N 8 O 4 S 491.2183 [M+H] + HRMS m / z calculated, found 491.2179 [M+H] +

[0270] N-(3-((2,2-difluoroethyl)amino)-3-iminopropyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide Proper separation of the mono- and di-substituted dimers could not be achieved, and thus the mixture was used without purification. 50:50 mixture of mono (m / z 426.2 [M+H] + ) and di-substituted (m / z 490.2 [M+H] +) It was an amidine.

[0271] (Z)-N-(3-((2,2-difluoroethyl)amino)-3-((2,2-difluoroethyl)imino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide Proper separation of the mono- and disubstituted dimers could not be achieved, and thus the mixture was used without purification. 50:50 of the mono (m / z 426.2 [M+H] + ) and the disubstituted (m / z 490.2 [M+H] + ) It was an amidine.

[0272] N-(3-imino-3-((2-methoxyethyl)amino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3132, 1637, 1494, 1309, 752 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.35 (s, 1H), 9.63 (s, 1H), 9.24 (s, 1H), 8.76 (s, 1H), 8.26 (t, J = 5.8 Hz, 1H), 8.18 (d, J = 2.0 Hz, 1H), 7.63 (d, J = 2.1 Hz, 1H), 7.23 (d, J = 1.8 Hz, 1H), 6.95 (d, J = 2.0 Hz, 1H), 3.95 (s, 3H), 3.82 (s, 3H), 3.54 - 3.49 (m, 2H), 3.47 (t, J = 5.3 Hz, 2H), 3.41 - 3.37 (m, 2H), 3.25 (s, 3H), 2.67 (t, J = 6.5Hz, 2H) C 18 H 25 N 7 O 5 LRMS M / z calculated for 419.44[M], found 420.3[M+H] +

[0273] (Z)N-(3-((2-Methoxyethyl)amino)-3-((2-methoxyethyl)imino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide 1 H NMR (500 MHz, CDCl 3 ) δ (ppm) 8.92 (s, 1H), 7.58 (d, J = 2.0 Hz, 1H), 7.49 (d, J = 2.0 Hz, 1H), 7.29 (d, J = 2.0 Hz, 1H), 6.78 (t, J = 6.0 Hz, 1H), 6.41 (d, J = 1.8 Hz, 1H), 6.23 (s, 1H), 4.03 (s, 3H), 3.87 (s, 3H), 3.61 (q, J = 6.0 Hz, 3H), 3.51 - 3.41 (m, 7H), 3.39 - 3.29 (m, 7H), 2.54 - 2.48 (m, 2H) C 21 H 31 N 7 O 6 Calculated LRMS M / z for 477.52[M], found 478.3[M+H] +

[0274] N-(5-((12-Imino-2,5,8-trioxa-11-azatetradecan-14-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 2873, 1647, 1307, 1093 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.30 (s, 1H), 9.56 (s, 1H), 9.17 (s, 1H), 8.69 (s, 1H), 8.23 (t, J = 5.9 Hz, 1H), 8.19 - 8.17 (m, 1H), 7.61 - 7.59 (m, 1H), 7.23 - 7.21 (m, 1H), 6.95 - 6.93 (m, 1H), 3.95 (s, 3H), 3.82 (s, 3H), 3.48 - 3.36 (m, 14H), 3.22 (s, 3H), 2.66 - 2.62 (m, 2H) C 22 H 33 N 7 O 7 Calculated LRMS M / z for 507.55[M], found 508.3[M + H] + C 22 H 33 N 7 O 7 508.2514[M + H] + Calculated HRMS m / z for, found 508.2500[M + H] +

[0275] Synthesis of Tail Group Dimers Containing NH Pyrrole The tail group dimers were prepared by amide coupling of the appropriate nitro pyrrole carboxylic acid (either NH or NMe) to the tail group monomer as needed.

Chemical Structure

[0276] For the case of the amidine-containing tail group monomer: Step1: Appropriately dissolve trichloroacetyl pyrrole (10.48 mmol) in DMF (15 mL), add dropwise 3-aminopropionitrile (1.5 mL, 20.97 mmol) in DMF (15 mL), and stir the reaction mixture at room temperature overnight. After completion, add saturated brine solution (50 mL), observe the precipitate, collect it by filtration, air-dry it, and find that it is the desired product (~90% yield). Procedure 2: The appropriate nitrile tail group monomer (3.60 mmol) was suspended in ethanol (50 mL, dry) and cooled to -60 o °C. Dry hydrogen chloride gas was generated from concentrated sulfuric acid and concentrated hydrochloric acid and bubbled into the solution until saturated (about 30 minutes to 1 hour). After warming the reaction mixture to room temperature, it was stirred at room temperature for 2 hours. The solvent was removed by evaporation under reduced pressure. The resulting solid was triturated in dry diethyl ether and recovered by vacuum filtration. The presence of ethyl imidate was checked by NMR and then the material was advanced immediately. Ethyl imidate was dissolved in ammonia in methanol (7 M, 10 mL) and stirred at 55 o °C for 3 hours. The hot solution was filtered and the solid residue was washed with dilute hydrochloric acid. The solid was air-dried and found to be the product (yield about 80%).

[0277] For the morpholine-containing tail group monomer: Appropriately, trichloroacetylpyrrole (1.16 mmol) was dissolved in DCM (10 mL), and 2-morpholinoethane-1-amine (151 mg, 153 μL, 1.16 mmol) was added thereto. The reaction was stirred at room temperature overnight. Then, to promote precipitation of the product, the reaction was cooled to 0 o °C. The product was isolated by Buchner filtration and air-dried (yield about 75%).

[0278] For the amidine or morpholine-containing tail group monomer (Steps (i) and (ii) of Scheme 3): The amidine / morpholine monomer (0.25 mmol) was dissolved in methanol (25 mL), cooled with ice water, and then Pd / C-10% (50 mg) was added portionwise with stirring under hydrogen. The reaction mixture was hydrogenated overnight at room temperature and atmospheric pressure. The catalyst was removed over celite, and the solvent was removed under reduced pressure. The amine thus formed was dissolved in DMF (1 mL, dry) and treated with a dropwise addition of the trichloroacetyl derivative of either the NH or NMe monomer (depending on the final anticipated version of the dimer) in DMF (2 - 3 mL). The reaction was stirred overnight, and the solvent was evaporated under reduced pressure to concentrate. The resulting mixture was diluted with a minimal amount of methanol, and diethyl ether was added dropwise until the product precipitated. This was filtered and air-dried to obtain the desired product (yield 20 - 50%).

[0279] N-(2-Cyanoethyl)-4-nitro-1H-pyrrole-2-carboxamide IR (cm -1 ) 3340, 3165, 3138, 3099, 1643, 1568, 1567, 1494, 1475, 1440, 1413, 1384, 1361, 1311, 1261, 1261, 1234, 1215, 1139, 1109, 1070, 1041, 1010, 9972, 950, 921, 877, 848, 835, 813, 804, 785, 752, 719, 700, 682, 6 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 12.28 (1H, s), 8.78 (1H, t, J = 5.2 Hz), 7.92 (1H, s), 7.45 (1H, s), 3.49 (2H, m), 2.75 (2H, t, J = 6.5 Hz) C 8 H 8 N 4 O 3 208.1[M] + Calculated LRMS M / z for, found 207.2[M-H] - .

[0280] N-(2-Cyanoethyl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide Prepared as described in Federico et al, Gazzetta Chimica Italiana, 97, 1110 - 15, 1967.

[0281] N-(3-Amino-3-iminopropyl)-4-nitro-1H-pyrrole-2-carboxamide Infrared -1 3215, 3099, 2158, 2029, 1685, 1639, 1535, 1492, 1469, 1415, 1352, 1311, 1253, 1226, 1205, 1143, 1107, 842, 783, 752, 705 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 12.78 (1H, s), 9.01 (2H, s), 8.74 (1H, s), 8.60 (2H, s), 7.92 - 7.91 (1H, m), 7.49 (1H, s), 3.58 - 3.54 (2H, m), 2.63 (2H, t, J = 6Hz) C 8 H 11 N 5 O 3 225.2 [M] + Calculated LRMS M / z for, found 226.1 [M + H] + .

[0282] N-(3-Amino-3-iminopropyl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide Prepared as described in Berta et al, Journal of Medicinal Chemistry, 2004, Vol. 47, No. 10.

[0283] N-(2-Morpholinoethyl)-4-nitro-1H-pyrrole-2-carboxamide Infrared (cm -1) 3402, 3215, 3142, 3101, 2970, 2862, 2810, 2783, 2160, 2032, 1629, 1618, 1575, 1533, 1500, 1475, 1438, 1355, 1319, 1280, 1261, 1226, 1209, 1139, 1112, 1066, 1026, 1026, 935, 916, 860, 842, 802, 771, 746, 613 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 12.69 (1H, s), 8.38 - 8.35 (1H, m), 7.88 (1H, s), 7.42 (1H, s), 3.57 - 3.55 (4H, m), 3.37 - 3.33 (2H, m), 2.45 - 2.40 (6H, m); C 11 H 16 N 4 O 4 268.1 [M] + Calculated LRMS M / z for, found 269.3 [M + H] + 。

[0284] 1-Methyl-N-(2-morpholinoethyl)-4-nitro-1H-pyrrole-2-carboxamide Prepared as described in Vooturi, Sunil K et al, Journal of Medicinal Chemistry, 2009, vol. 52, #16, p. 5020 - 5031.

[0285] N-(3-Amino-3-iminopropyl)-4-(4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared -1 3257, 3134, 3113, 3080, 3061, 2983, 2918, 2854, 1685, 1637, 1581, 1475, 1406, 1375, 1313, 1288, 1257, 1211, 1136, 1097, 1045, 964, 825, 810, 750, 636 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 12.80 (1H, s), 11.29 (1H, s), 10.24 (1H, s), 8.9 (2H, bs), 8.7 (2H, bs), 8.31 (1H, t, J = 6 Hz), 7.96 (1H, bs), 7.61 - 7.58 (1H, m), 7.19 (1H, bs), 6.90 - 6.88 (1H, m), 3.57 - 3.53 (2H, m), 2.64 - 2.60 (2H, m) C 13 H 15 N 7 O 4 333.31[M] + Calculated LRMS M / z for, found 334.2[M + H] + HRMS m / z C 13 H 16 N 7 O 4 334.1258[M + H] + Calculated for, found 334.1262[M + H] + .

[0286] N-(3-Amino-3-iminopropyl)-1-methyl-4-(4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide IR (cm -1 ) 3387, 3136, 2987, 2949, 1631, 1587, 1550, 1531, 1504, 1469, 1435, 1419, 1402, 1373, 1309, 1284, 1259, 1199, 1180, 1130, 1130, 1095, 1008, 964, 839, 812, 796, 771, 746, 721, 707, 684, 634 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 12.77 (1H, s), 10.23 (1H, s), 8.9 (2H, bs), 8.49 (2H, bs), 8.25 (1H, t, J = 6Hz), 7.98 - 7.95 (1H, m), 7.61 - 7.58 (1H, m), 7.23 (1H, s), 6.86 (1H, s), 3.83 (3H, s), 3.53 - 3.48 (2H, m), 2.62 - 2.58 (2H, m) C 14 H 17 N 7 O 4 347.13[M] + Calculated LRMS M / z for, measured value 348.5[M+H] + HRMS m / z C 14 H 18 N 7 O 4 348.1415[M+H] + Calculated, measured value 348.1419[M+H] + 。

[0287] N-(5-((3-Amino-3-iminopropyl)carbamoyl)-1H-pyrrol-3-yl)-1-methyl-4-nitro-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3138, 1639, 1633, 1591, 1575, 1550, 1535, 1506, 1469, 1438, 1419, 1402, 1377, 1311, 1286, 1259, 1199, 1180, 1134, 1097, 871, 839, 812, 798, 773, 746, 723, 709, 636, 603 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 11.26 (1H, s), 10.21 (1H, s), 8.91 (2H, bs), 8.49 (2H, bs), 8.26 (1H, t, J = 6Hz), 8.18 (1H, bs), 3.95 (3H, s), 3.56 - 3.51 (2H, m), 2.63 - 2.59 (2H, m) C 14 H 17 N 7 O 4 347.13[M] + Calculated LRMS M / z for, measured value 348.2[M+H] + 。

[0288] N-(2-Morpholinoethyl)-4-(4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide IR (cm -1 ) 3244, 2972, 2574, 1637, 1508, 1436, 1394, 1369, 1311, 1261, 1220, 1134, 1099, 979, 854, 812, 775, 752 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 12.89 (1H, s), 11.39 (1H, s), 10.26 (1H, s), 8.36 (1H, t, J = 5.5), 7.96 (1H, s), 7.60 (1H, s), 7.20 (1H, s), 6.92 (1H, s), 4.05 - 3.95 (2H, m), 3.71 - 3.62 (2H, m), 3.60 - 3.53 (4H, m), 3.29 - 3.27 (2H, m), 3.20 - 3.08 (2H, m) C 16 H 20 N 6 O 5 376.15 [M] + Calculated LRMS M / z for, found 377.2 [M + H] + .

[0289] 1-Methyl-N-(2-morpholinoethyl)-4-(4-nitro-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide Infrared -1 3392, 3186, 3128, 2868, 1629, 1577, 1570, 1533, 1492, 1413, 1390, 1375, 1305, 1267, 1251, 1205, 1105, 985, 908, 848, 813, 775, 750, 709, 653 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 12.78 (1H, s), 10.26 (1H, s), 8.30 (1H, t, J = 5.6 Hz), 7.97 (1H, bs), 7.60 (1H, s), 7.25 (1H, s), 6.90 (1H, s), 4.01 - 3.98 (2H, m), 3.84 (3H, s), 3.68 - 3.64 (2H, m), 3.56 - 3.52 (2H, m), 3.28 (2H, t, J = 5.9 Hz), 3.15 - 3.12 (2H, m) C 17 H 22 N 6 O 5 390.17 [M] + Calculated LRMS M / z for, measured value 391.2 [M + H] + HRMS m / z C 17 H 23 N 6 O 5 391.1724 [M + H] + Calculated for, measured value 391.1726 [M + H] + 。

[0290] 1 - Methyl - N-(5 - ((2 - morpholinoethyl)carbamoyl)-1H - pyrrol - 3 - yl)-4 - nitro - 1H - pyrrole - 2 - carboxamide Infrared -1 3350, 3232, 2804, 1664, 1631, 1595, 1544, 1512, 1489, 1334, 1307, 1109, 1068, 858, 821, 746, 713 1 H NMR (500 MHz, DMSO - d 6 ) δ (ppm) 11.21 (1H, s), 10.20 (1H, s), 8.17 (1H, s), 7.99 - 7.96 (1H, m), 7.56 (1H, s), 7.13 (1H, s), 6.88 (1H, s), 3.95 (3H, s), 3.58 - 3.56 (4H, m), 3.37 - 3.34 (2H, m), 2.44 - 2.40 (4H, m), 2.36 - 2.32 (2H, m) C 17 H 22 N 6 O5 390.17 [M] + Calculated LRMS M / z for, measured value 391.4 [M + H] + C 17 H 22 N 6 O 5 Na 413.1544 [M + Na] + Calculated HRMS m / z for, measured value 413.1545 [M + H] + 。

[0291] Synthesis of quaternary ammonium tail group dimers Quaternary ammonium tail group oligomers can be prepared directly from their corresponding tertiary amine tail group oligomers by reacting them appropriately with alkyl halides.

[0292]

Chemical formula

[0293] In the production of the compounds of the present invention, N-ethyl-N,N-dimethyl-3-(1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide)propan-1-aminium bromide, N-(3-(dimethylamino)propyl)-1-methyl-4-(1-methyl-4-nitro-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide was reacted with 10 equivalents of bromoethane in acetonitrile (3 mL) at 80 o C for 20 hours to obtain a specific quaternary ammonium tail group oligomer, N-ethyl. The solid that precipitates as the volume of the reaction mixture decreases is the desired material.

[0294] N-ethyl-N,N-dimethyl-3-(1-methyl-4-(1-methyl-4-nitro group-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide)propan-1-aminium bromide Infrared cm -13495.01, 3325.28, 3240.41, 3113.11, 2358.94, 2160.27, 1978.97, 1647.21, 1595.13, 1570.06, 1533.41, 1516.05, 1436.97, 1421.54, 1402.25, 1363.67, 1311.59, 1259.52, 1213.23, 1203.58, 1118.71, 1118.71 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.31 (s, 1H), 8.22 (t, J = 5.9 Hz, 1H), 8.19 (d, J = 2.0 Hz, 1H), 7.63 (d, J = 2.0 Hz, 1H), 7.22 (d, J = 1.9 Hz, 1H), 6.94 (d, J = 1.9 Hz, 1H), 3.96 (s, 3H), 3.83 (s, 3H), 3.35 (q, J = 7.2 Hz, 3H), 3.32 - 3.23 (m, 4H), 3.01 (s, 6H), 1.91 (p, J = 6.5 Hz, 2H), 1.24 (t, J = 7.3 Hz, 3H). 13 C NMR (126 MHz, DMSO) δ (ppm) 161.87, 157.40, 134.27, 128.71, 126.76, 123.39, 121.92, 118.75, 108.15, 104.84, 61.09, 59.02, 50.05, 40.62, 37.95, 36.56, 36.08, 23.19, 8.26. C19H29N6O4+ 405.22 [M] + Calculated LCMS M / z for + .

[0295] Synthesis of the Compounds of the Invention Synthesis of Compounds Containing Alkylamidine or Amidine with Different Terminal Group Lengths

Chemical Structure

[0296] The nitro tail group dimer (or a mixture of mono- and disubstituted dimers) (0.3 mmol) was dissolved in methanol (25 mL), and 10% palladium on carbon (10 wt%) was added thereto with stirring at 0 o °C. The reaction mixture was hydrogenated at room temperature and atmospheric pressure for at least 5 hours, and complete reduction was monitored by LC-MS. It was removed on celite and concentrated under reduced pressure at 50 o °C. to obtain the amine tail group dimer, which was used in the next step without purification. The carboxylic acid head group dimer (1 eq) was dissolved in DMF (0.5 mL, dry), and HATU (2 eq) and DIPEA (1 eq) were added thereto, followed by stirring for 30 minutes to form the activated ester. The amine formed in the previous step was dissolved in DMF* (0.5 mL, dry) and slowly added to the activated ester at 0 o °C. Stirring was continued overnight at room temperature. The product was purified by HPLC, and the fractions containing the required substance were combined and lyophilized to obtain the desired product. *For the dimer obtained by HPLC purification and thus being the di-TFA salt, an additional 2 eq of DIPEA was added to this DMF solution.

[0297] Characterization Details of the compounds of the invention containing alkylamidines or amidines with different tail group lengths.

[0298] Ia1 (E)-6-(4-(dimethylamino)styryl)-N-(5-((5-((3-(ethylamino)-3-iminopropyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)nicotinamide Infrared (cm -1 ) 3273, 3041, 2951, 2870, 1654, 1570, 1294, 1244, 1201, 1174, 1130, 1109, 1014, 831, 698, 638 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) δ 10.43 (1H, s), 9.95 (1H, s), 9.34 (2H, s), 9.01 (2H, d, J = 17.2 Hz), 8.52 (1H, s), 8.23 (2H, d, J = 8.05 Hz), 8.17 (1H, t, J = 5.5 Hz), 7.70 (1H, d, J = 15.85 Hz), 7.61 - 7.60 (1H, d, J = 8.65 Hz), 7.53 (2H, d, J = 8.5 Hz), 7.33 (1H, s), 7.18 (1H, s), 7.13 - 7.10 (2H, m), 6.95 (1H, s), 6.75 (2H, d, J = 8.6 Hz), 3.87 (3H, s, under water peak), 3.18 (3H, s, under water peak), 3.55 - 3.40 (2H, m), 3.21 - 3.17 (2H, m), 2.97 (6H, s), 2.60 - 2.57 (2H, m), 1.10 - 1.20 (3H, m) C 33 H 39 N 9 O 3 609.3 [M] + Calculated LRMS M / z for, measured value 610.4 [M + H] + HRMS m / z C 33 H 40 O 9 N 3 610.3249 [M + H] + , Calculated value 610.3245 [M + H] for + .

[0299] Ia2(E)-N-(3-Imino-3-(methylamino)propyl)-1-methyl-4-(1-methyl-4-(4-(4-(trifluoromethyl)styryl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide IR (cm -1 ) 3310, 3201, 3003, 1638, 1580, 1526, 1464, 1435, 1404, 1323, 1265, 1199, 1165, 1109, 1065, 1015, 964, 949, 843, 799, 777, 758, 720 11H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.35 (s, 1H), 9.96 (s, 1H), 9.42 (m, 1H), 9.06 (s, 1H), 8.52 (s, 1H), 8.26 (t, J = 5.60 Hz, 4H), 7.99 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.15 Hz, 2H), 7.76 - 7.81 (m, 4H), 7.52 (s, 2H), 7.34 (d, J = 1.75 Hz, 1H), 7.19 (d, J = 1.75 Hz, 1H), 7.12 (d, J = 1.75 Hz, 1H), 6.91 (d, J = 1.75 Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.50 (m, 2H), 2.80 (d, J = 4.9 Hz, 3H), 2.56 (t, J = 6.45 Hz, 2H) HRMS m / z C 32 H 33 N 7 O 3 F 3 620.2591 [M+H] + Calculated for, found 620.2579 [M+H] + .

[0300] Ia3(E)-4-(4-(2-(Benz[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((3-imino-3-(methylamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide Infrared -1 3309, 3003, 2990, 1626, 1537, 1503, 1468, 1435, 1408, 1289, 1265, 1199, 1179, 1125, 1007, 957, 878, 849, 829, 800, 754, 720 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.38 (s, 1H), 9.96 (s, 1H), 9.41 (m, 1H), 9.06 (s, 1H), 8.52 (s, 1H), 8.21 (t, J = 5.60 Hz, 4H), 8.11 (s, 3H), 8.02 (d, J = 8.4 Hz, 2H), 7.82 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 16.5 Hz, 1H), 7.62 (d, J = 16.5 Hz, 1H), 7.34 (d, J = 1.75 Hz, 1H), 7.19 (d, J = 1.75 Hz, 1H), 7.13 (d, J = 1.75 Hz, 1H), 6.95 (d, J = 1.75 Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.50 (m, 2H), 2.80 (d, J = 4.9 Hz, 3H), 2.59 (t, J = 6.45 Hz, 2H) HRMS m / z C 31 H 32 N 9 O 4 594.2572 [M+H] + Calculated for, found 594.2570 [M+H] + .

[0301] Ia4(E)-N-(3-Imino-3-(methylamino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(naphthalen-2-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide IR -1 3296, 3103, 1670, 1638, 1580, 1533, 1464, 1435, 1404, 1267, 1199, 1182, 1130, 1063, 1011, 959, 895, 833, 801, 772, 745, 721 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.34 (s, 1H), 9.96 (s, 1H), 9.41 (m, 1H), 9.06 (s, 1H), 8.52 (s, 1H), 8.21 (t, J = 5.60 Hz, 1H), 8.08 (s, 1H), 8.01 (d, J = 8.4 Hz, 2H), 7.90 - 7.99 (m, 4H), 7.80 (d, J = 8.4 Hz, 2H), 7.45 - 7.51 (m, 4H), 7.35 (d, J = 1.75 Hz, 1H), 7.20 (d, J = 1.75 Hz, 1H), 7.13 (d, J = 1.75 Hz, 1H), 6.95 (d, J = 1.75 Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.50 (m, 2H), 2.80 (d, J = 4.9 Hz, 3H), 2.60 (t, J = 6.45 Hz, 2H) HRMS m / z C 35 H 36 N 7 O 3 602.2874 [M+H] + Calculated for, found 602.2866 [M+H] + .

[0302] Ia5 1-Methyl-4-(1-methyl-4-(4-((E)-4-(trifluoromethyl)styryl)benzamide)-1H-pyrrole-2-carboxamide)-N-((Z)-3-(methylamino)-3-(methylimino)propyl)-1H-pyrrole-2-carboxamide IR (cm -1 ) 3269, 3115, 2961, 1643, 1634, 1634, 1520, 1504, 1435, 1404, 1385, 1325, 1265, 1200, 1169, 1111, 1067, 1015, 968, 951, 845, 833, 818, 799, 773, 758, 719, 692, 675, 667, 627, 608 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.36 (s, 1H), 9.97 (s, 1H), 9.34 (m, 1H), 8.60 (m, 1H), 8.27 (t, J = 5.60 Hz, 4H), 7.99 (d, J = 8.4 Hz, 2H), 7.87 (d, J = 8.15 Hz, 2H), 7.76 - 7.81 (m, 4H), 7.52 (s, 2H), 7.34 (d, J = 1.75 Hz, 1H), 7.20 (d, J = 1.75 Hz, 1H), 7.12 (d, J = 1.75 Hz, 1H), 6.95 (d, J = 1.75 Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.47 (m, 2H), 3.03 (d, J = 4.75 Hz, 3H), 2.79 (d, J = 4.9 Hz, 3H), 2.72 (t, J = 6.45 Hz, 2H) HRMS m / z C 32 H 33 N 7 O 3 F 3 620.2591 [M+H] + Calculated for, found 620.2579 [M+H] + .

[0303] Ia6 4-(4-((E)-2-(Benz[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-1-methyl-N-(1-methyl-5-((Z)-3-(methylamino)-3-(methylimino)propyl)carbamoyl)-1H-pyrrol-3-yl)-1H-pyrrole-2-carboxamide Infrared -1 3309, 3003, 2990, 1626, 1537, 1503, 1468, 1435, 1408, 1289, 1265, 1199, 1179, 1125, 1007, 957, 878, 849, 829, 800, 754, 720 1 H NMR (500 MHz、DMSO-d 6 ) δ (ppm) 10.38 (s、1H)、9.97 (s、1H)、9.35 (m、1H)、8.60 (m、1H)、8.27 (t、J = 5.60 Hz、4H)、8.11 (s、3H)、8.02 (d、J = 8.4 Hz、2H)、7.82 (d、J = 8.4 Hz、2H)、7.70 (d、J = 16.5 Hz、1H)、7.62 (d、J = 16.5 Hz、1H)、7.34 (d、J = 1.75 Hz、1H)、7.20 (d、J = 1.75 Hz、1H)、7.13 (d、J = 1.75 Hz、1H)、6.95 (d、J = 1.75 Hz 、1H)、3.89 (s、3H)、3.83 (s、3H)、3.47 (m、2H)、3.03 (d、J = 4.6 Hz、3H)、2.79 (d、J = 4.9 Hz、3H)、2.72 (t、J = 6.45 Hz、2H) HRMS m / z C 31 H 32 N 9 O 4 594.2572 [M+H] +Calculated and measured value for it is 594.2570 [M+H] + .

[0304] Ia7 1-Methyl-4-(1-methyl-4-(4-((E)-2-(naphthalen-2-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-N-((Z)-3-(methylamino)-3-(methylimino)propyl)-1H-pyrrole-2-carboxamide IR (cm -1 ) 3279, 3127, 2955, 1653, 1578, 1522, 1437, 1404, 1364, 1265, 1200, 1179, 1126, 1015, 962, 897, 860, 818, 773, 745, 719 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.34 (s, 1H), 9.97 (s, 1H), 9.34 (m, 1H), 8.60 (m, 1H), 8.27 (t, J = 5.60 Hz, 1H), 8.08 (s, 1H), 8.00 (d, J = 8.4 Hz, 2H), 7.90 - 7.99 (m, 4H), 7.80 (d, J = 8.4 Hz, 2H), 7.45 - 7.51 (m, 4H), 7.35 (d, J = 1.75 Hz, 1H), 7.20 (d, J = 1.75 Hz, 1H), 7.13 (d, J = 1.75 Hz, 1H), 6.95 (d, J = 1.75 Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.48 (m, 2H), 3.03 (d, J = 4.6 Hz, 3H), 2.79 (d, J = 4.9 Hz, 3H), 2.72 (t, J = 6.45 Hz, 2H) HRMS m / z C 35 H 36 N 7 O 3 602.2874 [M+H] + Calculated and measured value for it is 602.2866 [M+H] + .

[0305] Ia8 6-((E)-4-(Dimethylamino)styryl)-N-(1-methyl-5-((1-methyl-5-(((E)-3-(methylamino)-3-(methylimino)propyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)nicotinamide Infrared (centi -1 ) 3045, 1571, 1166, 702 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.5 (s, 1H), 9.97 (s, 1H), 9.39 - 9.33 (m, 1H), 9.06 - 9.03 (m, 1H), 8.65 - 8.59 (m, 1H), 8.35 - 8.30 (m, 1H), 8.28 (t, J = 5.9 Hz, 1H), 7.78 - 7.69 (m, 2H), 7.55 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 1.5 Hz, 1H), 7.20 (d, J = 1.7 Hz, 1H), 7.17 - 7.10 (m, 2H), 6.94 (d, J = 1.7 Hz, 1H), 6.78 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.82 (s, 3H), 3.50 - 3.44 (m, 2H), 3.04 - 3.02 (m, 3H), 2.99 (s, 6H), 2.78 (d, J = 4.9 Hz, 3H), 2.74 - 2.69 (m, 2H) C 33 H 39 N 9 O 3 609.74[M] + Calculated LRMS M / z for, found 610.4[M + H] + HRMS m / z C 33 H 40 N 9 O 3 610.3249[M + H] + Calculated, found 610.3243[M + H] + .

[0306] Ia9(E)-6-(4-(Dimethylamino)styryl)-N-(5-((5-((3-imino-3-(methylamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)nicotinamide Infrared (centi -1 ) 3363, 1653, 1124, 954 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.5 (s, 1H), 9.97 (s, 1H), 9.46 - 9.40 (m, 1H), 9.08 - 9.04 (m, 2H), 8.53 (s, 1H), 8.33 (dd, J = 8.3, 2.2 Hz, 1H), 8.21 (t, J = 5.8 Hz, 1H), 7.79 - 7.72 (m, 2H), 7.55 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 1.5 Hz, 1H), 7.20 (d, J = 1.5 Hz, 1H), 7.16 - 7.09 (m, 2H), 6.94 (d, J = 1.5 Hz, 1H), 6.78 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.82 (s, 3H), 3.52 - 3.47 (m, 2H), 2.99 (6H), 2.80 (d, J = 4.9 Hz, 3H), 2.61 - 2.56 (m, 2H) C 32 H 37 O 3 N 9 595.71[M] + Calculated LRMS M / z for, found 596.4[M + H] + HRMS m / z C 32 H 38 O 3 N 9 596.3092[M + H] + Calculated, found 596.3084[M + H] + .

[0307] Ia10 1-Methyl-4-(1-methyl-4-(4-((E)-2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-N-((Z)-3-(methylamino)-3-(methylimino)propyl)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3300, 1633, 1172, 1128 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.97 (s, 1H), 9.37 - 9.32 (m, 1H), 9.29 (s, 1H), 8.60 (s, 1H), 8.27 (t, J = 5.9 Hz, 1H), 8.06 - 8.00 (m, 4H), 7.82 (d, J = 8.5 Hz, 2H), 7.80 - 7.76 (m, 1H), 7.71 - 7.62 (m, 3H), 7.34 (d, J = 1.6 Hz, 1H), 7.20 (d, J = 1.6 Hz, 1H), 7.12 (d, J = 1.6 Hz, 1H), 6.95 (d, J = 1.6 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.47 (q, J = 6.3 Hz, 2H), 3.03 (d, J = 4.7 Hz, 3H), 2.78 (d, J = 4.9 Hz, 2H), 2.72 (t, J = 6.5 Hz, 2H) C 35 H 36 N 8 O 3 616.73[M] + Calculated LRMS M / z for, found 617.4[M+H] + HRMS m / z C 35 H 37 N 8 O 3 617.2983[M+H] + Calculated for, found 617.2979[M+H] + .

[0308] Ia11 4-(4-((E)-2-(Benzothiazol-2-yl)vinyl)benzamide)-1-methyl-N-(1-methyl-5-(((Z)-3-(methylamino)-3-(methylimino)propyl)carbamoyl)-1H-pyrrol-3-yl)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3215, 1640, 1184, 1124, 721 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.38 - 9.33 (m, 1H), 8.63 - 8.59 (m, 1H), 8.31 - 8.26 (m, 1H), 8.14 (d, J = 8.1 Hz, 1H), 8.04 - 8.00 (m, 3H), 7.97 - 7.93 (m, 2H), 7.79 - 7.76 (m, 2H), 7.58 - 7.54 (m, 1H), 7.50 - 7.46 (m, 1H), 7.37 - 7.35 (m, 1H), 7.22 - 7.20 (m, 1H), 7.15 - 7.13 (m, 1H), 6.97 - 6.95(m, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.49 - 3.47 (m, 2H), 3.04 (d, J = 4.7 Hz, 3H), 2.79 (d, J = 4.7 Hz, 3H), 2.72 (t, J = 6.6 Hz, 2H). C 33 H 34 N 8 O 3 S 622.25[M] + Calculated LRMS M / z for, found 623.0[M + H] + HRMS M / z C 33 H 34 N 8 O 3 S 622.2575[M] + Calculated for, 623.2547[M + H] + was obtained.

[0309] Ia12N-((Z)-3-amino-3-(ethylimino)propyl)-4-(4-(4-((E)-2-(benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-1-methyl-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3084, 1610, 1261, 621 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4, (s, 1H), 9.97 (s, 1H), 9.40 (s, 1H), 9.05 (s, 1H), 8.56 (s, 1H), 8.22 - 8.18 (m, 1H), 8.12 (s, 3H), 8.03 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 16 Hz, 1H), 7.62 (d, J = 16 Hz, 1H), 7.36 (d, J = 1.7 Hz, 1H), 7.20 (d, J = 1.7 Hz, 1H), 7.13 (d, J = 1.7 Hz, 1H), 6.97 (s, J = 1.7 Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.54 - 3.49 (m, 2H), 3.25 - 3.18 (m, 2H), 2.60 (t, J = 6.2 Hz, 2H), 1.15 (t, J = 7.2 Hz, 3H) C 32 H 33 N 9 O 4 607.27[M] + Calculated LRMS M / z for, found 608.5 [M+H] + HRMS m / z C 32 H 34 O 4 N 9 608.2728 [M+H] + Calculated for, found 608.2722 [M+H] + .

[0310] Ia13 N-((Z)-3-Amino-3-(isopropylimino)propyl)-4-(4-(4-((E)-2-(benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-1-methyl-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3080, 1627, 1199, 800 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.37 (s, 1H, NH), 9.96 (s, 1H, NH), 9.22 (d, J = 8.55, 1H, NH), 8.97 (s, 1H, NH), 8.52 (s, 1H, NH), 8.16 - 8.12 (m, 1H, NH), 8.11 (m, 3H, ArH), 8.01 (d, J = 8.39 Hz, 2H, ArH), 7.82 (d, J = 8.39 Hz, 2H, ArH), 7.70 (d, J = 16.60, 1H, ArCH=CHR), 7.61 (d, J = 16.60, 1H, ArCH=CHR), 7.34 (d, J = 1.67 Hz, 1H, pyrroleH), 7.18 (d, J = 1.67Hz, 1H, pyrroleH), 7.11(d, J = 1.67Hz, 1H, pyrroleH), 6.97(d, J = 1.67Hz, 1H, pyrroleH), 3.88(s, 3H, pyrroleCH 3 ), 3.82(s, 3H, pyrroleCH 3 ), 3.79 ~ 3.72(m, 1H, RCH(CH 3 )) 2 ), 3.53 ~ 3.48(m, 2H, RNHCH 2 CH 2 R), 2.59 ~ 2.54(m, 2H, RNHCH 2 CH 2 R), 1.16(d, J = 6.41Hz, 6H, RCH(CH 3 )) 2 ) C 33 H 35 N 9 O 4 621.70[M] +Calculated LRMS M / z for, measured value 622.0 [M+H] + .

[0311] Ia14N-((Z)-3-Amino-3-(ethylimino)propyl)-1-methyl-4-(1-methyl-4-(4-((E)-2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide IR (cm -1 ) 3265, 3096, 1670, 1630, 1528, 1506, 1466, 1437, 1404, 1265, 1198, 1180, 1130, 1063, 862, 831, 799, 772, 750, 719, 685, 660, 625, 610 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.96 (s, 1H), 9.35 (s, 1H), 9.27 (s, 1H), 9.00 (s, 1H), 8.56 (s, 1H), 8.52 (s, 1H), 8.18 (t, J = 6.0 Hz, 1H), 8.05 - 7.99 (m, 5H), 7.84 - 7.80 (m, 2H), 7.79 - 7.74 (m, 2H), 7.68 - 7.63 (m, 3H), 7.34 (d, J = 1.7 Hz, 1H), 7.19 (d, J = 1.7 Hz, 1H), 7.12 (d, J = 1.7 Hz, 1H), 6.96 (d, J = 1.7 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.52 - 3.48 (m, 2H), 3.23 - 3.17 (m, 2H), 2.59(t, J = 6.5 Hz, 2H), 1.14 (t, J = 7.3 Hz, 3H). C 35 H 36 N 8 O 3 616.29 [M] + Calculated LRMS M / z for, measured value 617.1 [M+H] + HRMS m / z C 35 H 37 O 3 N 8617.2983 [M+H] + Calculated and measured value for 617.2978 [M+H] + .

[0312] Ia15(E)-N-(5-((5-((3-Imino-3-(isopropylamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-6-(4-methoxystyryl)nicotinamide Infrared (centi -1 ) 3394, 2941, 1341, 1022 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.5 (s, 1H), 9.96 (s, 1H), 9.26 - 9.21 (m, 1H), 9.08 - 9.06 (m, 1H), 8.98 (s, 1H), 8.53 (s, 1H), 8.26 (dd, J = 8.2, 2.3 Hz, 1H), 8.18 - 8.12 (m, 1H), 7.76 (d, J = 16 Hz, 1H), 7.69 - 7.63 (m, 3H), 7.35 (d, J = 1.7 Hz, 1H), 7.25 (d, J = 16 Hz, 1H), 7.18 (d, J = 1.7 Hz, 1H), 7.10 (d, J = 1.8 Hz, 1H), 7.00 (d, J = 8.9 Hz, 2H), 6.96 (d, J = 1.8 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.81 (s, 3H), 3.77 - 3.75 (m, 1H), 3.52 - 3.49 (m, 2H), 2.59 - 2.55 (m, 2H), 1.15 (d, J = 6.4 Hz, 6H) C 33 H 38 N 8 O 4 610.30 [M] + Calculated LRMS M / z for, measured value 611.4 [M+H] + .

[0313] Ia16(E)-4-(4-(4-Cyanostyryl)benzamide)-N-(5-((3-(ethylamino)-3-iminopropyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3128, 1631, 1195, 704 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.35 (s, 1H, NH), 9.50 (s, 1H, NH), 9.35 (s, 1H, NH), 9.00 (s, 1H, NH), 8.52 (s, 1H, NH), 8.18 (t, J = 5.52 Hz, 1H, NH), 8.01 - 7.97 (m, 2H, ArH), 7.89 - 7.82 (m, 4H, ArH), 7.81 - 7.77 (m, 2H, ArH), 7.56 (d, J = 16.5 Hz, 1H, ArCH=CHAr), 7.49 (d, J = 16.5 Hz, 1H, ArCH=CHAr), 7.33 (d, J = 1.67 Hz, 1H, pyrroleH), 7.18 (d, J = 1.67Hz, 1H, pyrroleH), 7.11(d, J = 1.67Hz, 1H, pyrroleH), 6.95(d, J = 1.67Hz, pyrroleH), 3.88(s, 3H, NCH 3 )), 3.82(s, 3H, NCH 3 ), 3.52~3.48(m, 2H, NHCH 2 ), 3.23~3.16(m, 2H, CH 3 CH 2 NH), 2.61~2.56(m, 2H, NHCH 2 CH 2 NH), 1.16~1.12(t, J = 7.24Hz, 3H, CH 3 CH 2 NH) LRMS M / z calculated value, measured value C 33 H 34 N 8 O 3 590.69[M] + , measured value 591.0[M+H] + HRMS m / z C 33H 35 O 3 N 8 591.2827 [M+H] + Calculated and measured value for it is 591.2819 [M+H] + 。

[0314] Ia17(E)-4-(4-(4-Cyanostyryl)benzamide)-N-(5-((3-imino-3-(isopropylamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3091, 1643, 1199, 759 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.32 (s, 1H, NH), 9.96 (s, 1H, NH), 9.28 - 9.22 (m, 1H, NH), 8.99 (s, 1H, NH), 8.54 (s, 1H, NH), 8.20 - 8.13 (m, 1H, NH), 7.99 (d, J = 8.09 Hz, 2H, ArH), 7.88 - 7.82 (m, 4H, ArH), 7.81 - 7.77 (m, 2H, ArH), 7.56 (d, J = 16.51 Hz, 1H, ArCH=CHAr), 7.49 (d, J = 16.51 Hz, 1H, ArCH=CHAr), 7.37 - 7.32 (m, 1H, pyrroleH), 7.22 - 7.17 (m, 1H, pyrroleH), 7.13~7.09(m, 1H, pyrroleH), 6.98~6.94(m, 1H, pyrroleH), 3.87(s, 3H, pyrroleCH 3 ), 3.82(s, pyrroleCH 3 ), 3.79~3.71(m, RCH(CH 3 )) 3 ), 3.54~3.47(m, 2H, RNHCH 2 CH 2 R), 2.60~2.55(m, 2H, RNHCH 2 CH 2 R), 1.16(s, 3H, RCH(CH 3 )) 3 ), 1.15(s, 3H, RCH(CH 3 LRMS M / z calculation for C 34 H 36 N 8 O 3 604.72 [M] + and measured value 605.1 [M + H] + HRMS m / z for C 34 H 37 O 3 N 8 605.2983 [M + H] + Calculated for, measured value 605.2976 [M + H] + .

[0315] Ia18 (E)-N-(3-imino-3-(isopropylamino)propyl)-4-(4-(4-(4-methoxystyryl)benzamide)-1-methyl-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3269, 1633, 1201, 719 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.3 (s, 1H), 9.95 (s, 1H), 9.21 (d, J = 7.0 Hz, 1H), 8.96 (s, 1H), 8.51 (s, 1H), 8.14 (t, J = 5.0 Hz, 1H), 7.97 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.4 Hz, 2H), 7.37 - 7.36 (m, 2H), 7.34 - 7.30 (m, 2H), 7.23 - 7.20 (m, 2H), 7.18 (d, J = 1.7 Hz, 1H), 7.11 (d, J = 1.7 Hz, 1H), 6.96 (d, J = 1.5 Hz, 1H), 6.91 - 6.87 (m, 1H), 3.87 (s, 3H), 3.82 (s, 3H), 3.81 (S, 3H), 3.77 - 3.70 (m, 1H), 3.51 - 3.49 (m, 2H), 2.58 - 2.55 (m, 2H), 1.15 (d, J = 6.5 Hz, 6H) C 34 H 39 N 7 O 4609.31[M] + Calculated LRMS M / z for, measured value 610.1[M+H] + HRMS m / z C 35 H 40 O 4 N 7 610.3136[M+H] + Calculation for, measured value 610.3137[M+H] + 。

[0316] Ia19(E)-N-(3-Imino-3-(isopropylamino)propyl)-4-(4-(4-(3-methoxystyryl)benzamide)-1-methyl-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3080, 1629, 1199, 719 1 H NMR (500 MHz、DMSO-d 6 ) δ (ppm) 10.3 (s、1H)、9.95 (s、1H)、9.22 (d、J = 8.0 Hz、1H)、8.96 (s、1H)、8.51 (s、1H)、8.14 (t、J = 6.0 Hz、1H)、7.97 (d、J = 8.5 Hz、2H)、7.74 (d、J = 8.5 Hz、2H)、7.38-7.30 (m、4H)、7.24-7.21 (m、2H)、7.18 (d、J = 1.7 Hz、1H)、7.11 (d、J = 1.7 Hz、1H)、6.96 (d、J = 1.7 Hz)、6.91-6.87 (m、1H)、3.87 (s、3H)、3.82 (s、3H)、3.81 (s、3H)、3.52-3.49 (m、2H)、2.58-2.55 (m、2H)、6.37 (d、J = 6.4 Hz、6H) C 34 H 39 N 7 O 4 609.31[M] + Calculated LRMS M / z for, measured value 610.1[M+H] + HRMS m / z C 34 H 40 O 4 N 7 610.3136[M+H] + Calculation for, measured value 610.3130[M+H] + 。

[0317] Ia20(E)-N-(3-(Ethylamino)-3-iminopropyl)-4-(4-(4-(4-methoxystyryl)benzamide)-1-methyl-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3255, 1629, 1199, 719 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.3 (s, 1H), 9.95 (s, 1H), 9.35 (s, 1H), 9.01 (s, 1H), 8.53 (s, 1H), 8.18 (t, J = 8.5 Hz, 1H), 7.97 (d, J = 8.3 Hz, 2H), 7.74 (d, J = 8.3 Hz, 2H), 7.39 - 7.29 (m, 4H), 7.24 - 7.18 (m, 3H), 7.11 (d, J = 1.4 Hz, 1H), 6.95 (d, J = 1.5 Hz, 1H), 6.91 - 6.87 (m, 1H), 3.88 (s, 3H), 8.83 - 3.80 (m, 6H), 3.50 (t, J = 6.1 Hz, 2H), 3.23 - 3.17 (m, 2H), 2.59 (t, J = 6.1 Hz, 2H), 1.14 (t, J = 7.2 Hz, 3H) C 33 H 37 N 7 O 4 595.29[M] + Calculated LRMS M / z for, found 596.3[M + H] + HRMS m / z C 33 H 38 N 7 O 4 596.2980[M + H] + Calculated, found 596.2972[M + H] + 。

[0318] Ia21(E)-N-(3-Imino-3-(isopropylamino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3265, 1670, 1197, 719 1 H NMR (500 MHz, DMSO-d 6) δ (ppm): 10.4 (s, 1H), 9.96 (s, 1H), 9.28 - 9.26 (m, 1H), 9.24 - 9.19 (m, 1H), 8.97 (s, 1H), 8.56 (s, 1H), 8.51 (s, 1H), 8.17 - 8.12 (m, 1H), 8.05 - 7.99 (m, 4H), 7.81 (d, J = 8.4 Hz, 2H), 7.79 - 7.74 (m, 1H), 7.71 - 7.59 (m, 4H), 7.34 (d, J = 1.7 Hz, 1H), 7.18 (d, J = 1.7 Hz, 1H), 7.12 (d, J = 1.7 Hz, 1H), 6.97 (d, J = 1.7 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.79 - 3.73 (m, 2H), 3.53 - 3.47 (m, 2H), 2.59 - 2.55 (m, 1H), 1.16 (d, J = 6.4 Hz, 6H) C 36 H 38 N 8 O 3 630.31[M] + Calculated LRMS M / z for, found 631.0[M+H] + HRMS m / z C 36 H 97 O 3 N 8 631.3140[M+H] + Calculated, found 631.3135[M+H] + .

[0319] Ia22(E)-N-(3-(ethylamino)-3-iminopropyl)-4-(4-(4-(3-methoxystyryl)benzamide)-1-methyl-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3307, 1377, 1128, 950 1H NMR (500 MHz, DMSO-d6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.29 (d, J = 1.8 Hz, 1H), 8.60 (s, 1H), 8.29 (t, J = 5.7 Hz, 1H), 7.07 - 7.00 (m, 4H), 7.84 - 7.76 (m, 3H), 7.71 - 7.60 (m, 4H), 7.35 (d, J = 1.4 Hz, 1H), 7.21 (d, J = 1.4 Hz, 1H), 7.12 (d, J = 1.4 Hz, 1H), 7.00 (d, J = 1.4 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 6H), 3.60 - 3.56 (m, 2H), 3.44 - 3.40 (m, 2H), 3.35 - 3.30 (m, 2H), 0.90 - 0.87 (m, 3H) C 33 H 37 N 7 O 4 595.29[M] + Calculated LRMS M / z for, found 596.3 [M+H] + HRMS m / z C 33 H 38 O 4 N 7 596.2980 [M+H] + Calculated, found 596.2975 [M+H] + 。

[0320] Ia23(E)-N-(5-((5-((3-Imino-3-(isopropylamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-6-(3-methoxystyryl)nicotinamide IR (cm -1 ) 3342, 1379, 950, 653 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.5 (s, 1H), 9.96 (s, 1H), 9.22 (d, J = 7.7 Hz, 1H), 9.09 (s, J = 2.1 Hz, 1H), 8.30 - 8.27 (m, 1H), 8.15 (t, J = 5.7 Hz, 1H), 7.77 (d, J = 16 Hz, 1H), 7.70 (d, J = 8.2 Hz, 1H), 7.43 (d, J = 16 Hz, 1H), 7.37 - 7.32 (m, 2H), 7.30 - 7.26 (m, 2H), 7.18 (d, J = 1.8 Hz, 1H), 7.10 (d, J = 1.8 Hz, 1H), 6.96 (d, J = 1.7 Hz, 1H), 6.95 - 6.92 (m, 1H), 3.88 (s, 3H), 3.82 (s, 6H), 3.78 - 3.73 (m, 1H), 3.53 - 3.48 (m, 2H), 2.57 (t, J = 6.3 Hz, 2H), 1.15 (d, J = 6.4 Hz, 6H) C 33 H 38 N 8 O 4 610.30[M] + Calculated LRMS M / z for, found 611.7[M + H] + HRMS m / z C 33 H 39 O 4 N 8 611.3089[M + H] + Calculated for, found value 611.3086[M + H] + 。

[0321] Ia24(E)-N-(5-((5-((3-(Ethylamino)-3-iminopropyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-6-(4-methoxystyryl)nicotinamide IR (centi -1 ) 3120, 1498, 1257, 655 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.5 (s, 1H), 9.96 (s, 1H), 9.06 (d, J = 2.2 Hz, 1H), 9.00 (s, 1H), 8.52 (s, 1H), 8.27 - 8.24 (m, 1H), 8.18 (t, J = 5.7 Hz, 1H), 7.75 (d, J = 16 Hz, 1H), 7.68 - 7.60 (m, 4H), 7.34 (d, J = 1.7 Hz, 1H), 7.25 (d, J = 16 Hz, 1H), 7.19 (d, J = 1.7 Hz, 1H), 7.11 (d, J = 1.7 Hz, 1H), 7.00 (d, J = 8.9 Hz, 1H), 6.95 (d, J = 1.7 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.81 (s, 3H), 3.52 - 3.47 (m, 2H), 3.22 - 3.18 (m, 2H), 2.60 - 2.58 (m, 2H), 1.14 (t, J = 7.2 Hz, 1H) C 32 H 36 N 8 O 4 596.29[M] + Calculated LRMS M / z for, found 597.3 [M+H] + .

[0322] Ia25 4-(4-((E)-2-(Benz[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-(((Z)-3-(ethylamino)-3-(ethylimino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3317, 2968, 1379, 1128, 950 1H NMR (500 MHz, DMSO-d6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.26 - 9.22 (m, 1H), 8.59 - 8.55 (m, 1H), 8.28 - 8.23 (m, 1H), 8.02 (d, J = 8.4 Hz, 2H), 7.83 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 17 Hz, 1H), 7.62 (d, J = 17 Hz, 1H), 7.35 (d, J = 1.7 Hz, 1H), 7.20 (d, J = 1.7 Hz, 1H), 7.19 (s, 1H), 7.13 (d, J = 1.7 Hz, 1H), 7.09 (s, 1H), 6.99 (s, 1H), 6.97 (d, J = 1.7 Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.49 - 3.45 (m, 4H), 3.23 - 3.18 (m, 2H), 2.75 - 2.71 (m, 2H), 1.21 - 1.16 (m, 6H) C 34 H 37 N 9 O 4 635.30[M] + Calculated LRMS M / z for, found 636.3 [M+H] + HRMS m / z C 34 H 38 O 4 N 9 636.3041[M+H] + Calculated for, found 636.3028 [M+H] + .

[0323] Ia26N-(5-((5-(((Z)-3-(ethylamino)-3-(ethylimino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-6-((E)-3-methoxystyryl)nicotinamide IR (cm -1 ) 2968, 1377, 1128, 950 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.5 (s, 1H), 9.96 (s, 1H), 9.35 (s, 1H), 9.09 (s, 1H), 9.01 (s, 1H), 8.53 (s, 1H), 8.31 - 8.27 (m, 1H), 8.20 - 8.16 (m, 1H), 7.77 (d, J = 16 Hz, 1H), 7.69 (d, J = 8.0 Hz, 1H), 7.43 (d, J = 16 Hz, 1H), 7.37 - 7.32 (m, 2H), 7.30 - 7.27 (m, 2H), 7.19 (d, J = 1.7 Hz, 1H), 7.11 (d, J = 1.7 Hz, 1H), 6.96 - 6.92 (m, 2H), 3.88 (s, 1H), 3.82 (s, 6H), 3.52 - 3.47 (m, 2H), 3.22 - 3.18 (m, 2H), 2.59 (t, J = 6.1 Hz, 2H), 1.14 (t, J = 7.2 Hz, 3H) C 32 H 36 N 8 O 4 596.29[M] + Calculated LRMS M / z for, found 597.0[M+H] + HRMS m / z C 32 H 37 O 4 N 8 597.2932[M+H] + Calculated, found 597.2924[M+H] + 。

[0324] Ia27(E)-N-(3-Imino-3-(methylamino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3091, 1490, 1309, 775 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.96 (s, 1H), 9.44 - 9.39 (m, 1H), 9.28 (d, J = 1.9 Hz, 1H), 8.20 (t, J = 5.8 Hz, 1H), 8.06 - 7.97 (m, 4H), 7.87 - 7.81 (m, 2H), 7.79 - 7.76 (m, 1H), 7.68 - 7.63 (m, 3H), 7.34 (d, J = 1.6 Hz, 1H), 7.19 (d, J = 1.6 Hz, 1H), 7.12 (d, J = 1.6 Hz, 1H), 6.95 (d, J = 1.6 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.49 - 3.48 (m, 2H, H 2 O peak time), 2.80 (d, J = 4.9Hz, 3H), 2.61 - 2.56 (m, 2H) C 34 H 34 N 8 O 3 602.70[M] + Calculated LRMS M / z for, measured value 603.3[M + H] + HRMS m / z C 34 H 35 N 8 O 3 603.2827[M + H] + Calculation for, measured value 603.2821[M + H] + .

[0325] Ia28(E)-N-(3-Imino-3-(methoxyamino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3258, 3076, 2938, 2818, 2690, 2160, 2037, 1979, 1773, 1667, 1632, 1580, 1535, 1464, 1435, 1404, 1348, 1263, 1196, 1182, 1130, 1061, 1015, 968, 951, 895, 833, 797, 770, 750, 719, 704. 11H NMR (500 MHZ, DMSO-d 6 ) δ (ppm) 10.37 (s, 1H), 9.97 (s, 1H), 9.29 (d, 1H, J = 1.8 Hz), 8.60 (d, 1H, J = 1.35 Hz), 8.23 (t, 1H, 5.35 Hz) 8.08 - 8.00 (m, 5H), 7.86 - 7.77 (m, 4H), 7.83 (d, 2H, J = 8.35 Hz), 7.79 (t, 1H, J = 7.68 Hz), 7.73 - 7.61 (m, 3H), 7.36 (d, 1H, J = 1.1 Hz), 7.21 (d, 1H, J = 1.41 Hz), 7.13 (d, 1H, J = 1.36), 6.96 (d, 1H, J = 1.0 Hz), 3.89 (s, 3H), 3.83 (s, 3H), 3.73 (s, 1H), 3.49 (q, 2H, J = 5.9 Hz), 2H triplet is hidden under the DMSO peak at 2.53 - 2.50 ppm and cannot be seen C 34 H 34 N 8 O 4 618.70 [M] + Calculated LRMS M / z for, found 619.4 [M + H] +.

[0326] Ia29(E)-N-(3-imino-3-(methoxyamino)propyl)-4-(4-(4-(3-methoxystyryl)benzamide)-1-methyl-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxamide IR (centi -1 ) 3280, 1670, 1199, 721 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.3 (s, 1H), 9.95 (s, 1H), 7.98 (d, J = 8.3 Hz, 2H), 7.74 (d, J = 8.3 Hz, 2H), 7.38 - 7.30 (m, 4H), 7.24 - 7.18 (m, 3H), 7.12 - 7.09 (m, 1H), 6.94 - 6.87 (m, 2H), 3.87 (s, 3H), 3.81 (s, 6H), 3.67 (s, 3H), 3.54 - 3.50 (m, 2H), 2.44 - 2.37 (m, 2H) C 32 H 35 N 7 O 5 597.68[M] + Calculated LRMS M / z for, found 598.6[M + H] + .

[0327] Ia30(E)-4-(4-(2-(Benz[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((3-imino-3-(methoxyamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3313, 1637, 1199, 798 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.95 (s, 1H), 8.11 (s, 3H), 8.02 (d, J = 8.3 Hz, 2H), 7.82 (d, J = 8.3 Hz, 2H), 7.70 (d, J = 16 Hz, 1H), 7.61 (d, J = 16 Hz, 1H), 7.36 - 7.34 (m, 1H), 7.21 - 7.19 (m, 1H), 7.12 - 7.09 (m, 1H), 6.93 - 6.91x(m, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.68 (s, 3H), 3.54 - 3.49 (m, 2H), 2.46 - 3.37 (m, 2H) C 31 H 31 N 9 O 5 609.65[M]+ Calculated LRMS M / z for, measured value 610.5 [M+H] + 。

[0328] Ia31(E)-6-(4-(Dimethylamino)styryl)-N-(5-((5-((3-Imino-3-(methoxyamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)nicotinamide Infrared (centi -1 ) 3111, 1664, 1128, 721 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.5 (s, 1H), 9.97 (s, 1H), 9.06 (s, 1H), 8.28 (d, J = 8.2 Hz, 1H), 8.17 (s, 1H), 7.73 (d, J = 16 Hz, 1H), 7.64 (d, J = 7.8 Hz, 1H), 7.54 (d, J = 8.6 Hz, 2H), 7.35 (s, 1H), 7.21 (s, 1H), 7.16 - 7.10 (m, 2H), 6.92 (s, 1H), 6.76 (d, J = 8.6 Hz, 2H), 3.88 (s, 3H), 3.81 (s, 3H), 3.69 (s, 1H), 3.47 - 3.44 (m, 2H), 2.98 (s, 6H), 2.46 - 2.43 (m, 2H); C 32 H 37 N 9 O 4 611.71 [m] + Calculated LRMS M / z for, measured value 612.7 [m+H] + 。

[0329] Ia32(E)-6-(4-(Dimethylamino)styryl)-N-(5-((5-((3-Imino-3-(nonylamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)nicotinamide Infrared (cm -1) 2926, 2856, 1664, 1577, 1527, 1433, 1365, 1288, 1168, 1128, 798, 721 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.43 (1H, s), 9.94 (1H, s), 9.30 (2H, bs), 9.04 - 8.99 (3H, m), 8.50 (2H, s), 8.24 - 8.20 (2H, m), 8.14 (1H, t, J = 6 Hz), 7.71 - 7.52 (6H, m), 7.33 (1H, s), 7.17 - 7.07(5H, m), 6.97 (1H, s), 6.77 - 6.73 (2H, m), 3.87 (3H, s), 3.81 (3H, s), 3.51 - 3.48 (2H, m), 3.16 - 3.13 (2H, m), 2.97 (6H, s), 2.62 - 2.60 (2H, m), 1.51 - 1.48 (2H, m), 1.24 - 1.20 (12H, m), 0.85 - 0.81 (3H, m) C 40 H 53 N 9 O 3 LRMS m / z calculated for 707.4, found 708.1 [M + H] + HRMS m / z C 40 H 54 N 9 O 3 708.4344 [M + H] + Calculated for, found 715.4068 [M + H] + 。

[0330] Ia33 6 - ((E) - 4 - (dimethylamino)styryl) - N - (5 - ((5 - ((E) - 3 - (heptylamino) - 3 - (heptylimino)propyl)carbamoyl) - 1 - methyl - 1H - pyrrol - 3 - yl)carbamoyl) - 1 - methyl - 1H - pyrrole - 3 - yl)nicotinamide IR (cm -1) 3248, 3088, 2927, 2856, 1643, 1573, 1529, 1435, 1402, 1367, 1313, 1286, 1265, 1199, 1170, 1128, 1064, 1002, 831, 775, 719 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.45 (1H, s), 9.96, (1H, s), 9.24 - 9.20 (2H, m), 9.04 (1H, s), 8.56 - 8.51 (3H, m), 8.25 - 8.21(4H, m), 7.72 - 7.61 (2H, m), 7.55 - 7.51 (3H, m), 7.34 (1H, s), 7.17 - 7.07 (5H, m), 6.98 (1H, s), 6.77 - 6.74 (3H, m), 3.87 (3H, s), 3.81 (3H, s), 3.49 - 3.45 (2H, m), 3.39 - 3.35 (2H, m), 3.16 - 3.12 (2H, m), 2.97 (6H, s), 2.74 - 2.70 (2H, m), 1.54 - 1.50 (4H, m), 1.30 - 1.23 (16H, m), 0.88 - 0.83 (6H) C 45 H 63 N 9 O 3 777.5[M] + LRMS M / z calculated for, found 778.0[M + H] + HRMS m / z C 45 H 64 N 9 O 3 778.5127[M + H] + Calculated for, found 778.5118[M + H] + 。

[0331] Ia34(E)-N-(3-(Butylamino)-3-iminopropyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (cm -1) 2962.66, 2872.01, 1670.35, 1635.64, 1577.77, 1533.41, 1462.04, 1435.04, 1402.25, 1390.68, 1261.45, 1197.79, 1170.79, 1126.43, 1062.78, 1014.56, 975.98, 960.55, 894.97, 873.75, 837.11, 792.74, 756.1, 721.38, 704.02, 692.44, 607.58 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.36 (1H, s), 9.96 (1H, s), 9.32 (1H, s), 9.29 (1H, bs), 9.01 (1H, bs), 8.60 - 8.54 (3H, m), 8.18 (1H, t, J = 6Hz), 8.08 - 7.99 (5H, m), 7.84 - 7.77 (4H, m), 7.71 - 7.61 (4H, m), 7.35 (1H, s), 7.18 (1H, s), 7.13 (1H, s), 6.98 (1H, s), 3.89 (3H, s), 3.83 (3H, s), 3.52 - 3.49 (2H, m), 3.17 - 3.14 (2H, m), 2.62 - 2.59 (2H, m), 1.52 - 1.49 (2H, m), 1.34 - 1.29 (2H, m), 0.90 - 0.89 (3H, m); C 37 H 40 N 8 O 3 644.3 [M] + Calculated LRMS M / z for, found 645.8 [M + H] + HRMS m / z C 37 H 41 N 8 O 3 645.3296 [M + H] + Calculated for, found 645.3285 [M + H] + 。

[0332] Ia35(E)-N-(3-imino-3-(pentylamino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared -1 3259, 3093, 2964, 1670, 1637, 1577, 1560, 1521, 1458, 1436, 1382, 1265, 1195, 1176, 1128, 1062, 966, 894, 831, 798, 771, 750, 719, 628 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.36 (1H, s), 9.95 (1H, s), 9.33 (1H, s), 9.28 (1H, bs), 9.01 (1H, bs), 8.59 - 8.54 (3H, m), 8.16 (1H, t, J = 6Hz), 8.05 - 7.97 (5H, m), 7.82 - 7.75 (4H, m), 7.70 - 7.60 (4H, m), 7.34 (1H, s), 7.17 (1H, s), 7.11 (2H, s), 6.97 (1H, s), 3.88 (3H, s), 3.82 (3H, s), 3.52 - 3.48 (2H, m), 3.17 - 3.13 (2H, m), 2.62 - 2.59 (2H, m), 1.52 - 1.50 (2H, m), 1.27 - 1.25 (4H, m), 0.85 - 0.82 (3H, m) C 38 H 42 N 8 O 3 658.3[M] + Calculated LRMS M / z for, found 659.0[M + H] + HRMS m / z C 38 H 42 N 8 O 3 659.3453[M + H] + Calculated, found 659.3443[M + H] + .

[0333] Ia36(E)-N-(3-imino-3-(nonylamino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared -1 3259, 3088, 2929, 2856, 1633, 1579, 1531, 1462, 1433, 1402, 1263, 1197, 1178, 1130, 1064, 968, 894, 831, 798, 773, 748, 719 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.35 (1H, s), 9.94 (1H, s), 9.31 - 9.26 (3H, m), 8.99 (2H, s), 8.56 - 8.51 (4H, m), 8.15 (2H, t, J = 6 Hz), 8.04 - 8.00 (5H, m), 7.82 - 7.74 (5H, m), 7.66 - 7.63 (3H, m), 7.34 (1H, s), 7.17 (2H, s), 7.12 (1H, s), 6.98 (1H, s), 3.88 (3H, s), 3.82 (3H, s), 3.51 - 3.48 (2H, m), 3.16 - 3.13 (2H, m), 2.62 - 2.60 (2H, m), 1.51 - 1.48 (2H, m), 1.24 - 1.20 (12H, m), 0.85 - 0.81 (3H, m) C 42 H 50 N 8 O 3 714.4[M] + Calculated LRMS M / z for, found 715.1[M + H] + HRMS m / z calculated value: C 42 H 51 N 8 O 3 715.4079, found: 715.4068 [M + H] + .

[0334] Ia37 N-((Z)-3-(Heptylamino)-3-(heptylimino)propyl)-1-methyl-4-(1-methyl-4-(4-((E)-2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared -1 3253, 3088, 2929, 2858, 1633, 1581, 1462, 1435, 1402, 1263, 1197, 1174, 1128, 1060, 1016, 968, 894, 829, 771, 750, 719, 624 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.36, (1H, s), 9.27 - 9.21 (3H, m), 8.56 - 8.51 (4H, m), 8.224 - 8.21 (1H, m), 8.05 - 8.01 (6H, m), 7.84 - 7.75 (4H, m), 7.68 - 7.64 (4H, m), 7.35 (1H, s), 7.19 - 7.09 (4H, m), 7.01 - 6.98 (2H, m), 3.89 (3H, s), 3.83 (3H, s), 3.49 - 3.45 (2H, m), 3.40 - 3.36 (2H, m), 3.17 - 3.14 (2H, m), 2.75 - 2.71 (2H, m), 1.56 - 1.52 (4H, m), 1.29 - 1.24 (16H), 0.87 - 0.84 (6H, m) C 47 H 60 N 8 O 3 784.4[M] + Calculated LRMS M / z for, found 785.0[M + H] + HRMS m / z C 47 H 61 N 8 O 3 785.4861[M + H] + Calculated for, found 785.4851[M + H] + .

[0335] Ia38 N-((E)-3-(butylamino)-3-(butylimino)propyl)-1-methyl-4-(1-methyl-4-(4-((E)-2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared -1 3265, 3080, 2956, 1633, 1531, 1435, 1402, 1384, 1263, 1197, 1178, 1130, 1062, 968, 831, 798, 771, 750, 719, 707, 605 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.35 (1H, s), 9.96 (1H, s), 9.27 (1H, s), 9.22 (1H, bs), 8.56 - 8.52 (3H, m), 8.24 (1H, t, J = 6Hz), 8.05 - 8.00 (5H, m), 7.82 - 7.75 (4H, m), 7.69 - 7.60 (4H, m), 7.34 (1H, s), 7.17 (1H, s), 7.11 (1H, s), 6.98 (1H, s), 3.88 (3H, s), 3.82 (3H, s), 3.48 - 3.46 (2H, m), 3.41 - 3.38 (2H, m), 3.17 - 3.14 (2H, m), 2.74 - 2.70(2H, m), 1.56 - 1.49(4H, m), 1.35 - 1.28(4H, m), 0.91 - 0.86(6H, m) C 41 H 48 N 8 O 3 700.8[M] + Calculated LRMS M / z for, found 701.9[M + H] + HRMS m / z C 41 H 49 N 8 O 3 701.3922[M + H] + Calculated for, found 701.3910[M + H] + .

[0336] Ia39 N-(5-((5-(((E)-3-(Butylamino)-3-(butylimino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-6-((E)-4-(dimethylamino)styryl)nicotinamide Infrared (cm -1 ) 3251, 3091, 2956, 2933, 1653, 1573, 1527, 1458, 1435, 1404, 1365, 1365, 1313, 1288, 1265, 1166, 1126, 1126, 1064, 1002, 964, 945, 831, 812, 798, 777, 719, 661, 623 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.48 (1H, s), 9.96, (1H, s), 9.24 - 9.22 (2H, m), 9.04 (1H, s), 9.56 - 9.54 (1H, m), 8.29 - 8.23 (2H, m), 7.75 - 7.66 (2H, m), 7.55 - 7.52 (2H, m), 7.34 (1H, s), 7.18 - 7.10 (3H, m), 6.97 (1H, s), 6.78 - 6.75 (2H, m), 3.88 (3H, s), 3.82 (3H, s), 3.48 - 3.44 (2H, m), 3.40 - 3.36 (2H, m), 3.17 - 3.13 (2H, m), 2.98 (6H, s), 2.74 - 2.70 (2H, m), 1.57 - 1.48 (4H, m), 1.36 - 1.25 (4H, m), 0.90 - 0.84 (6H, m) C 39 H 51 N 9 O 3 693.4 [M] + Calculated LRMS M / z for, found 694.0 [M + H] + HRMS m / z C 39 H 52 N 9 O 3 694.4188 [M + H] + Calculated for, found 694.4178 [M + H] + 。

[0337] Ia40(E)-4-(4-(2-(Benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((12-imino-2,5,8-trioxa-11-azatetradecan-14-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2- Infrared (centi -1 ) 3109, 1629, 1199, 721 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.95 (s, 1H), 9.48 (s, 1H), 9.07 (s, 1H), 8.60 (s, 1H), 8.15 (t, J = 5.5 Hz, 1H), 8.11 (s, 3H), 8.02 (d, J = 8.3 Hz, 2H), 7.82 (d, J = 8.3 Hz, 2H), 7.70 (d, J = 17 Hz, 1H), 7.63 (d, J = 17 Hz, 1H), 7.34 (d, J = 1.5 Hz, 1H), 7.18 (d, J = 1.6 Hz, 1H), 7.12 (d, J = 1.6 Hz, 1H), 6.97 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.58 - 3.48 (m, 14H), 3.23 (s, 3H), 2.63 - 2.59 (m, 2H) C 37 H 43 N 9 O 7 725.33[M] + Calculated LRMS M / z for, found 726.7[M + H] + HRMS m / z C 37 H 44 N 9 O 7 726.3358[M + H] + Calculated, found 726.3354[M + H] + 。

[0338] Ia41(E)-N-(3-imino-3-((2-(4-methylpiperazin-1-yl)ethyl)amino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3097, 1629, 1182, 719 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.96 (s, 1H), 9.27 (s, 1H), 9.08 (s, 1H), 8.62 (s, 1H), 8.56 (s, 1H), 8.18 (t, J = 5.8 Hz, 1H), 8.04 - 8.00 (m, 4H), 7.82 (d, J = 8.5 Hz, 2H), 7.78 - 7.74 (m, 1H), 7.68 - 7.62 (m, 3H), 7.33 (d, J = 1.3 Hz, 1H), 7.17 (d, J = 1.5 Hz, 1H), 7.14 (d, J = 1.3 Hz, 1H), 7.01 - 6.99 (m, 1H), 3.88 (s, 3H), 3.82(s, 3H), 3.52 - 3.49(m, 7H), 3.40 - 3.34(m, 5H), 3.31 - 3.28(m, 2H), 2.99 - 2.93(m, 2H), 2.76(s, 3H) C 40 H 46 N 10 O 3 714.38[M] + Calculated LRMS M / z for, found 715.0[M+H] + HRMS m / z C 40 H 47 N 10 O 3 715.3827[M+H] + Calculated for, found 715.3825[M+H] + .

[0339] Ia42(E)-4-(4-(2-(Benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((3-imino-3-((2-(4-methylpiperazin-1-yl)ethyl)amino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2- Infrared (centi -1 ) 3032, 1629, 1180, 705 1H NMR (500 MHz, DMSO-d6) δ (ppm) 10.4 (s, 1H), 9.27 (s, 1H), 9.10 (s, 1H), 8.64 (s, 1H), 8.18 (t, J = 5.5 Hz, 1H), 8.11 (s, 3H), 8.01 (d, J = 8.3 Hz, 2H), 7.82 (d, J = 8.3 Hz, 2H), 7.70 (d, J = 17 Hz, 1H), 7.61 (d, J = 17 Hz, 1H), 7.33 (d, J = 1.5 Hz, 1H), 7.17 (d, J = 1.6 Hz, 1H), 7.14 (d, J = 1.6 Hz, 1H), 6.99 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.39 - 3.33 (m, 5H), 3.32 - 3.28 (m, 3H), 3.00 - 2.94 (m, 2H), 2.91 - 2.83 (m, 2H), 2.76 (s, 3H), 2.65 - 2.60 C 37 H 43 N 11 O 4 705.35[M] + Calculated LRMS M / z for, found 705.9[M+H] + HRMS m / z C 37 H 44 N 11 O 4 706.3572[M+H] + Calculated, found 706.3564[M+H] + 。

[0340] Ia43(E)-4-(4-(2-(Benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((3-imino-3-(phenethylamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3255, 1627, 1201, 698 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.27 (s, 1H), 9.10 (s, 1H), 8.64 (s, 1H), 8.18 (t, J = 5.5 Hz, 1H), 8.11 (s, 3H), 8.01 (d, J = 8.3 Hz, 2H), 7.82 (d, J = 8.3 Hz, 2H), 7.70 (d, J = 17 Hz, 1H), 7.61 (d, J = 17 Hz, 1H), 7.33 (d, J = 1.5 Hz, 1H), 7.17 (d, J = 1.6 Hz, 1H), 7.14 (d, J = 1.6 Hz, 1H), 6.99 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.39 - 3.33 (m, 5H), 3.32 - 3.28 (m, 3H), 3.00 - 2.94 (m, 2H), 2.91 - 2.83 (m, 2H), 2.76 (s, 3H), 2.65 - 2.60 C 38 H 37 N 9 O 4 683.30[M] + Calculated LRMS M / z for, found 684.4 [M + H] + HRMS m / z C 38 H 38 N 9 O 4 684.3041[M + H] + Calculated, found 684.3038 [M + H] + 。

[0341] Ia44(E)-N-(3-imino-3-((2-(tetrahydro-2H-pyran-4-yl)ethyl)amino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 2933, 1674, 1201, 835 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.95 (s, 1H), 9.29 (d, J = 1.9 Hz, 1H), 9.03 (s, 1H), 8.60 (s, 1H), 8.55 (s, 1H), 8.16 (t, J = 5.8 Hz, 1H), 8.07 - 7.99 (m, 5H), 7.84 - 7.76 (m, 4H), 7.69 - 7.61 (m, 3H), 7.34 (d, J = 1.5 Hz, 1H), 7.16 (d, J = 1.6 Hz, 1H), 7.11 (d, J = 1.6 Hz, 1H), 7.00 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.53 - 3.49 (m, 2H), 3.22 - 3.16 (m, 4H), 2.62 - 2.58 (m, 2H), 1.55 - 1.50 (m, 3H), 1.49 - 1.42 (m, 3H), 1.19 - 1.09 (m, C 40 H 44 N 8 O 4 700.35[M] + Calculated LRMS M / z for, found 701.4[M+H] + HRMS m / z C 40 H 45 O 4 N 8 701.3558[M+H] + Calculated, found 701.3548[M+H] + 。

[0342] Ia45(E)-4-(4-(2-(Benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((3-imino-3-((2-(tetrahydro-2H-pyran-4-yl)ethyl)amino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2 Infrared (centi -1 ) 3084, 1629, 1199, 798 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.95 (s, 1H), 9.31 (s, 1H), 9.03 (s, 1H), 8.54 (s, 1H), 8.16 (t, J = 5.9 Hz, 1H), 8.10 (s, 3H), 8.01 (d, J = 8.3 Hz, 2H), 7.81 (d, J = 8.3 Hz, 2H), 7.70 (d, J = 16 Hz, 1H), 7.61 (d, J = 16 Hz, 1H), 7.34 (d, J = 1.2 Hz, 1H), 7.15 (d, J = 1.5 Hz, 1H), 7.11 (d, J = 1.2 Hz, 1H), 7.00 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.80 - 3.77 (m, 2H), 3.52 - 3.49 (m, 2H), 3.20 - 3.18 (m, 2H), 2.62 - 2.58 (m, 2H), 1.56 - 1.49 (m, 4H), 1.49 - 1.43 (m, 3H), 1.25 - 1.11 (m, 4H) C 37 H 41 N 9 O 5 691.32[M] + Calculated LRMS M / z for, found 692.3 [M+H] + C 37 H 42 O 5 N 9 692.3303[M+H] + Calculated HRMS m / z for, found 692.3300 [M+H] +.

[0343] Ia46(E)-4-(4-(2-(Benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((3-((3-(dimethylamino)propyl)amino)-3-iminopropyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3290, 1676, 1448, 1022 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.95 (s, 1H), 9.18 (s, 1H), 8.68 (s, 1H), 8.22 (s, 1H), 8.01 (d, J = 8.5 Hz, 2H), 7.82 (d, J = 8.5 Hz, 2H), 7.70 (d, J = 16 Hz, 2H), 7.61 (d, J = 16 Hz, 2H), 7.33 (s, 1H), 7.20 - 7.12 (m, 2H), 7.03 - 6.97 (m, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.57 - 3.50 (m, 2H), 3.25 - 3.24 (m, 2H), 3.06 - 3.03 (m, 2H), 2.76 - 2.75(m, 6H), 2.61 - 2.58(m, 2H), 1.89 - 1.86(m, 2H) C 35 H 40 N 10 O 4 664.32[M] + Calculated LRMS M / z for, found 665.3 [M + H] + HRMS m / z C 35 H 41 O 4 N 10 665.3307[M + H] + Calculated for, found 665.3297 [M + H] + 。

[0344] Ia47(E)-N-(3-imino-3-((2-thiomorpholinoethyl)amino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3319, 1629, 1305, 831 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.96 (s, 1H), 9.54 (s, 1H), 9.37 (s, 1H), 9.28 (s, 1H), 8.84 (s, 1H), 8.58 (s, 1H), 8.25 (s, 1H), 8.05 - 7.99 (m, 4H), 7.82 (d, J = 8.2 Hz, 2H), 7.79 - 7.75 (m, 1H), 7.69 - 7.60 (3H), 7.34 (s, 1H), 7.16 (s, 1H), 7.13 (s, 1H), 7.01 (s, 1H), 3.92 - 3.90 (m, 2H), 3.88 (s, 3H), 3.83(s, 3H), 3.74 - 3.72(m, 2H), 3.61 - 3.57(m, 2H), 3.55 - 3.48(m, 4H), 2.95 - 2.81(m, 4H), 2.64 - 2.60(m, 2H) C 39 H 43 N 9 O 3 S 717.32[M] + Calculated LRMS M / z for, found 718.6 [M+H] + C 39 H 44 N 9 O 3 S 718.3282[M+H] + Calculated HRMS m / z for, found 718.3283 [M+H] +.

[0345] Ia48(E)-N-(3-imino-3-(phenethylamino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3072, 1629, 1178, 719 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.37 (s, 1H), 9.97 (s, 1H), 9.51 (s, 1H), 9.29 - 9.25 (m, 1H), 9.09 (s, 1H), 8.65 (s, 1H), 8.59 - 8.55 (m, 1H), 8.23 - 8.17 (m, 1H), 8.06 - 7.99 (m, 4H), 7.82 (d, J = 8.1 Hz, 2H), 7.80 - 7.73 (m, 1H), 7.72 - 7.59 (m, 3H), 7.36 - 7.20 (m, 6H), 7.20 - 7.17 (m, 1H), 7.14 - 7.10 (m, 1H), 7.02 - 6.98 (m, 1H), 3.87 (s, 3H), 3.83 (s, 3H), 3.52 - 3.40 (m, 4H), 2.89 - 2.82 (m, 2H), 2.64 - 2.57 (m, 2H) C 41 H 40 N 8 O 3 LRMS M / z calculated for 692.82[M], found 693.7[M+H] + HRMS m / z C 41 H 41 N 8 O 3 693.3296[M+H] + calculated, found 693.3291[M+H] + .

[0346] Ia49 (E) 6-(4-(Dimethylamino)styryl)-N-(5-((5-((3-imino-3-(phenethylamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)nicotinamide Infrared (centi -1 ) 3213, 2922, 1676, 1074 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.45 (s, 1H), 9.96 (s, 1H), 9.48 (bs, 1H), 9.09 - 9.02 (m, 2H), 8.63 (s, 1H), 8.29 - 8.23 (m, 1H), 8.19 (t, J = 5.9 Hz, 1H), 7.72 (d, J = 16.0 Hz, 1H), 7.65 (d, J = 8.3 Hz, 1H), 7.54 (d, J = 8.5 Hz, 2H), 7.36 - 7.20 (m, 6H), 7.20 - 7.16 (m, 1H), 7.15 - 7.06 (m, 2H), 7.02 - 6.99 (m, 1H), 6.76 (d, J = 8.6 Hz, 2H), 3.87 (s, 3H), 3.82 (s, 3H), 3.49 (d, J = 6.4 Hz, 2H), 3.43 (d, J = 7.5 Hz, 2H), 2.98 (s, 6H), 2.87 - 2.83 (m, 2H), 2.61 - 2.57 (m, 2H) C 39 H 43 N 9 O 3 Calculated LRMS M / z for 685.83[M], found 686.6[M+H] + .

[0347] Ia50 N-((Z)-3-(Ethylamino)-3-(ethylimino)propyl)-1-methyl-4-(1-methyl-4-(4-((E)-2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3244, 1674, 1174, 1126, 1026, 719 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm): 10.36 (s, 1H), 9.97 (s, 1H), 9.26 (d, J = 2.3 Hz, 1H), 9.25 - 9.22 (m, 1H), 8.59 - 8.53 (m, 2H), 8.24 (t, J = 6.1 Hz, 1H), 8.06 - 7.98 (m, 4H), 7.82 (d, J = 8.5 Hz, 2H), 7.78 - 7.73 (m, 1H), 7.71 - 7.58 (m, 3H), 7.35 (d, J = 2.0 Hz, 1H), 7.19 (d, J = 2.0 Hz, 1H), 7.12 (d, J = 2.0 Hz, 1H), 6.96 (d, J = 1.8 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.48 - 3.42 (m, 4H), 2.73 - 2.69 (m, 2H), 2.52 - 2.51 (m, 2H), 1.19 (t, J = 7.2 Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H), C 37 H 40 N 8 O 3 LRMS M / z calculated for 644.78[M], found 645.4[M+H] + .

[0348] Ia51 6-((E)-4-(Dimethylamino)styryl)-N-(5-((5-((Z)-3-(Ethylamino)-3-(ethylimino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)nicotinamide Infrared (centi -1 ) 3234, 1637, 1575, 1126, 719 11H NMR (500 MHz, DMSO) δ 10.48 (s, 1H), 9.98 (s, 1H), 9.29 (s, 1H), 9.05 (s, 1H), 8.63 (s, 1H), 8.28 - 8.25 (m, 2H), 7.72 (d, J = 15.1 Hz, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.54 (d, J = 8.9 Hz, 2H), 7.37 - 7.33 (m, 1H), 7.22 - 7.18 (m, 1H), 7.15 - 7.09 (m, 2H), 6.96 (d, J = 2.0 Hz, 1H), 6.76 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H), 3.82 (s, 3H), 3.48 - 3.43 (m, 4H), 3.21 (t, J = 6.3 Hz, 2H), 2.75 - 2.71 (m, 2H), 1.20 - 1.13 (m, 6H). C 35 H 43 N 9 O 3 Calculated LRMS M / z for 637.79[M], found 638.4[M + H] +.

[0349] Ia52 (E) 6-(4-(Dimethylamino)styryl)-N-(5-((5-((3-imino-3-((2-thiomorpholinoethyl)amino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)nicotinamide 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.45 (s, 1H), 9.96 (s, 1H), 9.54 - 9.44 (m, 1H), 9.36 (s, 1H), 9.06 - 9.02 (m, 1H), 8.83 (s, 1H), 8.28 - 8.21 (m, 2H), 7.72 (d, J = 15.9 Hz, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.54 (d, J = 8.6 Hz, 2H), 7.35 - 7.31 (m, 1H), 7.18 - 7.08 (m, 3H), 7.02 - 6.99 (m, 1H), 6.76 (d, J = 8.6 Hz, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 3.74 - 3.72 (m, 2H), 3.61 - 3.48 (m, 6H), 2.98 (s, 6H), 2.87 - 2.82 (m, 4H), 2.62 - 2.58 (m, 2 C 37 H 46 N 10 O 3 Calculated LRMS M / z for S 710.90[M], found 711.9[M+H] + 。

[0350] Ia53 4-(4-((E)-3-Methoxystyryl)benzamide)-1-methyl-N-(1-methyl-5-((E)-3-(methylamino)-3-(methylimino)propyl)carbamoyl)-1H-pyrrol-3-yl)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3277, 1637, 1433, 1199 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.32 (s, 1H), 9.96 (s, 1H), 9.36 - 9.32 (m, 1H), 8.62 - 8.57 (m, 1H), 8.28 - 8.25 (m, 1H), 7.97 (d, J = 8.5 Hz, 2H), 7.74 (d, J = 8.5 Hz, 2H), 7.39 - 7.29 (m, 4H), 7.25 - 7.18 (m, 3H), 7.12 (s, 1H), 6.95 (s, 1H), 6.89 (d, J = 7.8 Hz, 1H), 3.88 (s, 3H), 3.84 - 3.79 (m, 6H), 3.49 - 3.44 (m, 2H), 3.02 (d, J = 4.9 Hz, 3H), 2.78 (d, J = 4.9 Hz, 3H), 2.72 (t, J = 6.9 Hz, 2H) C 33 H 37 N 7 O 4 LRMS M / z calculated for 595.29[M], found 596.3[M+H] + 。

[0351] Ia54 6-((E)-4-Methoxystyryl)-N-(1-methyl-5-((1-methyl-5-(((E)-3-(methylamino)-3-(methylimino)propyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)nicotinamide IR (cm -1 ) 3088, 1662, 1197, 1172, 1126, 719 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.48 (s, 1H), 9.97 (s, 1H), 9.37 - 9.33 (m, 1H), 9.09 - 9.05 (m, 1H), 8.63 - 8.59 (m, 1H), 8.30 - 8.24 (m, 2H), 7.76 (d, J = 16.0 Hz, 1H), 7.66 (m, 3H), 7.36 - 7.32 (m, 1H), 7.25 (d, J = 16.2 Hz, 1H), 7.22 - 7.18 (m, 1H), 7.13 - 7.09 (m, 1H), 7.00 (d, J = 8.9 Hz, 2H), 6.96 - 6.93 (m, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.81 (s, 3H), 3.51 - 3.43 (m, 2H), 3.02 (d, J = 4.7 Hz, 3H), 2.78 (d, J = 5.0 Hz, 3H), 2.72 (t, J = 6.6 Hz, 2H) C 32 H 36 N 8 O 4 LRMS M / z calculated for 596.29[M], found 597.4[M+H] + 。

[0352] Ia55 (E) N-(5-((5-((3-Imino-3-(methylamino)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-6-(4-methoxystyryl)nicotinamide Infrared (centi -1 ) 3190, 1688, 1172, 1126, 719 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.47 (s, 1H), 9.96 (s, 1H), 9.41 (s, 1H), 9.09 - 9.04 (m, 2H), 8.51 (s, 1H), 8.28 - 8.23 (m, 1H), 8.22 - 8.19 (m, 1H), 7.75 (d, J = 16.0 Hz, 1H), 7.69 - 7.62 (m, 3H), 7.36 - 7.32 (m, 1H), 7.25 (d, J = 16.0 Hz, 1H), 7.21 - 7.18 (m, 1H), 7.12 - 7.09 (m, 1H), 7.00 (d, J = 8.9 Hz, 2H), 6.96 - 6.92 (m, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.82 (s, 3H), 3.50 - 3.48 (m, 2H), 2.80 (d, J = 4.9 Hz, 3H), 2.59 (t, J = 6.6 Hz, 2H) C 31 H 34 N 8 O 4 Calculated LRMS M / z for 582.27[M], found 583.3[M+H] +.

[0353] Ia56 (E) N-(3-Imino-3-(methylamino)propyl)-4-(4-(4-(3-methoxystyryl)benzamide)-1-methyl-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3250, 1629, 1431, 1199, 686 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.32 (s, 1H), 9.95 (s, 1H), 9.42 - 9.39 (m, 1H), 9.05 (s, 1H), 8.51 (s, 1H), 8.20 (t, J = 5.7 Hz, 1H), 7.97 (d, J = 8.5 Hz, 2H), 7.74 (d, J = 8.5 Hz, 2H), 7.39 - 7.29 (m, 4H), 7.25 - 7.17 (m, 3H), 7.14 - 7.10 (m, 1H), 6.96 - 6.92 (m, 1H), 6.92 - 6.86 (m, 1H), 3.88 (s, 3H), 3.84 - 3.79 (m, 6H), 3.51 - 3.48 (m, 2H), 2.80 (d, J = 5.0 Hz, 3H), 2.59 (t, J = 6.6 Hz, 2H) C 32 H 35 N 7 O 4 LRMS M / z calculated for 581.68[M], found 582.3[M+H] + 。

[0354] Ia57 N-((Z)-3-((2,2-difluoroethyl)amino)-3-((2,2-difluoroethyl)imino)propyl)-1-methyl-4-(1-methyl-4-(4-((E)-2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3209, 1651, 1118, 719 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.36 (s, 1H), 10.17 (t, J = 6.3 Hz, 1H), 9.97 (s, 1H), 9.44 (t, J = 5.8 Hz, 1H), 9.28 (d, J = 2.3 Hz, 1H), 8.60 (s, 1H), 8.27 (t, J = 6.3 Hz, 1H), 8.07 - 7.99 (m, 4H), 7.85 - 7.74 (m, 3H), 7.69 - 7.62 (m, 3H), 7.35 (d, J = 2.0 Hz, 1H), 7.20 (d, J = 2.0 Hz, 1H), 7.12 (d, J = 2.0 Hz, 1H), 6.97 (d, J = 2.0 Hz, 1H), 6.40 - 6.13 (m, 2H), 4.04 - 3.94 (m, 4H), 3.88 (s, 3H), 3.82 (s, 3H), 3.47 (q, J = 6.6 Hz, 2H), 2.84 (t, J = 6.9 Hz, 2H) 19 F NMR (471 MHz, DMSO-d 6 ) δ(ppm) -74.38 (TFA), -122.15 (dt, J = 54.6, 15.6 Hz), -122.90 (dt, J = 54.6, 15.6 Hz) C 37 H 36 F 4 N 8 O 3 LRMS M / z calculated for 716.74[M], found 717.3[M+H] +.

[0355] Ia58 (E) N-N-(3-imino-3-((2-methoxyethyl)amino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 2360, 1193, 1116, 839 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.35 (s, 1H), 9.95 (s, 1H), 9.48 (s, 1H), 9.26 (d, J = 2.1 Hz, 1H), 9.06 (s, 1H), 8.60 (s, 1H), 8.55 (s, 1H), 8.16 (m, 1H), 8.06 - 7.98 (m, 4H), 7.82 (d, J = 8.4 Hz, 2H), 7.76 (t, J = 7.6 Hz, 1H), 7.71 - 7.58 (m, 3H), 7.34 (d, J = 2.0 Hz, 1H), 7.18 (d, J = 2.0 Hz, 1H), 7.12 (d, J = 2.0 Hz, 1H), 6.97 (d, J = 2.0 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.53.45 (m, 4H, underneath water peak), 3.37 - 3.35 (m, 2H), 3.26 (s, 3H), 2.62 - 2.59 (m, 2H) C 36 H 38 N 8 O 4 Calculated LRMS M / z for 646.75[M], found 647.3[M+H] +.

[0356] Ia59 6-((E)-4-Fluoro-3-methoxystyryl)-N-(1-methyl-5-((1-methyl-5-(((Z)-3-(methylamino)-3-(methylimino)propyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)nicotinamide Infrared -1 3252, 3103, 2951, 1653, 1588, 1517, 1465, 1437, 1407, 1318, 1264, 1184, 1122, 1031, 1009, 964, 800, 722 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.52 (s, 1H), 9.99 (s, 1H), 9.38 (q, J = 5.0 Hz, 1H), 9.10 (d, J = 2.3 Hz, 1H), 8.64 (q, J = 4.8 Hz, 1H), 8.34 - 8.26 (m, 2H), 7.79 (d, J = 16.0 Hz, 1H), 7.69 (d, J = 8.2 Hz, 1H), 7.59 - 7.53 (m, 1H), 7.43 (d, J = 16.1 Hz, 1H), 7.36 (d, J = 1.8 Hz, 1H), 7.27 - 7.19 (m, 2H), 7.20 (d, J = 1.9 Hz, 1H), 7.12 (d, J = 1.9 Hz, 1H), 6.95 (d, J = 1.9 Hz, 1H), 3.94 (s, 3H), 3.89 (s, 3H), 3.83 (s, 3H), 3.48 (q, J = 6.5 Hz, 2H), 3.04 (d, J = 4.9 Hz, 3H), 2.79 (d, J = 4.9 Hz, 3H), 2.73 (t, J = 6.7 Hz, 2H). C 32 H 35 FN 8 O 4 LRMS M / z calculated for 614.68[M], found 615.3[M+H] + .

[0357] Ia60 1-Methyl-4-(1-methyl-4-(4-((E)-2-(pyrimidin-5-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-N-((Z)-3-(methylamino)-3-(methylimino)propyl)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 1074.35, 1128.36, 1186.22, 1271.09, 1388.75, 1404.18, 1436.97, 1465.9, 1560.41, 1570.06, 1610.56, 1647.21, 1653, 1978.97, 2042.62, 2160.27, 2360.87, 2945.3, 3105.39, 3263.56 cm -1 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.41 (s, 1H), 9.98 (s, 1H), 9.35 (m, 1H), 9.18 (s, 1H), 8.82 (d, J = 5.2 Hz, 1H), 8.62 (m, 1H), 8.28 (m, 1H), 8.05 - 7.98 (m, 3H), 7.89 (d, J = 8.1 Hz, 2H), 7.70 - 7.65 (m, 1H), 7.46 (d, J = 16.1 Hz, 1H), 7.35 (d, J = 1.9 Hz, 1H), 7.21 (d, J = 1.8 Hz, 1H), 7.13 (d, J = 2.0 Hz, 1H), 6.96 (d, J = 1.9 Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.41 - 3.48 (m, 2H), 3.04 (d, J = 4.7 Hz, 3H), 2.79 (d, J = 4.9 Hz, 3H), 2.73 (t, J = 6.8 Hz, 2H) C 31 H 33 N 8 O 3 567.27 [M], measured value 568.4 [M+H] + Calculated value of LRMS M / z.

[0358] Ia61 N-(1-Methyl-5-((1-methyl-5-(((Z)-3-(methylamino)-3-(methylimino)propyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)-6-((E)-3-(trifluoromethyl)styryl)nicotinamide Infrared -1 3275.13, 2166.06, 1656.85, 1587.42, 1535.34, 1435.04, 1406.11, 1327.03, 1294.24, 1265.3, 1197.79, 1118.71 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.52 (s, 1H), 9.97 (s, 1H), 9.34 (m, 1H), 9.11 (s, 1H), 8.66 - 8.58 (m, 1H), 8.34 - 8.24 (m, 2H), 8.10 - 8.01 (m, 2H), 7.86 (d, 16.0 Hz, 1H), 7.75 - 7.56 (m, 4H), 7.35 (d, J = 1.9 Hz, 1H), 7.20 (d, J = 1.8 Hz, 1H), 7.11 (d, J = 1.9 Hz, 1H), 6.94 (d, J = 1.9 Hz, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.44 - 3.50 (m, 2H, water peak), 3.03 (d, J = 4.7Hz, 3H), 2.78 (d, J = 5.0Hz, 3H), 2.72 (t, J = 6.7Hz, 2H) LRMS M / z C32H33F3N8O3 634.26 [M], found 635.3 [M+H] +.

[0359] Ia62 (E)-N-(3-((2,2-difluoroethyl)amino)-3-iminopropyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide IR (cm -1 ) 3228, 1629, 1197, 1122, 719 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.36 (s, 1H), 9.96 (s, 1H), 9.77 (m, 1H), 9.42 (s, 1H), 9.27 (d, J = 2.3 Hz, 1H), 8.99 (s, 1H), 8.56 (s, 1H), 8.19 (t, J = 5.8 Hz, 1H), 8.03 - 7.99 (m, 4H), 7.84 - 7.80 (m, 2H), 7.78 - 7.74 (m, 1H), 7.69 - 7.60 (m, 3H), 7.34 (d, J = 1.8 Hz, 1H), 7.19 (d, J = 1.8 Hz, 1H), 7.12 (d, J = 2.0 Hz, 1H), 6.96 (d, J = 2.0 Hz, 1H), 6.37 - 6.05 (m, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.78 - 3.73 (m, 2H), 3.52 - 3.49 (m, 2H), 2.66 (t, J = 6.3 Hz, 2H) C 35 H 34 F 2 N 8 O 3 LRMS M / z calculated for 652.71[M], found 653.3[M+H] +.

[0360] Ia63 (E)-N-(5-((5-((3-((2,2-difluoroethyl)amino)-3-iminopropyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-6-(4-(dimethylamino)styryl)nicotinamide IR (centi -1 ) 3269, 1570, 1527, 1166, 1122, 719 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.46 (s, 1H), 9.96 (s, 1H), 9.79 - 9.76 (m, 1H), 9.42 (s, 1H), 9.04 (d, J = 2.6 Hz, 1H), 9.00 (s, 1H), 8.26 (dd, J = 8.1, 2.4 Hz, 1H), 8.19 (t, J = 5.8 Hz, 1H), 7.72 (d, J = 16.0 Hz, 1H), 7.65 (d, J = 8.2 Hz, 1H), 7.54 (d, J = 8.9 Hz, 2H), 7.34 (d, J = 2.0 Hz, 1H), 7.19 (d, J = 2.0 Hz, 1H), 7.15 - 7.08 (m, 2H), 6.95 (d, J = 1.8 Hz, 1H), 6.76 (d, J = 9.2 Hz, 2H), 6.35 - 6.09 (m, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.78 - 3.71 (m, 2H), 3.51 (q, J = 6.3 Hz, 2H), 2.98 (s, 6H), 2.66 (t, J = 6.6 Hz, 2H) C 33 H 37 F 2 N 9 O 3 LRMS M / z calculated for 645.72[M], found 646.4[M + H] + .

[0361] Ia64 4-(4-((E)-3-Fluorostyryl)benzamide)-1-methyl-N-(1-methyl-N-((Z)-3-(methylamino)-3-(methylimino)propyl)carbamoyl)-1H-pyrrol-3-yl)-1H-pyrrole-2-carboxamide IR(cm -1 ) 3253.91, 3116.97, 2953.02, 2358.94, 2331.94, 2166.06, 2050.33, 1978.97, 1651.07, 1581.63, 1523.76, 1465.90, 1435.04, 1402.25, 1267.23, 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.34 (s, 1H), 9.97 (s, 1H), 9.34 (m, 1H), 8.60 (m, 1H), 8.27 (t, J = 5.2 Hz, J = 5.8 Hz, 1H), 7.98 (d, J = 8.3 Hz, 2H), 7.75 (d, J = 8.3 Hz, 2H), 7.52 (d, J = 10.9 Hz, 1H), 7.42 - 7.50 (m, 4H), 7.34 (d, J = 1.6 Hz, 1H), 7.20 (d, J = 1.6 Hz, 1H), 7.11 - 7.18 (m, 2H), 6.95 (d, J = 1.5 Hz, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.47 (q, J = 6.5 Hz, 2H), 3.03 (d, J = 4.6 Hz, 3H), 2.79 (d, J = 5.0 Hz, 3H), 2.72 (t, J = 6.5 Hz, 2H) C 32 H 34 FN 7 O 3 Calculated LRMS M / z for 583.7[M], found 584.3[M + H] + 。

[0362] Ia65 6 - ((E) - 4 - fluorostyryl) - N - (1 - methyl - 5 - ((1 - methyl - 5 - (((Z) - 3 - (methylamino) - 3 - (methylimino)propyl)carbamoyl) - 1H - pyrrol - 3 - yl)carbamoyl) - 1H - pyrrol - 3 - yl)nicotinamide Infrared -1 3265.49, 3122.75, 2953.02, 2162.20, 2036.83, 1978.97, 1654.92, 1637.56, 1591.27, 1527.62, 1508.33, 1458.18, 1436.97, 1406.11, 1292.31, 1267.23, 1240.23, 1190.08, 1128.36 1 H NMR (500 MHz, DMSO - d 6) δ (ppm) 10.50 (s, 1H), 9.98 (s, 1H), 9.34 (m, 1H), 9.10 (d, J = 2.0 Hz, 1H), 8.61 (m, 1H), 8.26 - 8.32 (m, 2H), 7.78 (m, 3H), 7.69 (d, J = 8.2 Hz, 1H), 7.38 (d, J = 16.8 Hz, 1H), 7.35 (d, J = 1.5 Hz, 1H), 7.28 (t, J = 9 Hz, 2H), 7.20 (d, J = 1.6 Hz, 1H), 7.12 (d, J = 1.4 Hz, 1H), 6.95 (d, J = 1.5 Hz, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.3 - 35 (m, 2H, underneath water peak), 3.03 (d, J = 4.5 Hz, 3H), 2.79 (d, J = 4.5 Hz, 3H), 2.72 (t, J = 6.5 Hz, 2H) C 31 H 33 FN 8 O 3 LRMS M / z calculated for 584.7[M], found 585.3[M + H] + 。

[0363] Ib1(E)-N-(3-imino-3-(piperidin-1-yl)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3226, 1670, 1199, 839 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.97 (s, 1H), 9.27 (d, J = 1.9 Hz, 1H), 8.99 (s, 1H), 8.58 (s, 1H), 8.48 (s, 1H), 8.23 (t, J = 5.9 Hz, 1H), 8.03 - 7.00 (m, 4H), 7.82 (d, J = 8.3 Hz, 2H), 7.79 - 7.74 (m, 1H), 7.68 - 7.62 (m, 3H), 7.34 (d, J = 1.5 Hz, 1H), 7.19 (d, J = 1.5 Hz, 1H), 7.12 (d, J = 1.5 Hz, 1H), 6.96 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.68 - 3.66 (m, 2H), 3.51 - 3.50 (m, 2H), 2.80 - 2.75 (m, 2H), 1.71 - 1.58 (m, 8H) C 38 H 40 N 8 O 3 656.32[M] + Calculated LRMS M / z for, found 657.3[M + H] + HRMS m / z calculated for C 38 H 41 O 3 N 8 657.3296[M + H] + , found 657.3292[M + H] + .

[0364] Ib2(E)-4-(4-(2-(Benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((3-imino-3-(piperidin-1-yl)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide IR (centi -1 ) 3097, 1627, 1199, 798 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.97 (s, 1H), 9.00 (s, 1H), 8.49 (s, 1H), 8.24 (t, J = 5.9 Hz, 1H), 8.10 (s, 3H), 8.02 (d, J = 8.3 Hz, 2H), 7.82 (d, J = 8.3 Hz, 2H), 7.70 (d, J = 16 Hz, 1H), 7.61 (d, J = 16 Hz, 1H), 7.34 (d, J = 1.5 Hz, 1H), 7.19 (d, J = 1.5 Hz, 1H), 7.12 (d, J = 1.5 Hz, 1H), 6.96 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.67 - 3.63 (m, 2H), 3.52 - 3.49 (m, 2H), 2.79 - 2.75 (m, 2H), 1.70 - 1.56 (m, 8H) C 35 H 37 N 9 O 4 647.30[M] + Calculated LRMS M / z for, found 648.3[M+H] + HRMS m / z calculated for C 35 H 38 O 4 N 9 648.3041[M+H] + , found 648.3036[M+H] + .

[0365] Ib3(E)-N-(3-Imino-3-(4-methylpiperazin-1-yl)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide IR (centi -1 ) 2993, 1629, 1199, 835 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.53 (s, 1H), 9.32 (s, 1H), 8.92 (s, 1H), 8.67 (s, 1H), 8.28 (t, J = 6.0 Hz, 1H), 8.08 - 8.00 (m, 4H), 7.84 - 7.81 (m, 3H), 7.70 - 7.61 (m, 3H), 7.36 - 7.32 (m, 1H), 7.20 - 7.17 (m, 1H), 7.15 - 7.13 (m, 1H), 7.03 - 7.00 (m, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.83 - 3.81 (m, 2H), 3.50 - 3.43 (m, 4H), 2.89 - 2.81 (m, 5H) C 38 H 41 N 9 O 3 671.31[M] + Calculated LRMS M / z for, found 672.3[M + H] + HRMS m / z C 38 H 42 O 3 N 9 672.3405[M + H] + Calculated for, found 672.3401[M + H] + .

[0366] Ib4(E)-4-(4-(2-(Benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((3-imino-3-(4-methylpiperazin-1-yl)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3051, 1668, 1199, 837 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.52 (s, 1H), 8.94 (s, 1H), 8.28 (t, J = 5.6 Hz, 1H), 8.11 (s, 3H), 8.01 (d, J = 8.3 Hz, 2H), 7.82 (d, J = 8.3 Hz, 2H), 7.69 - 7.62 (m, 2H), 7.34 (d, J = 1.4 Hz, 1H), 7.19 (d, J = 1.4 Hz, 1H), 7.13 (d, J = 1.5 Hz, 1H), 7.01 - 6.99 (m, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.82 - 3.79 (m, 2H), 3.14 - 3.08 (m, 2H), 2.83 (s, 3H), 2.83 - 2.75 (m, 6H) (2H missing) C 35 H 38 N 10 O 4 662.31[M] + Calculated LRMS M / z for, measured value 663.3[M + H] + HRMS m / z C 35 H 39 O 4 N 10 663.3150[M + H] + Calculated for, measured value 663.3145[M + H] + .

[0367] Ib5(E)-N-(3-Imino-3-morpholinopropyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3280, 1670, 1197, 719 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.97 (s, 1H), 9.30 (d, J, = 2.1 Hz, 1H), 9.21 (s, 1H), 8.64 (s, 1H), 8.56 (s, 1H), 8.25 (t, J = 6.6 Hz, 1H), 8.05 - 7.99 (m, 4H), 7.84 - 7.81 (m, 2H), 7.75 - 7.74 (m, 1H), 7.68 - 7.63 (m, 3H), 7.35 (d, J = 1.5 Hz, 1H), 7.20 (d, J = 1.5 Hz, 1H), 7.12 (d, J = 1.5 Hz, 1H), 6.98 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.74 - 3.71 (m, 6H), 3.56 - 3.53 (m, 3H), 3.48 - 3.46 (m, 2H) C 37 H 38 N 8 O 4 658.30[M] + Calculated LRMS M / z for, measured value 659.3[M+H] + HRMS m / z C 37 H 39 O 4 N 8 659.3089[M+H] + Calculated for, measured value 659.3082[M+H] + .

[0368] Ib6(E)-4-(4-(2-(Benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((3-imino-3-morpholinopropyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3138, 1627, 1199, 798 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.97 (s, 1H), 9.23 (s, 1H), 8.65 (s, 1H), 8.25 (t, J = 6.0 Hz, 1H), 8.11 (s, 3H), 8.01 (d, J = 8.4 Hz, 2H), 7.81 (d, J = 8.4 Hz, 2H), 7.69 (d, J = 16 Hz, 1H), 7.61 (d, J = 16 Hz, 1H), 7.34 (d, J = 1.5 Hz, 1H), 7.21 - 7.19 (m, 1H), 7.12 (d, J = 1.5 Hz, 1H), 6.97 (d, J = 1.7 Hz, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.75 - 3.70 (m, 8H), 3.47 - 3.45 (m, 2H), 2.82 - 2.72 (m, 2H) C 34 H 35 N 9 O 5 649.28[M] + Calculated LRMS M / z for, found 650.3[M+H] + HRMS m / z C 34 H 36 O 5 N 9 650.2834[M+H] + Calculated, found 650.2833[M+H] + .

[0369] Ib7(E)-N-(3-Imino-3-thiomorpholinopropyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3263, 1629, 1197, 719 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.97 (s, 1H), 9.27 (d, J = 2.0 Hz, 1H), 9.22 (s, 1H), 8.66 (s, 1H), 8.57 (s, 1H), 8.24 (t, J, = 5.8 Hz, 1H), 8.05 - 7.99 (m, 5H), 7.82 (d, J = 8.6 Hz, 2H), 7.79 - 7.75 (m, 1H), 7.68 - 7.63 (m, 3H), 7.35 (d, J = 1.5 Hz, 1H), 7.20 (d, J = 1.5 Hz, 1H), 7.13 (d, J = 1.5 Hz, 1H), 6.98 (d, J = 1.5 Hz, 1H), 3.98 - 3.93 (m, 3H), 3.88 (s, 3H), 3.83 (s, 3H), 3.47 - 3.42 (m, 2H), 2.90 - 2.86 (m, 2H), 2.81 - 2.76 (m, 5H) C 37 H 38 N 8 O 3 S 674.28[M] + Calculated LRMS M / z for, measured value 675.3[M+H] + HRMS m / z C 37 H 39 O 3 N 8 S 675.2860[M+H] + Calculated for, measured 675.2861[M+H] + .

[0370] Ib8(E)-4-(4-(2-(Benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((3-imino-3-thiomorpholinopropyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3371, 1379, 1128, 950 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.97 (s, 1H), 9.23 (s, 1H), 8.67 (s, 1H), 8.24 (t, J = 6.3 Hz, 1H), 8.11 (s, 3H), 8.02 (d, J = 8.4 Hz, 2H), 7.82 (d, J = 8.4 Hz, 2H), 7.70 (d, J = 16 Hz, 1H), 7.61 (d, J = 16 Hz, 1H), 7.34 (d, J = 1.7 Hz, 1H), 7.20 7.34 (d, J = 1.7 Hz, 1H), 7.12 (d, J = 1.7 Hz, 1H), 6.97 (d, J = 1.7 Hz, 1H), 3.97 - 3.93 (m, 4H), 3.88(s, 3H), 3.83(s, 3H), 3.46 - 3.43(m, 2H), 2.89 - 2.86(m, 2H), 2.80 - 2.78(m, 4H) C 34 H 35 N 9 O 4 S 665.25[M] + Calculated LRMS M / z for, found 666.3[M + H] + HRMS m / z C 34 H 36 O 4 N 9 S 666.2605[M + H] + Calculated, found 666.2601[M + H] + 。

[0371] Ib9(E)-6-(4-(Dimethylamino)styryl)-N-(5-((5-((3-Imino-3-thiomorpholinopropyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)nicotinamide Infrared (centi -1 ) 3105, 1670, 1575, 1166, 717 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.97 (s, 1H), 9.31 (s, 1H), 9.03 (s, 1H), 8.65 (s, 1H), 8.27 - 8.21 (m, 2H), 7.71 (d, J = 16 Hz, 1H), 7.63 (d, J = 8.2 Hz, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.19 (s, 1H), 7.14 - 7.09 (m, 2H), 6.97 (s, 1H), 6.76 (d, J = 8.8 Hz, 2H), 3.97 - 3.94 (m, 4H), 3.88 (s, 3H), 3.83 (s, 3H), 3.45 - 3.43 (m, 2H), 2.98 (s, 6H), 2.89 - 2.86 (m, 2H), 2.81 - 2.77 (m, 4H) C 35 H 41 N 9 O 3 S 667.31[M] + Calculated LRMS M / z for, found 668.4[M + H] + HRMS m / z C 35 H 42 N 9 O 3 S 668.3126[M + H] + Calculated, found 668.3118[M + H] + 。

[0372] Ib10(E)-6-(4-(Dimethylamino)styryl)-N-(5-((5-((3-Imino-3-(4-methylpiperazin-1-yl)propyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)nicotinamide IR (cm -1 ) 2970, 1670, 1128, 798 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.5 (s, 1H), 9.98 (s, 1H), 9.53 (s, 1H), 9.05 - 9.03 (m, 1H), 8.94 (s, 1H), 8.31 - 8.22 (m, 2H), 7.72 (d, J = 16 Hz, 1H), 7.64 (d, J = 8.2 Hz, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.33 (s, 1H), 7.19 (s, 1H), 7.14 - 7.08 (m, 2H), 7.00 (s, 1H), 6.76 (d, J = 8.8 Hz, 2H), 3.88 (s, 3H), 3.83 (s, 3H), 3.49 - 3.42 (m, 3H), 2.98 (s, 6H), 2.87 - 2.81 (m, 5H), 2.09 - 2.07 (m, 5H) C 36 H 44 N 10 O 3 664.36[M] + Calculated LRMS M / z for, found 665.6[M + H] + HRMS m / z C 36 H 45 N 10 O 3 665.3671[M + H] + Calculated, found 665.3665[M + H] + .

[0373] Ib11(E)-6-(4-(Dimethylamino)styryl)-N-(5-((5-((3-Imino-3-morpholinopropyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)nicotinamide Infrared (centi -1 ) 3307, 1653, 1570, 1168 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.97 (s, 1H), 9.21 (s, 1H), 9.04 (s, 1H), 8.64 (s, 1H), 8.28 - 8.22 (m, 2H), 7.71 (d, J = 16 Hz, 1H), 7.63 (d, J = 8.2 Hz, 1H), 7.54 (d, J = 8.8 Hz, 2H), 7.34 (s, 1H), 7.20 (s, 1H), 7.14 - 7.09 (m, 2H), 6.97 (s, 1H), 6.76 (s, 1H), 3.88 (s, 3H), 3.83 (s, 3H), 3.76 - 3.66 (m, 8H), 3.55 - 3.53 (m, 2H), 2.98 (s, 6H), 2.81 - 2.77 (m, 2H) C 35 H 41 O 4 N 9 651.33[M] + LRMS M / z calculated for, found 652.8[M + H] + C 35 H 42 O 4 N 9 652.3354[M + H] + HRMS m / z calculated for, found 652.3349[M + H] +.

[0374] Synthesis of the "quaternary" set of compounds The compounds of this set are synthesized by the reaction of the compounds of the present invention, or compounds containing a tertiary amine, with an alkyl halide as appropriate (Scheme 6, Route A), or by the reaction of a quaternary ammonium tail group dimer as appropriate with a head group dimer as appropriate (Scheme 6, Route B).

Chemical formula

[0375] For Route A, an appropriate starting compound (0.058 mmol) is dissolved in DMF (1 mL) together with an appropriate amine (2 eq, 0.116 mmol), and 50 oIt was stirred in C for 4 to 24 hours. The reaction was returned to room temperature if no starting material remained (monitored by LCMS). After completion, the reaction product was purified by HPLC, and the fraction containing the desired compound was lyophilized (yield about 40%). For Route B, the appropriate quaternary ammonium tail group dimer (0.1 - 0.2 mmol, 1.5 equivalents) in methanol (20 mL) was treated with Pd / C (10% w / w) and hydrogenated overnight at room temperature via a balloon. Then, the reaction mixture was filtered through celite and methanol was removed by evaporation under reduced pressure. Subsequently, the obtained residue was redissolved in DMF (1.0 mL). The appropriate head group (1 equivalent) in DMF (1.0 mL) was treated with HBTU (1.5 equivalents) and DIPEA (1.5 equivalents), stirred for 30 minutes, and then mixed with the DMF solution of the amine. The reaction mixture was stirred overnight at room temperature and then directly purified by HPLC, and the appropriate fraction was lyophilized to obtain the desired compound (yield about 50%). For the compounds of the present invention exemplified below, details of the synthesis and characterization of the starting compounds (Reference 7 and Reference 3) are also provided.

[0376] Reference 7 (E)-N-(2-(dimethylamino)ethyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide F. Giordani et al, Journal of Medicinal Chemistry 2019 62 (6), 3021 - 3035, DOI: 10.1021 / acs.jmedchem.8b01847.

[0377] Reference 3 (E)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-N-(2-morpholinoethyl)-1H-pyrrole-2-carboxamide Nahoum G, 2007, supra.

[0378] Characterization Details of the compounds of the present invention containing a quaternary nitrogen atom.

[0379] Ic1(E)-N-Ethyl-N,N-dimethyl-2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethane-1-aminium Infrared (centi -1 ) 3325, 1676, 1199, 719 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 9.98 (s, 1H), 9.30 (s, 1H), 8.62 (s, 1H), 8.28 (t, J = 5.6 Hz, 1H), 8.08 - 7.99 (m, 4H), 7.85 - 7.76 (m 3H), 7.72 - 7.60 (m, 3H), 7.35 (d, J = 1.6 Hz, 1H), 7.22 (d, J = 1.6 Hz, 1H), 7.13 (d, J = 1.7 Hz, 1H), 6.99 (d, J = 1.7 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.61 - 3.55 (m, 2H), 3.45 - 3.36 (m, 4H), 3.07 (s, 6H), 1.28 (t, J = 7.2Hz, 3H) C 36 H 40 N 7 O 3 + LRMS M / z calculated for 618.32, found 618.4 [M] + HRMS M / z calculated value: C 36 H 40 N 7 O 3 618.3187, found: 618.3178 [M] + 。

[0380] Ic2(E)-N,N-dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)propane-1-aminium Infrared (centi -1) 3138, 1627, 1199, 1128 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.28 (d, J = 1.9 Hz, 1H), 8.60 (s, 1H), 8.28 (t, J = 5.6 Hz, 1H), 8.06 - 8.00 (m, 4H), 7.82 (d, J = 8.4 Hz, 2H), 7.78 (t, J = 6.9 Hz, 1H), 7.71 - 7.60 (m, 3H), 7.35 (d, J = 1.7 Hz, 1H), 7.21 (d, J = 1.7 Hz, 1H), 7.13 (d, J = 1.7 Hz, 1H) 7.00 (d, J = 1.7 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.59 (q, J = 6.1 Hz, 2H), 3.41 (t, J = 6.6 Hz, 2H), 3.32 - 3.27 (m, 2H), 3.09 (s, 6H), 1.77 - 1.68 (m, 2H) C 37 H 42 N 7 O 3 + LRMS M / z calculated for 632.33, found 632.4 [M] + C 37 H 42 N 7 O 3 HRMS M / z calculated for 632.3344, found 632.3336 [M] + Ic3(E)-N,N-dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)butan-1-aminium Infrared (centi -1 ) 3296, 1637, 1197, 719 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.27 (d, J = 2.1 Hz, 1H), 8.57 (s, 1H), 8.27 (t, J = 5.5 Hz, 1H), 8.05 - 7.99 (m, 4H), 7.82 (d, J = 8.4 Hz, 2H), 7.79 - 7.74 (m, 1H), 7.68 - 7.65 (m, 3H), 7.35 (d, J = 1.5 Hz, 1H), 7.21 (d, J = 1.5 Hz, 1H), 7.12 (d, J = 1.5 Hz, 1H), 6.99 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.61 - 3.56 (m, 2H), 3.44 - 3.40 (m, 2H), 3.36 - 3.31 (m, 2H), 3.09 (s, 6H), 1.73 - 1.65 (m, 2H), 1.35 - 1.27 (m, 2H), 0.93 (t, J = 7.3 Hz, 3H) C 38 H 44 N 7 O 3 + LRMS M / z calculated for 646.35, found 646.6 [M] + HRMS M / z calculated value: C 38 H 44 O 3 N 7 646.3500, found: 646.3496 [M] + 。

[0381] Ic4(E)-N,N-Dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)pentan-1-aminium Infrared (centi -1 ) 3288, 1639, 1197, 748 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.29 (d, J = 1.8 Hz, 1H), 8.60 (s, 1H), 8.29 (t, J = 5.7 Hz, 1H), 8.07 - 8.00 (m, 4H), 7.82 (d, J = 8.2 Hz, 2H), 7.80 - 7.76 (m, 1H), 7.71 - 7.60 (m, 3H), 7.35 (d, J = 1.4 Hz, 1H), 7.21 (d, J = 1.4 Hz, 1H), 7.12 (d, J = 1.4 Hz, 1H), 7.00 (d, J = 1.4 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.61 - 3.56(m, 2H), 3.44 - 3.40(m, 2H), 3.35 - 3.30(m, 2H), 3.09(s, 6H), 1.71 - 1.63(m, 2H), 1.34 - 1.25(m, 4H), 0.90 - 0.87(m C 39 H 46 N 7 O 3 + LRMS M / z calculated for 660.37, found 660.6 [M] + Calculated HRMS M / z: C 39 H 46 O 3 N 7 + 660.3657, found: 660.3653 [M] + 。

[0382] Ic5(E)-N,N-Dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)hexan-1-aminium Infrared (centi -1 ) 3282, 1627, 1199, 842 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.99 (s, 1H), 9.31 (s, 1H), 8.32 (s, 1H), 8.10 - 7.99 (m, 4H), 7.85 - 7.78 (m, 3H), 7.73 - 7.59 (m, 3H), 7.35 (m, 1H), 7.21 (s, 1H), 7.13 (s, 1H), 7.02 (s, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.62 - 3.55 (m, 2H), 3.45 - 3.39 (m, 2H), 3.37 - 3.30 (m, 2H), 3.10 (s, 6H), 1.74 - 1.64 (m, 2H), 1.39 - 1.25 (m, 2H), 0.86 (t, J = 6.5Hz, 3H) C 40 H 48 N 7 O 3 + LRMS M / z calculated for 674.38, found 674.4 [M] + Calculated HRMS M / z: C 40 H 48 O 3 N 7 + 674.3813, found: 674.3816 [M] + 。

[0383] Ic6(E)-N,N-Dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)heptan-1-aminium IR (centi -1 ) 3271, 1627, 1122, 719 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.27 (s, 1H), 8.58 (s, 1H), 8.27 (t, J = 5.5 Hz, 1H), 8.05 - 8.00 (m, 4H), 7.82 (d, J = 8.1 Hz, 2H), 7.79 - 7.75 (m, 1H), 7.71 - 7.60 (m, 3H), 7.36 - 7.34 (m, 1H), 7.21 - 7.20 (m, 1H), 7.13 - 7.12 (m, 1H), 7.02 - 7.00 (m, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.62 - 3.55(m, 2H), 3.44 - 3.39 (m, 2H), 3.36 - 3.30 (m, 2H), 3.08 (s, 6H), 1.73 - 1.65 (m, 2H), 1.30 - 1.22 (m, 8H), 0.86 (t, J = 7.0 Hz, 3H) C 41 H 50 N 7 O 3 + LRMS M / z calculated for 688.40, found 688.6 [M] + HRMS M / z calculated value: C 41 H 50 N 7 O 3 688.3970, found: 688.3967 [M] + .

[0384] Ic7(E)-N,N-Dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)octan-1-aminium Infrared (centi -1 ) 3298, 1641, 1197, 719 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.29 (d, J = 1.8 Hz, 1H), 8.61 (s, 1H), 8.28 (t, J = 5.5 Hz, 1H), 8.07 - 8.00 (m, 4H), 7.82 (d, J = 8.3 Hz, 2H), 7.81 - 7.76 (m, 1H), 7.71 - 7.60 (m, 3H), 7.35 - 7.34 (m, 1H), 7.22 - 7.20 (m, 1H), 7.14 - 7.11 (m, 1H), 7.02 - 7.00 (m, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.61 - 3.56 (m, 2H), 3.44 - 3.39 (m, 2H), 3.34 - 3.30 (m, 2H), 3.09 (s, 6H), 1.73 - 1.63 (m, 2H), 1.33 - 1.17 (m, 1H), 0.84 (t, J = 6.8 Hz, 3H) C 42 H 52 N 7 O 3 + LRMS M / z calculated for 702.41, found 702.5 [M] + Calculated HRMS M / z: C 42 H 52 O 3 N 7 + 702.4126, found: 702.4109 [M] + 。

[0385] Ic8(E)-N,N-Dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)nonan-1-aminium Infrared (centi -1 ) 3275, 1637, 1197, 719 1H NMR (500 MHz, DMSO-d6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.28 (d, J = 2.0 Hz, 1H), 8.61 (s, 1H), 8.28 (t, J = 5.5 Hz, 1H), 8.06 - 7.98 (m, 4H), 7.82 (d, J = 8.2 Hz, 2H), 7.80 - 7.75 (m, 1H), 7.71 - 7.60 (m, 3H), 7.34 (d, J = 1.5 Hz, 1H), 7.20 (d, J = 1.5 Hz, 1H), 7.12 (d, J = 1.5 Hz, 1H), 7.01 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.61 - 3.56 (m, 2H), 3.44 - 3.39 (m, 2H), 3.35 - 3.30 (m, 2H), 3.08 (s, 6H), 1.73 - 1.64 (m, 2H), 1.31 - 1.19 (m, 12H), 0.84 (t, J C 43 H 54 N 7 O 3 + LRMS M / z calculated for 716.43, found 716.5 [M] + C 43 H 55 O 3 N 7 + HRMS m / z calculated for 358.7178, found 358.7180 [(M + H) / 2] 2+ 。

[0386] Ic9(E)-N,N-dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)decane-1-aminium Infrared (cm -1) 3288.63, 2926.01, 1670.35, 1641.42, 1608.63, 1529.55, 1465.9, 1433.11, 1404.18, 1382.96, 1261.45, 1197.79, 1172.72, 1128.36, 1060.85, 1014.56, 1006.84, 966.34, 952.84, 894.97, 864.11, 829.39, 798.53, 771.53, 750.31, 719.45, 705.95 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.36 (s, 1H), 9.97 (s, 1H), 9.27 (d, 1H, J = 2.08 Hz), 8.56 (d, 1H), 8.27 (t, 1H, J = 5.34 Hz), 8.05 - 7.99 (m, 4H), 7.82 (d, 2H, J = 8.39 Hz), 7.76 (td, 1H, J = 7.01 Hz), 7.68 (d, 1H, J = 16.78 Hz), 7.64 (td, 1H), 7.61 (d, 1H, J = 16.42 Hz), 7.34 (d, 1H, J = 1.67 Hz), 7.20 (d, 1H, J = 1.67 Hz), 7.12 (d, 1H, J = 1.89 Hz), 7.01 (d, 1H, J = 1.67 Hz), 3.88 (s, 3H), 3.83 (s, 3H), 3.58 (q, 2H, J = 8.10 Hz), 3.41 (t, 2H, J = 8.10 Hz), 3.32 (m, 2H), 3.08 (s, 6H), 1.29 - 1.14 (m, 18H), 0.84 (t, 3H, J = 6.71 Hz) C 44 H 56 N 7 O 3 + LRMS M / z calculated for 730.44, found 730.0 [M] + 。

[0387] Ic10(E)-N,N-Dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)undecan-1-aminium Infrared (centi -1 ) 3288, 1639, 1199, 831 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.97 (s, 1H), 9.28 (d, J = 1.9 Hz, 1H), 8.58 (s, 1H), 8.28 (t, J = 5.6 Hz, 1H), 8.06 - 8.00 (m, 4H), 7.82 (d, J = 8.2 Hz, 2H), 7.80 - 7.75 (m, 1H), 7.71 - 7.59 (m, 3H), 7.35 (d, J = 1.4 Hz, 1H), 7.21 (d, J = 1.4 Hz, 1H), 7.13 (d, J = 1.4 Hz, 1H), 7.01 (d, J = 1.4 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.59 - 3.58(m, 2H), 3.44 - 3.39(m, 2H), 3.35 - 3.28(m, 2H), 3.08(s, 6H), 1.72 - 1.63(m, 2H), 1.29 - 1.19(m, 18H), 0.84(t, J = 7. C 45 H 58 N 7 O 3 + LRMS M / z calculated for 744.46, found 744.4 [M] + HRMS M / z calculated value: C 45 H 58 O 3 N 7 + 744.4596, found: 744.4596 [M] + 。

[0388] Ic11(E)-N,N-Dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)dodecan-1-aminium Infrared (cm -1 ) 3271, 2926, 2854, 1672, 1637, 1554, 1433, 1384, 1263, 1199, 1122, 1060 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.37 (s, 1H), 9.99 (s, 1H), 9.28 (d, 1H, J = 1.85 Hz), 8.58 (d, 1H, J = 1.37 Hz), 8.28 (t, 1H, J = 5.95 Hz), 8.05 (dd, 1H, J = 8.69 Hz), 8.02 (dd, 1H), 8.02 (d, 2H), 7.83 (d, 2H, J = 8.26 Hz), 7.78 (td, 1H, J = 7.47 Hz), 7.69 (d, 1H, J = 16.25 Hz), 7.66 (td, 1H), 7.63 (d, 1H, J = 16.59 Hz), 7.35 (d, 1H, J = 1.06 Hz), 7.21 (d, 1H, J = 1.09 Hz), 7.13 (d, 1H, J = 1.67 Hz), 7.02 (d, 1H, J = 1.31 Hz), 3.89 (s, 3H), 3.85 (s, 3H), 3.59 (q, 2H, J = 5.95 Hz), 3.31 (t, 2H, J = 8.08 Hz), 3.09 (s, 6H), 1.23 (m, 22H), 0.85 (t, 3H, J = 6.86 Hz) HRMS m / z C 46 H 60 N 7 O 3 + 758.4756 [M+H] + Calculated for, found 758.4752 [M+H] + .

[0389] Ic12(E)-N,N-Dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)tridecan-1-aminium Infrared (centi -1 ) 2931, 1635, 1498, 1305, 840 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm): 10.4 (s, 1H), 9.97 (s, 1H), 9.28 (s, 1H), 8.58 (s, 1H), 8.27 (t, J = 5.6 Hz, 1H), 8.08 (d, J 17 Hz, 1H), 8.06 - 8.00 (m, 4H), 7.82 (d, J = 8.3 Hz, 2H), 7.80 - 7.76 (m, 1H), 7.71 - 7.60 (m, 3H), 7.34 (d, J = 1.5 Hz, 1H), 7.20 (d, J = 1.5 Hz, 1H), 7.13 (d, J = 1.5 Hz, 1H), 7.02 (d, J = 1.5 Hz, 1H), 3.88 (s,3H), 3.84(s,3H), 3.60 - 3.56(m,2H), 3.43 - 3.50(m,2H), 3.35 - 3.29(m,2H), 3.08(s,6H), 1.74 - 1.62(m,2H), 1.28 - 1.21(m,20H), 0.84(t, J = 7.0 C 47 H 62 N 7 O 5 + LRMS M / z calculated for 772.49, found 772.5 [M] + .

[0390] Ic13(E)-N,N-Dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)tetradecan-1-aminium Infrared (centi -1 ) 2922, 1672, 1122, 719 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.30 (d, J = 2.0, 1H), 8.63 (s, 1H), 8.28 (t, J = 5.6 Hz, 1H), 8.07 - 8.00 (m, 4H), 7.87 - 7.77 (m, 3H), 7.71 - 7.60 (m, 3H), 7.35 (d, J = 1.5 Hz, 1H), 7.20 (d, J = 1.5 Hz, 1H), 7.13 (d, J = 1.5 Hz, 1H), 7.01 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.61 - 3.55 (m, 2H), 3.44 - 3.39 (m, 2H), 3.35 - 3.28 (m, 2H), 3.08 (s, 6H), 1.73 - 1.63 (m, 2H), 1.25 - 1.20 (m, 22H), 0.84 (t, J = 7.0 Hz, 3H) C 48 H 64 N 7 O 3 + HRMS M / z calculated for 786.5065, found 786.5053 [M] + .

[0391] Ic14 (E)-N,N-Dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)pentadecane-1-aminium Infrared (cm -1 ) 3286, 2924, 2852, 1670, 1637, 1558, 1433, 1406, 1263, 1199, 1124 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm): 10.37 (s, 1H), 9.99 (s, 1H), 9.28 (d, 1H, J = 1.85 Hz), 8.58 (d, 1H, J = 1.37 Hz), 8.28 (t, 1H, J = 5.95 Hz), 8.05 (dd, 1H, J = 8.69 Hz), 8.02 (dd, 1H), 8.02 (d, 2H), 7.83 (d, 2H, J = 8.26 Hz), 7.78 (td, 1H, J = 7.47 Hz), 7.69 (d, 1H, J = 16.25 Hz), 7.66 (td, 1H), 7.63 (d, 1H, J = 16.59 Hz), 7.35 (d, 1H, J = 1.06 Hz), 7.21 (d, 1H, J = 1.09 Hz), 7.13 (d, 1H, J = 1.67 Hz), 7.02 (d, 1H, J = 1.31 Hz), 3.89 (s, 3H), 3.85 (s, 3H), 3.59 (q, 2H, J = 5.95 Hz), 3.31 (t, 2H, J = 8.08 Hz), 3.09 (s, 6H), 1.23 (m, 22H), 0.85 (t, 3H, J = 6.86 Hz) HRMS m / z C 49 H 66 N 7 O 3 + 800.5222 [M+H] + Calculated for, found 800.5222 [M+H] + .

[0392] Ic15(E)-N,N-dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)hexadecane-1-aminium IR (cm -1 ) 3518, 2922, 2850, 1672, 1643, 1554, 1433, 1404, 1261, 1199, 1176, 1118 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm): 10.37 (s, 1H), 9.98 (s, 1H), 9.28 (d, 1H, J = 2.13 Hz), 8.58 (d, 1H, J = 2.27 Hz), 8.28 (t, 1H, J = 5.77 Hz), 8.04 (dd, 1H, J = 8.59 Hz), 8.02 (dd, 1H), 8.02 (d, 2H), 7.83 (d, 2H, J = 8.44 Hz), 7.77 (td, 1H, J = 8.33 Hz), 7.69 (d, 1H, J = 16.41 Hz), 7.65 (td, 1H), 7.62 (d, 1H, J = 16.31 Hz), 7.35 (d, 1H, J = 1.50 Hz), 7.21 (d, 1H, J = 1.75 Hz), 7.14 (d, 1H, J = 1.77 Hz), 7.02 (d, 1H, J = 1.79 Hz), 3.89 (s, 3H), 3.85 (s, 3H), 3.59 (q, 2H, J = 6.02 Hz), 3.32 (t, 2H), 3.09 (s, 6H), 1.23 (m, 30H), 0.85 (t, 3H, J = 6.52 Hz).

[0393] Ic16(E)-N,N-dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)heptadecan-1-aminium Infrared (centi -1 ) 2922, 1644, 1197, 1168 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.30 (s, 1H), 8.63 (s, 1H), 8.29 (t, J = 5.5 Hz, 1H), 8.08 - 8.00 (m, 4H), 7.84 - 7.77 (m, 3H), 7.72 - 7.60 (m, 3H), 7.35 (d, J = 1.5 Hz, 1H), 7.21 (d, J = 1.5 Hz, 1H), 7.13 (d, J = 1.5 Hz, 1H), 7.01 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.62 - 3.56 (m, 2H), 3.44 - 3.40 (m, 2H), 3.35 - 3.30 (m, 2H), 3.08 (s, 6H), 1.71 - 1.63 (m, 2H), 1.26 - 1.19 (m, 28H), 0.83 (t, J = 7.0 Hz, 3H) C 51 H 70 N 7 O 3 + LRMS M / z calculated for 828.55, found 828.3 [M] + Calculated HRMS M / z: C 51 H 70 N 7 O 3 + 828.5535, found: 828.5543 [M] + 。

[0394] Ic17(E)-N,N-Dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)octadecane-1-aminium Infrared (cm -1 ) 3269.34, 2929.87, 2858.51, 2160.27, 2017.54, 1978.97, 1670.35, 1637.56, 1523.76, 1436.97, 1388.75, 1265.3, 1197.79, 1172.72, 1120.64, 1060.85, 970.19, 827.46, 756.1, 719.45 1 1H NMR (500 MHz, d 6 -DMSO) δ (ppm) 10.35 (1H, s), 9.97 (1H, s), 9.25 (1H, s), 8.54 (1H, s), 8.29 - 8.26 (1H, m), 8.03 - 7.99 (5H, m), 7.83 - 7.81 (2H, m), 7.77 - 7.74 (1H, m), 7.66 - 7.63 (3H, m), 7.34 (1H, s), 7.19 (2H, s), 7.17 (1H, s), 7.12 (1H, s), 7.07 (1H, s), 7.01 (1H, s), 6.97 (1H, s), 3.88 (3H, s), 3.83 (3H, s), 3.44 - 3.40 (2H, m), 3.34 - 3.28 (2H, m), 3.08 (6H, s), 1.67 (2H, bs), 1.26 - 1.21 (32H, m), 0.85 - 0.82 (3H, m) HRMS m / z Calculated value: C 52 H 72 N 7 O 3 + 842.5691, Found: 842.5683 [M] + 。

[0395] Ic18(E)-2-(2-Methoxyethoxy)-N,N-dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)ethan-1-aminium Infrared (centi -1 ) 3298, 1637, 1116, 717 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.29 (d, J = 1.8 Hz, 1H), 8.62 (s, 1H), 8.28 (t, J = 5.7 Hz, 1H), 8.08 (d, J 17 Hz, 1H), 8.05 - 8.00 (m, 4H), 7.83 - 7.78 (m, 3H), 7.72 - 7.60 (m, 4H), 7.35 (d, J = 1.4 Hz, 1H), 7.22 (d, J = 1.4 Hz, 1H), 7.13 (d, J = 1.4 Hz, 1H), 6.99 (d, J = 1.4 Hz, 1H), 3.88 (s, 3H), 3.84 (s, 3H), 3.64 - 3.57 (m, 7H), 3.53 - 3.46 (m, 5H), 3.26 (s, 3H), 3.15 (s, 6H) C 39 H 46 N 7 O 5 + LRMS M / z calculated for 692.36, found 692.4 [M] + Calculated HRMS M / z: C 39 H 46 O 5 N 7 + 692.3555, found: 692.3555 [M] + 。

[0396] Ic19(E)-2-(2-(2-methoxyethoxy)ethoxy)-N,N-dimethyl-N-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)ethane-1- Infrared (centi -1 ) 3263, 1643, 1116, 717 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.98 (s, 1H), 9.27 (d, J = 2.0 Hz, 1H), 8.58 (s, 1H), 8.27 (t, J = 5.5 Hz, 1H), 8.06 - 7.99 (m, 4H), 7.82 (d, J = 8.1 Hz, 2H), 7.79 - 7.75 (m, 1H), 7.71 - 7.60 (m, 3H), 7.34 (d, J = 1.5 Hz, 1H), 7.21 (d, J = 1.5 Hz, 1H), 7.13 (d, J = 1.5 Hz, 1H), 6.99 (d, J = 1.5 Hz, 1H), 3.88 (s, 6H), 3.84 (s, 3H), 3.73 (t, J = 5.8 Hz, 3H), 3.64 - 3.60 (m, 5H), 3.54 - 3.50 (m, 8H), 3.45 - 3.41 (m, 5H), 3.24 (s, 3H), 3.23 (s, 3H) C 41 H 50 N 7 O 6 + LRMS M / z calculated for 736.38, found 736.4 [M] + Calculated HRMS M / z: C 41 H 50 N 7 O 6 + 736.3817, found: 736.3820 [M] + 。

[0397] Ic20(E)-N-Ethyl-N,N-dimethyl-3- (1-methyl-4-(1-methyl-4-(6-(3-(trifluoromethyl)styryl)nicotinamide))- 1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide)propan-1-aminium Infrared (cm -1) 3261.63, 3116.97, 3034.03, 2943.37, 2160.27, 1978.97, 1774.51, 1774.51, 1735.93, 1637.56, 1577.77, 1529.55, 1463.97, 1435.04, 1406.11, 1327.03, 1294.24, 1263.37, 1201.65, 1163.08, 1120.64, 1097.50, 1070.49, 1006.84 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.57 (s, 1H), 9.97 (s, 1H), 9.14 (s, 1H), 8.34 (dd, J = 6.20 Hz, J = 2.10 Hz, 1H), 8.14 (t, J = 8.80 Hz, 1H), 8.09 (s, 1H), 8.04 (d, J = 7.50 Hz, 1H), 7.91 (d, J = 15.95 Hz, 1H), 7.76 - 7.66 (m, 3H), 7.61 (d, J = 16.05 Hz, 1H), 7.36 (d, J = 1.50 Hz, 1H), 7.19 (d, J = 1.50 Hz, 1H), 7.13 (d, J = 1.50 Hz, 1H), 6.96 (d, J = 1.55 Hz, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.34 (q, J = 7.20 Hz, 2H), 3.30 - 3.24 (m, 4H), 3.00 (s, 6H), 1.94 - 1.87 (m, 2H), 1.24 (t, J = 7.05 Hz, 3H) C 34 H 39 F 3 N 7 O 3 + 650.7[M] + Calculated LRMS M / z for, found 650.3[M] + .

[0398] Ic21(E)-N-Ethyl-3-(4-(4-(6-(4-Fluoro-3-methoxystyryl)nicotinamide)-1-methyl-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxamide)-N,N-dimethylpropan-1-aminium Infrared -1 3292.49, 3105.39, 2322.29, 2166.06, 2050.33, 1978.97, 1654.92, 1637.56, 1587.42, 1514.12, 1460.11, 1436.97, 1406.11, 1261.45, 1197.79, 1120.64 1 1H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.52 (s, 1H), 9.97 (s, 1H), 9.10 (s, 1H), 8.31 (d, J = 8.1 Hz, 1H), 8.14 (s, 1H), 7.79 (d, J = 15.7 Hz, 1H), 7.69 (d, J = 7.9 Hz, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.43 (d, J = 15.9 Hz, 1H), 7.36 (s, 1H), 7.30 - 7.25 (m, 2H), 7.20 (s, 1H), 7.12 (s, 1H), 6.96 (s, 1H), 3.94 (s, 3H), 3.90 (s, 3H), 3.83 (s, 3H), 3.42 - 3.22 (m, 6H), 3.00 (s, 6H), 1.91 (s, 2H), 1.25 (t, J = 7.3 Hz, 3H). C 34 H 41 FN 7 O 4 + LCMS M / z calculated for 630.32[M], found 630.4[M] + .

[0399] Ic22(E)-3-(4-(4-(4-(2-(Benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-1-methyl-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxamide)-N-ethyl-N,N-dimethylpropan-1-aminium Infrared -13284.77, 2943.37, 2164.13, 1978.97, 1685.79, 1641.42, 1577.77, 1535.34, 1463.97, 1436.97, 1402.25, 1261.45, 1199.72, 1172.72, 1122.57, 1006.84 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.38 (s, 1H), 9.96 (s, 1H), 8.13 (m, 4H), 8.03 (d, J = 7.9 Hz, 2H), 7.83 (d, J = 8.2 Hz, 2H), 7.71 (d, J = 16.2 Hz, 1H), 7.62 (d, J = 16.6 Hz, 1H), 7.35 (s, 1H), 7.19 (s, 1H), 7.13 (s, 1H), 6.96 (s, 1H), 3.89 (s, 3H), 3.83 (s, 3H), 3.4 - 3.2 (m, 6H, underneath water peak), 3.00 (s, 6H), 1.91 (m, 2H), 1.22 (m, 3H). C 34 H 39 N 8 O 4 + 623.3 [M] + Calculated LCMS M / z for, found 623.3 [M] + .

[0400] Ic23(E)-N-Ethyl-N,N-dimethyl-3-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)propan-1-aminium Infrared -1 3284.77, 3124.68, 2162.2, 1978.97, 1637.56, 1577.77, 1560.41, 1533.41, 1508.33, 1498.69, 1465.9, 1436.97, 1404.18, 1301.95, 1259.52, 1201.65 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.35 (s, 1H), 9.94 (s, 1H), 9.26 (d, J = 2.2 Hz, 1H), 8.55 (d, J = 2.3 Hz, 1H), 8.12 (t, J = 6.0 Hz, 1H), 8.05 - 7.95 (m, 4H), 7.84 - 7.72 (m, 3H), 7.71 - 7.58 (m, 3H), 7.34 (d, J = 1.8 Hz, 1H), 7.18 (d, J = 1.9 Hz, 1H), 7.12 (d, J = 1.9 Hz, 1H), 6.95 (d, J = 1.9 Hz, 1H), 3.88 (s, 3H), 3.82 (s, 3H), 3.33 (q, J = 7.2 Hz, 2H), 3.29 - 3.23 (m, 4H), 2.98 (s, 6H), 1.93 - 1.86 (m, 2H), 1.23 (t, J = 7.1 Hz, 3H). C37H42N7O3+ 632.3 [M] + LCMS M / z calculated for, found 632.4 [M] + .

[0401] Id1 (E)-4-Hexyl-4-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)morpholin-4-ium IR (cm -1 ) 3304, 3188, 2956, 2933, 2870, 2160, 1670, 1637, 1608, 1577, 1523, 1506, 1436, 1400, 1386, 1263, 1197, 1174, 1122, 1058, 1016, 1006, 970, 956, 894, 866, 829 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.49 (s, 1H), 10.05 (s, 1H), 10.00 (s, 1H), 9.47 (s, 1H), 8.67 (d, J = 8.9 Hz, 1H), 8.50 (d, J = 8.2 Hz, 1H), 8.29 (t, J = 7.6 Hz, 2H), 8.14 - 8.09 (m, 3H), 7.91 - 7.88 (m, 3H), 7.73 (d, J = 16.7 Hz, 1H), 7.41 (s, 1H), 7.28 (s, 1H), 7.20 (s, 1H), 7.07 (s, 1H), 5.13 (t, J = 6.64 Hz, 2H), 4.07 (d, J = 10.59 Hz, 2H), 3.95 (s, 3H), 3.90 (s, 3H), 3.74 (t, J = 8.31 Hz, 3H), 3.67 - 3.58 (m, 3H), 3.25 - 3.17 (m, 2H), 2.14 - 2.04 (m, 2H), 1.58 - 1.50 (m, 2H), 1.44 - 1.29 (m, 6H), 0.95 (t, J = 6.92 Hz, 3H) C 42 H 50 N 7 O 4 + LRMS M / z calculated for 716.9, found 716.5 [M] + 。

[0402] Id2(E)-4-heptyl-4-(2-(1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamido)ethyl)morpholin-4-ium Infrared -1 3290, 2929, 2864, 2160, 1637, 1577, 1521, 1433, 1400, 1382, 1263, 1195, 1172, 1122, 1056, 1006, 974, 894, 866, 827, 798 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.42 (s, 1H), 9.99 (s, 1H), 9.93 (s, 1H), 9.40 (s, 1H), 8.61 (d, J = 9.4 Hz, 1H), 8.43 (d, J = 8.4 Hz), 8.23 (t, J = 7.3 Hz, 2H), 8.08 - 8.04 (m, 3H), 7.85 - 7.81 (m, 3H), 7.67 (d, J = 17.0 Hz, 1H), 7.35 (s, 1H), 7.21 (s, 1H), 7.14 (s, 1H), 7.02 (s, 1H), 5.07 (t, J = 8.4 Hz, 2H), 4.01 (d, J = 12.9 Hz, 2H), 3.89 (s, 3H), 3.84 (s, 3H), 3.69 - 3.64 (m, 3H), 3.30 - 3.26 (m, 2H), 3.19 - 3.10 (m, 2H), 2.07 - 2.02 (m, 2H), 1.47 - 1.44 (m, 2H), 1.37 - 1.34 (m, 2H), 1.30 - 1.26 (m, 6H), 0.87 (t, J = 6.9 Hz, 3H) C 43 H 52 N 7 O 4 + LRMS M / z calculated for 730.9, found 730.4 [M] + 。

[0403] Characterization Details of the Compounds of the Invention Containing an Amidine Group (of Formula II) II1(E) N-(5-Amino-5-iminopentyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3307, 1670, 1174, 839 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.4 (s, 1H), 9.93 (s, 1H), 9.27 (s, 1H), 8.86 (s, 2H), 8.57 (s, 1H), 8.43 (s, 2H), 8.05 - 8.01 (m, 4H), 7.82 (d, J = 8.3 Hz, 2H), 7.78 - 7.75 (m, 1H), 7.68 - 7.63 (m, 3H), 7.34 (d, J = 1.5 Hz, 1H), 7.17 (d, J = 1.6 Hz, 1H), 7.12 (d, J = 1.6 Hz, 1H), 6.92 (d, J = 1.5 Hz, 1H), 3.88 (s, 3H), 3.81 (s, 3H), 3.21 - 3.18 (m, 2H), 2.41 - 2.38 (m, 2H), 1.66 - 1.60 (m, 2H), 1.54 - 1.48 (m, 2H) C 35 H 36 O 3 N 8 616.73[M] + Calculated LRMS M / z for, found 617.8 [M + H] +.

[0404] II2 (E) N-(5-((5-((5-Amino-5-iminopentyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-6-(4-(dimethylamino)styryl)nicotinamide Infrared (centi -1 ) 3053, 1170, 1124, 719 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.45 (s, 1H), 9.93 (s, 1H), 9.03 (m, 1H), 8.86 (s, 2H), 8.42 (s, 2H), 8.28 - 8.22 (m, 1H), 8.06 - 8.03 (m, 1H), 7.71 (d, J = 15.9 Hz, 1H), 7.63 (d, J = 8.2 Hz, 1H), 7.54 (d, J = 8.9 Hz, 2H), 7.35 - 7.32 (m, 1H), 7.18 - 7.15 (m, 1H), 7.15 - 7.08 (m, 2H), 6.92 - 6.89 (m, 1H), 6.76 (d, J = 8.9 Hz, 2H), 3.88 (s, 3H), 3.81 (s, 3H), 3.21 - 3.18 (m, 2H), 2.98 (s, 6H), 2.40 - 2.37 (m, 2H), 1.65 - 1.61 (m, 2H), 1.53 - 1.48 (m, 2H) C 33 H 39 N 9 O 3 Calculated LRMS M / z for 609.74[M], found 610.3[M + H] + .

[0405] II3 (E) N-(6-Amino-6-iminohexyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3263, 1670, 1199, 719 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.35 (s, 1H), 9.92 (s, 1H), 9.29 - 9.25 (m, 1H), 8.84 (bs, 2H), 8.56 (s, 1H), 8.41 (bs, 2H), 8.04 - 8.00 (m, 5H), 7.83 - 7.74 (m, 3H), 7.68 - 7.62 (m, 3H), 7.36 - 7.32 (m, 1H), 7.18 - 7.14 (m, 1H), 7.13 - 7.10 (m, 1H), 6.92 - 6.89 (m, 1H), 3.88 (s, 3H), 3.81 (s, 3H), 3.20 - 3.17 (m, 2H), 2.36 - 2.35 (m, 2H), 1.67 - 1.60 (m, 2H), 1.55 - 1.48 (m, 2H), 1.35 - 1.30 (m, 2H) C 36 H 38 N 8 O 3 Calculated LRMS M / z for 5630.75[M], found 631.3[M + H] +.

[0406] II4 (E) N-(5-((5-((6-Amino-6-iminohexyl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-6-(4-(dimethylamino)styryl)nicotinamide Infrared (centi -1 ) 3275, 1670, 1570, 1170, 833 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.47 (s, 1H), 9.93 (s, 1H), 9.04 (s, 1H), 8.85 (s, 2H), 8.43 (s, 2H), 8.29 (d, J = 9.9 Hz, 1H), 8.00 (t, J = 5.6 Hz, 1H), 7.77 - 7.66 (m, 2H), 7.54 (d, J = 9.0 Hz, 2H), 7.36 - 7.32 (m, 1H), 7.16 - 7.10 (m, 3H), 6.91 - 6.88 (m, 1H), 6.77 (d, J = 9.0 Hz, 2H), 3.88 (s, 3H), 3.80 (s, 3H), 3.19 - 3.16 (m, 2H), 2.98 (s, 6H), 2.37 - 2.35 (m, 2H), 1.68 - 1.58 (m, 2H), 1.56 - 1.48 (m, 2H), 1.36 - 1.28 (m, 2H) C 34 H 41 N 9 O 3 LRMS M / z calculated for 623.76[M], found 624.4[M+H] + .

[0407] Synthesis of the compounds of the invention containing NH pyrrole.

[0408]

Chemical formula

[0409] Scheme 7: Synthesis of the compounds of the invention containing NH pyrrole.

[0410] The appropriate tail group dimer (0.105 mmol, 1.5 equiv) in methanol (20 mL) was treated with Pd / C (10% w / w) and hydrogenated overnight at room temperature via a balloon. The reaction mixture was then filtered through celite and the methanol was removed by evaporation under reduced pressure. The resulting residue was then redissolved in DMF (1.0 mL). The appropriate head group (0.070 mmol, 1 equiv) in DMF (1.0 mL) was treated with HBTU (40 mg, 0.105 mmol, 1.5 equiv) and DIPEA (1.5 equiv), stirred for 30 min, and then mixed with a DMF solution of the amine. The reaction mixture was stirred overnight at room temperature and then purified directly by HPLC, and the appropriate fractions were lyophilized (yield 5 - 35%).

[0411] IIIa1 (E)-N-(3-Amino-3-imino-propyl)-4-(4-(4-(2-(benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxamide Infrared -1 719, 750, 796, 833, 966, 1008, 1122, 1180, 1267, 1288, 1313, 1363, 1525, 1662, 3240 1 H NMR (500 MHz, d 6 -DMSO) δ (ppm) 11.28 (1H, s), 10.37 (1H, s) 9.95 (1H, s), 8.90 (2H, s), 8.50 (2H, s), 8.23 - 8.21 (1H, t, J = 6 Hz), 8.11 (3H, s), 8.03 - 8.02 (2H, m), 7.83 - 7.81 (2H, m), 7.72 - 7.60 (2H, m), 7.29 (1H, bs), 7.23 (1H, bs), 7.19 (1H, bs), 6.90 (1H, bs), 3.83 (3H, s), 3.53 - 3.50 (2H, m), 2.63 - 2.60 (2H, m) C 29 H 27 N 9 O 4 565.22[M] + Calculated LRMS M / z for, found 566.3[M + H] + HRMS m / z C 29 H 28 N 9 O 4 566.2259[M + H] + Calculated, found 566.2249[M + H]+ .

[0412] IIIa2(E)-N-(5-((3-Amino-3-iminopropyl)carbamoyl)-1H-pyrrol-3-yl)-1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide IR(cm -1 ) 3269, 3145, 2160, 1676, 1608, 1577, 1560, 1541, 1521, 1481, 1408, 1386, 1323, 1298, 1267, 1195, 1182, 1116, 1072, 1053, 1039, 1014, 985, 972, 862, 846, 827, 819, 800, 792, 750, 736, 719, 690, 678, 657, 651, 638, 630, 617, 607 1 H NMR (500 MHz, d 6 -DMSO) δ (ppm) 11.16 (1H, s), 10.35 (1H, s), 9.93 (1H, s), 9.26 (1H, s), 8.91 (2H, s), 8.54 (1H, s), 8.44 (2H, s), 8.22 - 8.20 (1H, t, J = 6 Hz), 8.03 - 7.97 (5H, m), 7.82 - 7.81 (2H, m), 7.77 - 7.75 (2H, m), 7.64 - 7.60 (4H, m), 7.34 (1H, s), 7.15 - 7.12 (2H, m), 7.01 (1H, bs), 3.88 (3H, s) 3.56 - 3.53 (2H, m, underneath peak water), 2.63 - 2.61(2H, m, under DMSO peak) C 32 H 30 N 8 O 3 574.24[M] + Calculated LRMS M / z for, found 575.3[M + H] + HRMS m / z C 32 H 31 O 3 N 8 575.2514[M + H] + Calculated for, found 575.2507[M + H]+ .

[0413] IIIa3(E)-N-(5-((3-Amino-3-iminopropyl)carbamoyl)-1H-pyrrol-3-yl)-4-(4-(2-(benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-1-methyl-1H-pyrrole-2-carboxamide IR (cm -1 ) 3305, 1672, 1643, 1625, 1537, 1519, 1502, 1438, 1402, 1267, 1201, 1184, 1122, 1006, 952, 837, 798, 756, 721, 688, 669, 644, 624, 609 1 1H NMR (500 MHz, d 6 -DMSO) δ (ppm) 11.16 (1H, s), 10.36, (1H, s), 9.93 (1H, s), 8.91 (2H, s), 8.45 (2H, s), 8.22 - 8.20 (1H, t, J = 6 Hz), 8.10 (3H, s), 8.02 - 8.00 (2H, m), 7.82 - 7.80 (2H, m), 7.71 - 7.59 (2H, m), 7.34 (1H, s), 7.13 - 7.12 (2H, m), 7.10 (1H, s), 3.88 (3H, s), 3.56 - 3.52 (2H, m), 2.62 - 2.60 (2H, m) C 29 H 27 N 9 O 4 565.22[M] + Calculated LRMS M / z for, found 566.3[M+H] + C 29 H 28 O 4 N 9 566.2259[M+H] + Calculated HRMS m / z for, found 566.2252[M+H] +.

[0414] IIIa4(E)-N-(3-amino-3-iminopropyl)-1-methyl-4-(4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxylic acid Infrared -1 3265, 3080, 1629, 1527, 1404, 1388, 1361, 1340, 1288, 1263, 1193, 1184, 1124, 1014, 968, 894, 833, 798, 748, 719, 688, 655, 628 1 H NMR (500 MHz, d 6 -DMSO) δ (ppm) 11.27 (1H, s), 8.58 (1H, bs), 8.52 (2H, bs), 8.22 (1H, t, J = 6 Hz), 8.04 - 8.00 (4H, m), 7.82 - 7.78 (3H, m), 7.66 - 7.63 (3H, m), 7.29 (1H, bs), 7.22 (1H, bs), 7.18 (1H, bs), 6.89 (1H, s), 3.82 (3H, s), 3.56 - 3.53 (2H, m, underneath water peak), 2.63 - 2.61 (2H, m, underneath DMSO peak) C 32 H 30 N 8 O 3 574.24[M] + Calculated LRMS M / z for, found 575.3[M + H] + HRMS m / z C 32 H 31 N 8 O 3 575.2514[M + H] + Calculated, found 575.2507[M + H] + .

[0415] IIIa5(E)-N-(5-((5-((3-amino-3-iminopropyl)carbamoyl)-1-methyl-1H-pyrrole-3-yl)carbamoyl)-1H-pyrrole-3-yl)-6-(4-(dimethylamino)styryl)nicotinamide Infrared-1 3253.91, 3035.96, 1629.85, 1525.69, 1433.11, 1365.6, 1315.45, 1284.59, 1176.58, 1124.5, 968.27, 900.76, 833.25, 798.53, 750.31, 719.45 1 H NMR (500 MHz, d 6 -DMSO) δ (ppm) 11.31 (1H, s), 10.45 (1H, s), 9.95 (1H, s), 9.04 (1H, s), 8.9 (2H, s), 8.52 (2H, s), 8.29 - 8.27 (1H, m), 8.22 (1H, t, J = Hz), 7.74 (1H, s), 7.71 (1H, s), 7.67 - 7.66 (1H, m), 7.54 - 7.53 (2H, d, J = Hz), 7.28 (1H, bs), 7.22 (1H, s), 7.16 - 7.09 (2H, m), 6.88 (1H, s), 6.76 (2H, d, J = Hz), 3.82 (3H, s), 3.52 - 3.49 (2H, m), 2.98 (6H, s), 2.63 - 2.61 (2H, m) C 30 H 33 N 9 O 3 567.27 [M] + Calculated LRMS M / z for, measured value 568.3 [M + H] + HRMS m / z C 30 H 34 O 3 N 9 568.2779 [M + H] + Calculated for, measured value 568.2771 [M + H] + 。

[0416] IIIa6(E)-N-(3-Amino-3-iminopropyl)-4-(4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared -1 719, 748, 798, 835, 964, 1124, 1190, 1290, 1398, 1629, 1670, 3248, 3332 1 1H NMR (500 MHz, d 6 -DMSO) δ (ppm) 11.30 (1H, s), 11.18 (1H, s), 10.34 (1H, s), 9.94 (1H, s), 9.27 (1H, s), 8.93 (2H, s), 8.56 - 8.53 (3H, m), 8.26 - 8.24 (1H, m), 8.04 - 8.00 (4H, m), 7.82 - 7.81 (2H, m), 7.78 - 7.74 (1H, m), 7.69 - 7.60 (3H, m), 7.28 (1H, bs), 7.20 - 7.18 (2H, m), 6.92 (1H, bs), 3.57 - 3.53 (2H, m), 2.63 - 2.60 (2H, m) C 31 H 28 N 8 O 3 560.23 [M] + Calculated LRMS M / z for, found 561.3 [M + H] + HRMS m / z C 31 H 29 O 3 N 8 561.2357 [M + H] + Calculated for, found 561.2350 [M + H] + .

[0417] IIIa7(E)-N-(5-((5-((3-Amino-3-iminopropyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1-methyl-1H-pyrrol-3-yl)-6-(4-(dimethylamino)styryl)nicotinamide Infrared -1 2980, 1660, 1631, 1564, 1529, 1436, 1369, 1321, 1286, 1255, 1180, 1168, 1151, 1124, 1064, 958, 945, 837, 796, 723 1 1H NMR (500 MHz, d 6-DMSO) δ (ppm) 11.16 (1H, s), 10.43 (1H, s), 9.93 (1H, s), 9.03 (1H, s), 8.91 (2H, s), 8.45 (2H, s), 8.24 - 8.20 (2H, m), 7.72 - 7.68 (1H, m), 7.61 - 7.60 (1H, m), 7.54 - 7.52 (2H, m), 7.33 (1H, s), 7.12 - 7.09 (3H, m), 7.00 (1H, bs), 6.76 - 6.74 (2H, m), 3.88 (3H, s), 3.56 - 3.50 (2H, m), 2.97 (6H, s), 2.63 - 2.60 (2H, m) C 30 H 33 N 9 O 3 567.27[M] + Calculated LRMS M / z for, found 568.4[M + H] + HRMS m / z C 30 H 34 O 3 N 9 568.2779[M + H] + Calculated, found 568.2780[M + H] + 。

[0418] IIIa8(E)-N-(3-Amino-3-iminopropyl)-4-(4-(4-(2-(benzofuro[3,2-c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 1670, 1610, 1591, 1519, 1404, 1263, 1201, 1184, 1126, 962, 837, 800, 746, 721 1 H NMR (500 MHz, d 6-DMSO) δ (ppm) 11.31 (1H, s), 11.19 (1H, s), 10.36 (1H, s), 9.94 (1H, s), 8.93 (2H, s), 8.54 92H, s), 8.26 (1H, t, J = 6 Hz), 8.10 (3H, s), 8.06 - 8.01 (2H, m), 7.82 - 7.80 (2H, m), 7.71 - 7.59 (2H, m), 7.28 (1H, bs), 7.21 - 7.17 (2H, m), 6.92 (1H, bs), 3.56 - 3.53 (2H, m), 2.63 - 2.61 (2H, m) C 28 H 25 N 9 O 4 551.20[M] + Calculated LRMS M / z for, found 552.0[M + H] + HRMS m / z C 29 H 26 O 4 N 9 552.2102[M + H] + Calculated, found 552.2096[M + H] + 。

[0419] IIIa9(E)-N-(5-((5-((3-Amino-3-iminopropyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)-6-(4-(dimethylamino)styryl)nicotinamide IR (cm -1 ) 3240, 1629, 1521, 1406, 1363, 1315, 1288, 1182, 1126, 1070, 945, 835, 812, 798, 750, 721 1 H NMR (500 MHz, d 6-DMSO) δ (ppm) 11.32 (1H, s), 11.18 (1H, s), 10.44 (1H, s), 9.94 (1H, s), 9.04 (1H, s), 8.92 (2H, s), 8.50 (2H, s), 8.27 - 8.23 (2H, m), 7.71 (1H, d, J = 16.0 Hz), 7.64 (1H, d, J = 8.2 Hz), 7.54 (2H, d, J = 8.8 Hz), 7.27 (1H, s), 7.49 (1H, s), 7.16 (1H, s), 7.11 (1H, d, J = 16.0 Hz), 6.91 (1H, bs), 6.76 (2H, d, J = 8.8 Hz), 3.56 - 3.52 (2H, m, under water peak), 2.97 (6H, s), 2.63 - 2.60 (2H, m) C 29 H 31 N 9 O 3 553.25[M] + Calculated LRMS M / z for, found 554.0[M + H] + HRMS m / z C 29 H 32 N 9 O 3 554.2623[M + H] + Calculated, found 554.2616[M + H] + 。

[0420] IIIb1(E)-4-(4-(2-(Benzo[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-1-methyl-N-(5-((2-morpholinoethyl)carbamoyl)-1H-pyrrol-3-yl)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3267, 1670, 1527, 1436, 1394, 1265, 1197, 1180, 1122, 831 1 H NMR (500 MHz, d 6-DMSO) δ (ppm) 11.27 (1H, s), 10.38 (1H, s), 9.98 (1H, s), 9.56 (1H, bs), 8.27 (1H, m), 8.1 (2H, s), 8.02 - 8.00 (3H, m), 7.82 - 7.80 (3H, m), 7.33 (1H, s), 7.16 - 7.13 (1H, m), 7.12 - 7.10 (1H, m), 7.04 - 7.01 (1H, bs), 4.02 - 4.00 (2H, m), 3.88 (3H, s), 3.68 - 3.63 (2H, m), 3.59 - 3.55 (4H, m), 3.33 (6H, s), 3.14 - 3.08 (4H, m) C 32 H 32 N 8 O 5 608.25[M] + Calculated LRMS M / z for, found 609.3.3[M + H] + HRMS m / z C 32 H 33 N 8 O 5 609.2568[M + H] + Calculated, found 609.2562[M + H] + .

[0421] IIIb2(E)-6-(4-(Dimethylamino)styryl)-N-(5-((1-methyl-5-((2-morpholinoethyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl IR (cm -1 ) 3253, 1666, 1641, 1529, 1438, 1402, 1288, 1197, 1182, 1124, 968, 831, 752 1 H NMR (500 MHz, d 6-DMSO) δ (ppm) 11.27 (1H, s), 10.47 (1H, s), 9.96 (1H, s), 9.04 (1H, bs), 8.37 - 8.27 (2H, m), 7.75 - 7.66 (2H, m), 7.54 - 7.53 (2H, m), 7.33 (1H, s), 7.15 - 7.10 (3H, m), 7.03 (1H, bs), 6.77 - 6.75 (2H, m), 3.99 - 3.88 (2H, m), 3.67 (3H, s), 3.59 - 3.55 (6H, m), 3.28 (2H, s), 3.10 - 3.08 (3H, m) C 33 H 38 N 8 O 4 610.30[M] + Calculated LRMS M / z for, found 611.4[M + H] + HRMS m / z C 33 H 39 N 8 O 4 611.3089[M + H] + Calculated, found 611.3083[M + H] + 。

[0422] IIIb3(E)-6-(4-(Dimethylamino)styryl)-N-(1-methyl-5-((5-((2-morpholinoethyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)nicotinamide IR (cm -1 ) 3290, 1531, 1435, 1367, 1315, 1286, 1267, 1168, 1124, 1064, 904, 831, 796, 719, 704 1 H NMR (500 MHz, d 6-DMSO) δ (ppm) 11.27 (1H, s), 10.47 (1H, s), 9.96 (1H, s), 9.04 (1H, bs), 8.37 - 8.27 (2H, m), 7.75 - 7.66 (2H, m), 7.54 - 7.53 (2H, m), 7.33 (1H, s), 7.15 - 7.10 (3H, m), 7.03 (1H, bs), 6.77 - 6.75 (2H, m), 4.02 - 3.88 (2H, m), 3.88 (3H, s), 3.72 - 3.65 (2H, m), 3.60 - 3.55 (4H, m), 3.31 - 3.28 (2H, m), 3.14 - 3.06 (2H, m), 2.96 (6H, s) C 33 H 38 N 8 O 4 610.30[M] + Calculated LRMS M / z for, found 611.4[M + H] + HRMS m / z C 33 H 39 N 8 O 4 611.3089[M + H] + Calculated, found 611.3084[M + H] + 。

[0423] IIIb4(E)-1-Methyl-N-(5-((2-morpholinoethyl)carbamoyl)-1H-pyrrol-3-yl)-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide IR (cm -1 ) 3255, 1670, 1535, 1436, 1388, 1259, 1197, 1126, 968, 833, 719 1 H NMR (500 MHz, d 6-DMSO) δ (ppm) 11.27 (1H, s), 10.35 (1H, s), 9.96 (1H, s), 9.27 (1H, s), 8.57 (1H, s), 8.29 - 8.27 (1H, m), 8.04 - 8.00 (4H, m), 7.83 - 7.81 (2H, m), 7.78 - 7.71 (1H, m), 7.66 - 7.60 (3H, m), 7.34 (1H, bs), 7.15 (1H, bs), 7.12 - 7.11 (1H, m), 7.04 (1H, bs), 4.03 - 4.00 (2H, m), 3.88 (3H, s), 3.68 - 3.63 (2H, m), 3.59 - 3.56 (4H, m), 3.31 - 3.26 (2H, m), 3.17 - 3.13 (2H, m) C 35 H 35 N 7 O 4 617.28[M] + Calculated LRMS M / z for, found 618.3[M + H] + HRMS m / z C 35 H 36 N 7 O 4 618.2323[M + H] + Calculated, found 618.2815[M + H] + 。

[0424] IIIb5(E)-N-(2-Morpholinoethyl)-4-(4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide IR (cm -1 ) 2980, 1583, 1583, 1519, 1384, 1259, 1182, 1120, 1045, 966, 952, 831, 798, 719 1 H NMR (500 MHz, d 6-DMSO) δ (ppm) 11.30 - 11.28 (2H, m), 10.34 (1H, s), 9.96 (1H, s), 9.27 (1H, s), 8.56 (1H, s), 8.31 - 8.29 (1H, m), 8.04 - 8.00 (4H, m), 7.82 - 7.80 (2H, m), 7.77 - 7.74 (1H, m), 7.69 - 7.60 (3H, m), 7.28 - 7.27 (1H, m), 7.22 - 7.19 (2H, m), 6.96 - 6.95 (1H, m), 4.02 - 4.00 (2H, m), 3.68 - 3.57 (8H, m, underneath water peak), 3.15 (2H, bs) C 34 H 33 N 7 O 4 603.26[M] + Calculated LRMS M / z for, found 604.3[M + H] + HRMS m / z C 34 H 34 O 4 N 7 604.2667[M + H] + Calculated, found 604.2658[M + H] + 。

[0425] IIIb6(E)-4-(4-(2-(Benz[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-N-(5-((2-morpholinoethyl)carbamoyl)-1H-pyrrol-3-yl)-1H-pyrrole-2-carboxamide IR(cm -1 ) 3236, 1629, 1591, 1533, 1400, 1284, 1199, 1184, 1128, 879, 831, 800, 761, 719 1 H NMR (500 MHz, d 6-DMSO) δ (ppm) 11.30 (2H, bs), 10.35 (1H, s), 9.96 (1H, s), 9.62 (1H, s), 8.30 (1H, s), 8.1 (4H, s), 8.02 - 8.01 (2H, m), 7.94 - 7.88 (1H, m), 7.82 - 7.80 (2H, m), 7.71 - 7.68 (1H, m), 7.63 - 7.59 (1H, m), 7.27 (1H, bs), 7.21 - 7.17 (2H, m), 6.95 (1H, m), 4.02 - 4.00 (2H, m), 3.68 - 3.57 (8H, m), 3.15 (2H, bs) C 31 H 30 N 8 O 5 594.23[M] + Calculated LRMS M / z for, found 595.3[M + H] + HRMS m / z C 31 H 31 O 5 N 8 595.2412[M + H] + Calculated, found 595.2403[M + H] + 。

[0426] IIIb7(E)-6-(4-(Dimethylamino)styryl)-N-(5-((5-((2-Morpholinoethyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)nicotinamide Infrared -1 1529, 1436, 1369, 1321, 1286, 1255, 1180, 1168, 1151, 1124, 1064, 958, 945, 837, 796, 723 1 H NMR (500 MHz, d 6-DMSO) δ 11.36 (1H, s), 11.29 (1H, s), 10.52 (1H, s), 9.98 (1H, s), 9.06 (1H, s), 8.39 - 8.37 (1H, m), 8.32 (1H, t, J = 5.4 Hz), 7.80 - 7.77 (2H, m), 7.57, 7.54 (2H, m), 7.28 (1H, s), 7.11 (1H, s), 7.18 - 7.15 (2H, m), 6.94 (1H, s), 6.780 - 6.77 (2H, m), 4.03 - 3.99 (2H, m), 3.66 (2H, t, J = 12Hz), 3.60 - 3.57 (4H, m), 3.30 - 3.28 (2H, m), 3.15 - 3.12 (2H, m), 2.99 (6H, s) C 32 H 36 N 8 O 4 596.29 [M] + Calculated LRMS M / z for, found 597.4 [M + H] + HRMS m / z C 32 H 37 O 4 N 8 597.2932 [M + H] + Calculated, found 597.2929 [M + H] + 。

[0427] IIIb8(E)-1-Methyl-N-(2-morpholinoethyl)-4-(4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2 Infrared -1 3253, 1670, 1643, 1583, 1529, 1438, 1402, 1286, 1265, 1195, 1178, 1120, 1055, 1016, 968, 862, 831, 798, 748, 719 1 H NMR (500 MHz, d 6-DMSO) δ (ppm) 11.28 (1H, s), 10.35 (1H, s), 9.97 (1H, s), 9.63 (1H, bs), 9.28 (1H, s), 8.59 (1H, s), 8.25 (1H, t, J = 6 Hz), 8.05 - 8.01 (4H, m), 7.82 - 7.76 (3H, m), 7.67 - 7.60 (3H, m), 7.29 (1H, bs), 7.25 (1H, bs), 7.19 (1H, bs), 6.94 (1H, s), 4.02 - 4.00 (2H, m), 3.84 (3H, s), 3.75 - 3.44 (6H, m), 3.29 - 3.27 (2H, m), 3.19 - 3.08 (2H, m) C 35 H 35 N 7 O 4 617.28[M] + Calculated LRMS M / z for, found 618.3[M + H] + HRMS m / z C 35 H 36 N 7 O 4 618.2823[M + H] + Calculated, found 618.2817[M + H] + 。

[0428] IIIb9(E)-4-(4-(4-(2-(Benz[c][1,2,5]oxadiazol-5-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1-methyl-N-(2-morpholinoethyl)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3253, 1666, 1641, 1529, 1438, 1402, 1288, 1197, 1182, 1124, 968, 831, 752 1 H NMR (500 MHz, d 6-DMSO) δ (ppm) 11.28 (1H, s), 10.36 (1H, s), 9.97 (1H, s), 9.55 (1H, bs), 8.24 (1H, bs), 8.10 (3H, s), 8.02 - 8.01 (2H, m), 7.82 - 7.80 (2H, m), 7.71 - 7.59 (2H, m), 7.28 - 7.19 (3H, m), 6.93 (1H, s), 4.03 - 4.00 (2H, m), 3.84 (3H, s), 3.68 - 3.63 (2H, m), 3.57 - 3.53 (6H, m), 3.16 - 3.13 (2H, m) C 32 H 32 N 8 O 5 608.25 [M] + LRMS M / z calculated for, found 609.3 [M + H] + C 32 H 33 N 8 O 5 609.2568 [M + H] + HRMS m / z calculated for, found 609.2560 [M + H] + Synthesis of the Compounds of the Invention of the "Amide" Set First, the "tetramer ester" is synthesized, as appropriate, via amide coupling between the head group dimer and the dimer ester. Subsequently, the "tetramer acid" is formed by hydrolysis. Finally, the compounds of the invention are formed via amide coupling of the appropriate amine "tail group" to the tetramer acid. The final amide coupling is carried out on a standard scale to obtain sufficient compound for purification and isolation from the reaction mixture and also in a nearly quantitative 96 - well plate format that can be used directly for biological evaluation without purification. The characterization items of the compounds synthesized via the 96 - well plate method are shown.

Chemical Structure

[0429] Details of the synthesis of the dimer acid ester Methyl-1-methyl-4-(1-methyl-4-nitro group-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxylate (0.300 g, 1.5 equivalents, 0.98 mmol) was added to a round-bottom flask together with palladium on carbon (0.150 g) and a stirrer. The reaction mixture was moistened with a small amount of ethyl acetate (to prevent ignition) and then dissolved in methanol. The solution was hydrogenated using hydrogen gas through a balloon and stirred for 3 h. At the same time, the appropriate head group dimer (0.65 mmol) was suspended in thionyl chloride (2 mL) and refluxed at 75 o °C for 5 h. The excess thionyl chloride was removed by evaporation under reduced pressure. The resulting acid chloride was then dissolved in DCM (5 mL). After the hydrogenation was complete, the mixture containing the newly formed amine was filtered through celite, and the methanol was removed by evaporation under reduced pressure. The amine was then dissolved in DCM (10 mL) together with triethylamine (0.41 mL, 2.16 mmol) and cooled to -20 o °C. The acid chloride solution was slowly added to the cooled amine solution. The reaction mixture was then warmed to room temperature and stirred overnight. The solvent was removed in vacuo, and then triturated in sodium bicarbonate solution to remove any excess acid. After drying, the purified product was obtained (yield ~70%).

[0430] Details of the synthesis of the dimer acid The appropriate tetramer ester (0.73 mmol) was dissolved in methanol (20 ml). NaOH (10.95 mmol, 15 eq, 0.443 mg) was dissolved in water (20 ml) and then added, and the mixture was heated to reflux (~100 °C, 3 h). The methanol removed by evaporation under reduced pressure was added dropwise to the remaining solution of HCl (1 mol) until the desired compound precipitated, and then isolated by filtration (~50% yield).

[0431] (E)-1-methyl-4-(4-(2-methyl-4-(2-methyl-4-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxylation IR (cm-1 ) 3275.13, 3207.62, 2951.09, 2922.16, 2852.72, 2158.35, 1631.78, 1606.78, 1606.7, 1566.2, 1556.55, 1504.48, 1435.04, 1386.82, 1338.6, 1278.81, 1259.52, 1201.65, 1155.36, 111, 1056.99, 1039.63, 101 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.388 (s, 1H), 9.99 (s, 1H), 9.269 (d, 1H, J = 2.39 Hz), 8.55 (d, 1H, J = 1.89 Hz), 8.04 (dd, 1H), 8.03 (d, 2H), 8.00 (dd, 1H), 7.82 (d, 2H, J = 8.67 Hz), 7.76 (td, 1H, J = 8.19 Hz), 7.68 (d, 1H, J = 17.40 Hz), 7.77 (td, 1H), 7.63 (d, 1H, J = 16.35 Hz), 7.49 (d, 1H, J = 1.72 Hz), 7.37 (d, 1H, J = 2.12 Hz), 7.14 (d, 1H, J = 2.23 Hz), 6.93 (d, 1H, J =), 3.89 (s, 3H), 3.86 (s, 3H), 3.75 (s, 3H) C 31 H 27 N 5 O 4 533.21 [M] + Calculated LRMS M / z for, found 534.3 [M+H] + .

[0432] Methyl (E)-4-(4-(6-(4-(dimethylamino)styryl)nicotinamido)-1-methyl-1H-pyrrole-2-carboxamido)-1-methyl-1H-pyrrole-2-carboxylate 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.71 (s, 1H), 10.03 (s, 1H), 9.13 (d, J = 1.93 Hz, 1H), 8.54 (d, J = 8.53 Hz, 1H), 7.95 (m, 2H), 7.57 (d, J = 8.78 Hz, 2H), 7.49 (d, J = 1.98 Hz 1H), 7.39 (d, J = 1.71 Hz, 1H), 7.23 (d, J = 16.00 Hz, 1H), 7.15 (d, J = 1.76 Hz, 1H), 6.94 (d, J = 1.93 Hz, 1H), 6.84 (d, J = 8.28 Hz, 2H), 3.89 (s, 3H), 3.29 (s, 3H), 3.71 (s, 3H), 3.02 (s, 6H). C 29 H 30 N 6 O 4 526.23 [M] + Calculated LRMS M / z for, found 527 [M+H] + .

[0433] (E) 1-Methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxylic acid IR (cm -1 ) 3255.84, 2953.02, 2922.16, 2852.72, 2588.47, 1637.56, 1633.71, 1568.13, 1537.27, 1435.04, 1384.89, 1321.24, 1253.73, 1242.16, 1203.58, 1151.50, 1111.00, 1056.99, 1035.77, 1004.91, 966.34 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) ~12.2 (br, 1H), 10.41 (s, 1H), 9.96 (d, 1H, J = 1.65 Hz), 9.29 (d, 1H), 8.20 (dd, 1H, J = 8.46 Hz), 8.16 (dd, 1H, J = 8.03 Hz), 8.05 (d, 2H, J = 8.37 Hz), 7.93 (td, 1H, J = 8.04 Hz), 7.82 (d, 2H, J = 8.146 Hz), 7.80 (td, 1H), 7.77 (d, 1H), 7.67 (d, 1H, J = 16.5 Hz), 7.44 (d, 1H, J = 2.46 Hz), 7.37 (d, 1H, J = 1.69 Hz), 7.134 (d, 1H, J = 2.08 Hz), 6.87 (d, 1H, J = 2.46 Hz), 3.89 (s, 3H), 3.840 (s, 3H). C 30 H 25 N 5 O 4 519.19 [M] + Calculated LRMS M / z for, found 520.2 [M + H] +.

[0434] (E) 4-(4-(6-(4-(Dimethylamino)styryl)nicotinamide)-1-methyl-1H-pyrrole-2-carboxamide)-1-methyl-1H-pyrrole-2-carboxylic acid Infrared (cm -1 ) 3255.84, 2953.02, 2920.23, 2852.72, 1629.85, 1570.06, 1521.84, 1436.97, 1400.32, 1363.67, 1278.81, 1261.45, 1240.23, 1205.51, 1182.36, 1122.57, 1091.71, 1058.92, 1002.98, 968.27, 945.12, 893.04, 867.97, 804.32, 781.17, 752.24, 721.38. 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.46 (s, 1H), 9.95 (s, 1H), 9.05 (d, J = 2.04 Hz, 1H), 8.25 (dd, J = 8.08 Hz, 1.93 Hz, 1H), 7.72 (d, 15.72 Hz, 1H), 7.62 (d, J = 8.29 Hz, 1H), 7.55 (d, 8.84 Hz, 2H), 7.44 (d, J = 1.85 Hz, 1H), 7.36 (d, J = 1.53 Hz, 1H), 7.12 (m, 2H), 6.87 (d, J = 1.83 Hz, 1H), 6.77 (d, J = 8.85 Hz, 2H), 3.89 (s, 3H), 3.84 (s, 3H), 2.96 (s, 6H). C 28 H 28 N 6 O 4 512.22 [M] - Calculated LRMS M / z for, found 511 [M-H] - .

[0435] Details of the synthesis of the compounds of the "amide" set

Chemical Structure

[0436] Standard procedure Appropriately, tetracarboxylic acid (0.058 mmol) was dissolved in DMF (1 mL) together with HATU (2 eq, 0.116 mmol, 43.8 mg), and DIPEA (2 eq, 20 μL, 0.116 mmol) was stirred at room temperature for 10 minutes. An appropriate amine (2 eq, 0.116 mmol) was added, and the reaction mixture was stirred at room temperature. After completion, the reaction mixture was purified by HPLC, and the fractions containing the desired compound were lyophilized.

[0437] 96-well plate method A 60 mM amine stock solution was prepared in 100 uL of DMF. The appropriate tetrameric acid was dissolved in DMF to obtain a 25 mM stock solution. HATU was dissolved in DMF to obtain a 60 mM stock solution. DIPEA was also prepared in a 60 mM stock solution in DMF. Appropriate volumes of the HATU and DIPEA stock solutions were combined to obtain a single 30 mM stock solution for both HATU and DIPEA. This solution was then combined with an appropriate volume of the tetrameric acid stock solution to obtain a solution of HATU (15 mM), DIPEA (15 mM), and tetrameric acid (12.5 mM). 80 uL of the HATU, DIPEA, and tetrameric acid solution was added to the wells of a 96-well plate. 20 uL of the amine (60 mM stock solution) was added thereto to obtain a final solution containing 10 mM tetrameric acid, 12 mM HATU, 12 mM DIPEA, and 12 mM amine. The plate containing the resulting solution was reacted by amide coupling at room temperature for 48 hours without stirring. By LCMS analysis, after 48 hours, a nearly quantitative conversion to the final product was confirmed, and a solution containing 10 mM of the appropriate compound was obtained.

[0438] Details of the characterization of the compounds of the "amide" set.

[0439] IVa1 (E)-N-(5-carbamoyl-1-methyl-1H-pyrrol-3-yl)-1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3261, 1651, 1568, 1436, 1402, 1197, 1128, 968 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.36 (s, 1H), 9.94 (s, 1H), 9.27 (d, 1H, J = 2.07 Hz), 8.56 (d, 1H, J = 1.98 Hz), 8.033 (m, 4H), 7.83 (d, 2H, J = 8.5 Hz), 7.77 (td, 1H, J = 1.35 Hz), 7.68 (d, 1H, J = 16.86 Hz), 7.65 (td, 1H), 7.64 (d, 1H, J = 16.48 Hz), 7.36 (d, 1H, J = 1.67 Hz), 7.24 (d, 1H, J = 1.67 Hz), 7.11 (d, 1H, J = 1.83 Hz), 6.87 (d, 1H, J = 1.83 Hz), 3.89 (s, 3H), 3.81 (s, 3H) N.B. The primary amide may potentially exchange and thus cannot be elucidated for the NMR spectrum C 30 H 26 N 6 O 3 LRMS M / z calculated for 518.21[M], found 519.3[M+H] + HRMS m / z C 30 H 27 N 6 O 3 Calculated for 519.2133[M+H], found 591.2139[M+H] + + .

[0440] IVa2(E)-N,1-Dimethyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3030, 1670, 1627, 1527, 1436, 1400, 1271, 1197, 1126, 970 1 1H NMR (500 MHz, DMSO-d 6 ​) δ (ppm) 10.36 (s, 1H), 9.96 (s, 1H), 9.27 (d, 1H, J = 2.07 Hz), 8.56 (d, 1H, J = 1.62 Hz), 8.033 (m, 4H), 7.94 (t, 1H, J = 4.57 Hz), 7.83 (d, 2H, J = 8.4 Hz), 7.77 (td, 1H, J = 1.06 Hz), 7.68 (d, 1H, J = 16.78 Hz), 7.65 (td, 1H), 7.62 (d, 1H, J = 16.63 Hz), 7.36 (d, 1H, J = 1.71 Hz), 7.22 (d, 1H, J = 1.70 Hz), 7.11 (d, 1H, J = 1.83 Hz), 6.83 (d, 1H, J = 1.77 Hz), 3.89 (s, 3H), 3.81 (s, 3H), 2.707 (d, 3H, J = 4.57 Hz) C 31 H 28 N 6 O 3 Calculated LRMS M / z for 532.22 [M], found 533.3 [M + H] + HRMS m / z C 31 H 29 N 6 O 3 Calculated for 533.2990 [M + H], found 533.2296 [M + H] + + .

[0441] IVa3(E)-N-(2-Cyclohexylethyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3267, 2922, 2848, 1637, 1529, 1435, 1402, 1261, 1195, 1130, 964 1 1H NMR (500 MHz, DMSO-d 6 ​) δ (ppm) 10.37 (s, 1H), 9.94 (s, 1H), 9.30 (d, 1H, J = 2.22 Hz), 8.62 (d, 1H, J = 1.83 Hz), 8.057 (dd, 1H, J = 8.69 Hz), 8.04 (dd, 1H, J = 5.64 Hz), 8.027 (d, 2H, J = 8.23 Hz), 7.96 (t, 1H, J = 5.34 Hz), 7.83 (d, 2H, J = 8.39 Hz), 7.79 (td, 1H, J = 8.23 Hz), 7.69 (d, 1H, J = 16.47 Hz), 7.67 (td, 1H), 7.63 (d, 1H, J = 16.78 Hz), 7.36 (d, 1H, J = 1.98 Hz), 7.21 (d, 1H, J = 2.13 Hz), 7.11 (d, 1H, J = 1.63 Hz), 6.86 (d, 1H, J = 1.83 Hz), 3.89 (s, 3H), 3.81 (s, 3H), 3.20 (q, 2H, J = 6.71 Hz), 1.67 (m, 8H), 1.39 (q, 2H, J = 6.86 Hz), 0.91 (m, 2H) C 38 H 40 N 6 O 3 Calculated LRMS M / z for 628.32 [M], found 629.4 [M+H] + C 38 H 41 N 6 O 3 629.3228 [M+H] + Calculated HRMS m / z for, found 629.3235 [M+H] + IVa4(E)-N-Isopropyl-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 1676, 1629, 1521, 1436, 1400, 1261, 1201, 1128 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.36 (s, 1H), 9.91 (s, 1H), 9.29 (d, 1H, J = 2.07 Hz), 8.60 (d, 1H, J = 1.59 Hz), 8.052 (dd, 1H, J = 8.39 Hz), 8.03 (dd, 1H), 8.03 (d, 2H, J = 8.39 Hz), 7.83 (d, 2H, J = 8.39 Hz), 7.78 (td, 1H, J = 1.22 Hz), 7.69 (d, 1H, J = 16.78 Hz), 7.66 (td, 1H), 7.63 (d, 1H, J = 16.48 Hz), 7.36 (d, 1H, J = 1.67 Hz), 7.16 (d, 1H, J = 1.53 Hz), 7.10 (d, 1H, J = 1.67 Hz), 6.92 (d, 1H, J = 1.52 Hz), 3.89 (s, 3H), 3.81 (s, 3H), 1.15 (s, 3H), 1.13 (s, 3H) C 33 H 32 N 6 O 3 Calculated LRMS M / z for 560.25[M], found 561.3[M+H] + HRMS m / z C 33 H 33 N 6 O 3 Calculated for 561.2603[M+H], found 561.2609[M+H] + and measured + .

[0442] IVa5(E)-N-butyl-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1) 3280.92, 2956.87, 2933.73, 2162.2, 1670.35, 1635.64, 1608.63, 1527.62, 1463.97, 1435.04, 1402.25, 1263.37, 1199.72, 1130.29, 1060.85, 1014.56, 964.41, 894.97, 831.32, 798.53, 771.53 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.36 (s, 1H), 9.94 (s, 1H), 9.28 (d, 1H, J = 2.13 Hz), 8.57 (d, 1H), 8.06 - 8.00 (m, 4H), 7.98 (t, 1H, J = 5.49 Hz), 7.83 (d, 2H, J = 8.23 hz), 7.77 (td, 1H, J = 8.10 Hz), 7.69 (d, 1H, J = 16.6 Hz), 7.65 (td, 1H), 7.63 (d, 1H, J = 16.32 Hz), 7.36 (d, 1H, J = 1.37 Hz), 7.19 (d, 1H, J = 1.83 Hz), 7.11 (d, 1H, J = 1.67 Hz), 6.87 (d, 1H, J = 1.67 Hz), 3.89 (s, 3H), 3.81 (s, 3H), 3.18 (q, 2H, J = 6.86 Hz), 1.48 (m, 2H, J = 7.01 Hz), 1.32 (m, 2H, J = 7.66 Hz), 0.91 (t, 2H, J = 7.01 Hz) C 34 H 34 N 6 O 3 LRMS M / z calculated for 574.27[M], found 575.4[M + H] +.

[0443] IVa6(E)-N-Ethyl-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (cm -1) 3155, 2960, 1633, 1435, 1259, 1184, 1087, 1014, 796 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.37 (s, 1H), 9.94 (s, 1H), 9.29 (d, 1H, J = 2.07 Hz), 8.60 (d, 1H, J = 1.37 Hz), 8.056 (dd, 1H, J = 8.39), 8.031 (dd, 1H), 8.031 (d, 2H, J = 8.39), 8.00 (t, 1H, J =), 7.83 (d, 2H, J = 8.39 Hz), 7.78 (td, 1H, J = 1.22 Hz), 7.69 (d, 1H, J = 16.78 Hz), 7.66 (td, 1H), 7.63 (d, 1H, J = 16.48 Hz), 7.36 (d, 1H, J = 1.67 Hz), 7.19 (d, 1H, J = 1.53 Hz), 7.11 (d, 1H, J = 1.67 Hz), 6.87 (d, 1H, J = 1.52 Hz), 3.89 (s, 3H), 3.82 (s, 3H), 3.49 (d, 2H, J = 11.23), 3.31 (t, 2H, J = 11.73 Hz), 3.09 (q, 2H, J = 12.35 Hz), 2.86 (s, 3H) C 32 H 30 N 6 O 3 LRMS M / z calculated for 546.24[M], found 547.3[M+H] + IVa7(E)-N-(2-(2-(2-hydroxyethoxy)ethoxy)ethyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3321, 2858, 1633, 1537, 1435, 1404, 1263, 1199, 1118, 1062 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.36 (s, 1H), 9.95 (s, 1H), 9.30 (d, 1H, J = 1.52 Hz), 8.62 (d, 1H, J = 2.28 Hz), 8.06 (dd, 1H, J = 8.39 Hz), 8.04 (dd, 1H), 8.02 (d, 2H, J = 8.23 Hz), 7.83 (d, 2H, J = 7.98 Hz), 7.79 (td, 1H, J = 8.20 Hz), 7.70 (d, 1H, J = 16.46 Hz), 7.67 (td, 1H), 7.63 (d, 1H, J = 16.51 Hz), 7.36 (d, 1H, J = 1.22 Hz), 7.22 (d, 1H), 7.11 (d, 1H), 6.88(d, 1H), 3.89(s, 3H), 3.81(s, 3H), 3.54(s, 1H), 3.50(m, 2H), 3.43(m, 6H), 3.34(q, 4H) C 36 H 38 N 6 O 6 Calculated LRMS M / z for 650.29[M], found 651.3[M+H] +.

[0444] IVa8(E)-N-(2-(2-(2-Methoxyethoxy)ethoxy)ethyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3282, 2866, 1641, 1527, 1463, 1435, 1382, 1259, 1199, 1112, 966 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.36 (s, 1H), 9.95 (s, 1H), 9.30 (d, 1H, J = 1.91 Hz), 8.02 (d, 1H, J = 2.13 Hz), 8.0 (dd, 1H, J = 8.69 Hz), 8.03 (dd, 1H), 8.02 (d, 2H, J = 8.39 Hz), 7.83 (d, 2H, J = 8.23 Hz), 7.79 (td, 1H, J = 8.23 Hz), 7.70 (d, 1H, J = 16.42 Hz), 7.67 (td, 1H), 7.63 (d, 1H, J = 16.78 Hz), 7.36 (d, 1H, J = 1.52 Hz), 7.22 (d, 1H, J = 1.95 Hz), 7.11 (d, 1H, J = 1.67 Hz), 6.88 (d, 1H, J = 2.25 Hz), 3.89 (s, 3H), 3.82 (s, 3H), 3.54 (m, 2H), 3.34 (m, 6H), 3.24 (m, 7H) C 37 H 40 N 6 O 6 Calculated LRMS M / z for 644.30[M], found 645.3[M+H] +.

[0445] IVa9(E)-N,N-bis(3-(dimethylamino)propyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (centi -1 ) 3037, 2723, 1672, 1435, 1390, 1182, 1132, 837 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.36 (s, 1H), 9.92 (s, 1H), 9.28 (d, 1H, J = 2.05 Hz), 8.56 (d, 1H, J = 1.52 Hz), 8.05 (dd, 1H, J = 8.54 Hz), 8.01 (dd, 1H), 8.01 (d, 2H, J = 8.23 Hz), 7.78 (d, 2H, J = 8.57 Hz), 7.77 (td, 1H, J = 8.64 Hz), 7.69 (d, 1H, J = 16.81 Hz), 7.65 (td, 1H), 7.62 (d, 1H, J = 16.47 Hz), 7.32 (d, 1H, J = 2.13 Hz), 7.24 (d, 1H, J = 1.54 Hz), 7.16 (d, 1H, J = 1.83 Hz), 6.61 (d, 1H, J = 1.67 Hz), 3.89 (s, 3H), 3.65 (s, 3H), 3.52 (t, 4H, J = 6.10 Hz), 3.05 (m, 4H, J = 10.07 Hz), 2.83 (s, 6H), 2.82 (s, 6H), 1.95 (m, 4H, J = 8.69 Hz) LRMS (ES + APCI) M / z C40H48N8O3 688.88 [M], found 689.4; [M+H] +.

[0446] IVa10 N-((E)-3,7-Dimethylocta-2,6-dien-1-yl)-1-methyl-4-(1-methyl-4-(4-((E)-2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3327, 1979, 1672, 1521, 1436, 1400, 1201, 1134, 837 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.37 (s, 1H), 9.95 (s, 1H), 9.28 (d, 1H, J = 2.01 Hz), 8.57 (d, 1H, J = 1.75 Hz), 8.09 (t, 1H, J = 5.52 Hz), 8.04 (dd, 1H, J = 7.02 Hz), 8.02 (dd, 1H), 8.01 (d, 2H, J = 6.77 Hz), 7.83 (d, 2H, J = 8.28 Hz), 7.76 (td, 1H, J = 6.72 Hz), 7.68 (d, 1H, J = 16.28 Hz), 7.65 (td, 1H), 7.63 (d, 1H, J = 16.70 Hz), 7.36 (d, 1H, J = 1.75 Hz), 7.20 (d, 1H, J = 1.87 Hz), 7.10 (d, 1H, J = 1.75 Hz), 6.88 (d, 1H, J = 2.00 Hz), 5.22 (t, 1H, J = 7.02 Hz), 5.10 (t, 1H, J = 7.06 Hz), 3.89 (s, 3H), 3.81 (s, 3H), 3.79 (t, 2H, J = 5.52 Hz), 2.05 (m, 2H), 1.98 (m, 2H), 1.67 (s, 3H), 1.65 (s, 3H), 1.58 (s, 3H) C 40 H 42 N 6 O 3 Calculated LRMS M / z for 654.33 [M], found 655.3; [M+H] + HRMS m / z C 40 H 43 N 6 O 3 Calculated for 655.3384 [M+H], found 655.3391 [M+H] + + .

[0447] IVa16 (E)-N,N,1-Trimethyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamido)-1H-pyrrole-2-carboxamido)-1H-pyrrole-2-carboxamide Infrared (cm -1 ​) 3278.99, 3088.03, 2160.27, 2023.33, 1978.97, 1672.28, 1643.35, 1438.90, 1394.53, 1259.52, 1199.72, 1182.36, 1128.36, 1058.92, 970.19, 831.32, 773.46, 752.24, 721.38 1 H NMR (500 MHz, DMSO-d 6 ) δ (ppm) 10.36 (s, 1H), 9.90 (s, 1H), 9.29 (d, 1H, J = 2.2 Hz,), 8.60 (s, 1H), 8.04 (m, 4H), 7.83 (d, 2H, J = 8.2 Hz), 7.78 (td, 1H, J = 1.4 Hz, 1.7Hz), 7.69 (d, 1H, J = 16.5 Hz), 7.66 (m, 1H), 7.64 (d, 1H, J = 16.9 Hz), 7.34 (d, 1H, J = 1.8 Hz), 7.26 (d, 1H, J = 1.8 Hz), 7.12 (d, 1H, J = 1.9 Hz), 6.47 (d, 1H, J = 1.8Hz), 3.89 (s, 3H), 3.66 (s, 3H), 3.06 (s, 6H). C 32 H 30 N 6 O 3 Calculated LRMS M / z for 546.63[M], found 547.3[M+H] + .

[0448] IVa17 (E) 1-Methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-N-propyl-1H-pyrrole-2-carboxamide Infrared -1 3657.04, 2980.02, 2970.38, 2887.44, 2160.27, 1977.04, 1670.35, 1637.56, 1390.68, 1197.79, 1176.58, 1122.57, 1070.49, 956.69, 833.25, 719.45, 1 H NMR (500 MHz, DMSO-d6 ) δ (ppm) 10.37 (s, 1H), 9.94 (s, 1H), 9.28 (s, 1H), 8.57 (s, 1H), 8.07 - 7.99 (m, 5H), 7.83 (d, J = 8.1 Hz, 2H), 7.77 (dd, J = 7.7, 0.7 Hz, 1H), 7.71 - 7.60 (m, 3H), 7.37 (s, 1H), 7.20 (s, 1H), 7.11 (s, 1H), 6.88 (s, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.15 (d, J = 6.3 Hz, 2H), 1.51 (q, J = 7.1 Hz, 2H), 0.89 (t, J = 7.3Hz, 3H). C 33 H 32 N 6 O 3 Calculated LRMS M / z for 560.25[M], found 561.3[M + H] + IVa18 (E) N-(2-Methoxyethyl)-1-methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-1H-pyrrole-2-carboxamide Infrared -1 3302.13, 2939.52, 1637.56, 1527.62, 1436.97, 1400.32, 1388.75, 1263.37, 1197.79, 1118.71, 829.39, 798.53, 771.53, 750.31, 719.45, 682.80, 609.51 1 H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.37 (s, 1H), 9.95 (s, 1H), 9.28 (d, J = 2.2 Hz, 1H), 8.58 (s, 1H), 8.07 - 8.00 (m, 5H), 7.83 (d, J = 8.2 Hz, 2H), 7.78 (t, J = 7.9 Hz, 1H), 7.73 - 7.60 (m, 3H), 7.37 (d, J = 1.8 Hz, 1H), 7.22 (d, J = 1.9 Hz, 1H), 7.11 (d, J = 1.8 Hz, 1H), 6.90 (d, J = 1.8 Hz, 1H), 3.89 (s, 3H), 3.82 (s, 3H), 3.43 (q, J = 5.9Hz, 2H, peak in water), 3.28 (s, 3H), 2.55 (m, 2H). C 33 H 32 N 6 O 4 LRMS M / z calculated for 576.66[M], found 577.4[M+H] + .

[0449] IVb1(E)-1-Methyl-N-(1-methyl-5-(piperidine-1-carbonyl)-1H-pyrrol-3-yl)-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 2939, 2924, 2358, 1676, 1571, 1438, 1402, 1257, 1197, 1132, 1001 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.36 (s, 1H), 9.89 (s, 1H), 9.28 (d, 1H, J = 2.07 Hz), 8.57 (d, 1H, J = 2.29 Hz), 8.05 (dd, 1H, J = 8.54 Hz), 8.025 (dd, 1H), 8.025 (d, 2H, J = 8.39 Hz), 7.83 (d, 2H, J = 8.54 Hz), 7.78 (td, 1H, J = 1.83 Hz), 7.69 (d, 1H, J = 16.43 Hz), 7.66 (td, 1H), 7.63 (d, 1H, J = 16.63 Hz), 7.34 (d, 1H, J = 1.67 Hz), 7.26 (d, 1H, J = 1.67 Hz), 7.12 (d, 1H, J = 1.76 Hz), 6.39 (d, 1H, J = 1.83 Hz), 3.89 (s, 3H), 3.63 (s, 3H), 3.59 (m, 4H), 1.65 (m, 2H), 1.54 (m, 4H) C 35 H 34 N 6 O 3 Calculated LRMS M / z for 586.27[M], found 587.7[M+H] + HRMS m / z C 35 H 35 N 6 O 3 Calculated for 587.2759[M+H], found 587.2762[M+H] + + .

[0450] IVb2(E)-1-Methyl-N-(1-methyl-5-(thiomorpholine-4-carbonyl)-1H-pyrrol-3-yl)-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3294, 2362, 2160, 1670, 1627, 1608, 1436, 1388, 1253, 1126 1 1H NMR (500 MHz, DMSO-d 6 ​) δ (ppm) 10.36 (s, 1H), 9.90 (s, 1H), 9.28 (d, 1H, J = 2.01 Hz), 8.58 (d, 1H, J = 1.52 Hz), 8.033 (m, 4H), 7.83 (d, 2H, J = 8.3 Hz), 7.77 (td, 1H, J = 1.18 Hz), 7.68 (d, 1H, J = 16.53 Hz), 7.65 (td, 1H), 7.63 (d, 1H, J = 16.41 Hz), 7.34 (d, 1H, J = 1.67 Hz), 7.29 (d, 1H, J = 1.67 Hz), 7.128 (d, 1H, J = 1.81 Hz), 6.418 (d, 1H, J = 1.54 Hz), 3.89 (s, 3H), 3.66 (m, 8H), 3.64 (s, 3H) C 34 H 32 N 6 O 3 LRMS M / z calculated for S 604.23[M], found 605.0[M+H] + C 34 H 33 N 6 O 3 S 605.2324[M+H] + HRMS m / z calculated for, found 605.2329[M+H] + IVb3(E)-N-(5-(azepane-1-carbonyl)-1-methyl-1H-pyrrol-3-yl)-1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide Infrared (cm -1 ) 3331, 2926, 1670, 1525, 1514, 1436, 1278, 1199, 1130, 970 1 1H NMR (500 MHz, DMSO-d 6) δ (ppm) 10.36 (s, 1H), 9.88 (s, 1H), 9.30 (d, 1H, J = 1.52 Hz), 8.62 (d, 1H, J = 2.28 Hz), 8.06 (dd, 1H, J = 8.39 Hz), 8.04 (dd, 1H), 8.02 (d, 2H, J = 8.23 Hz), 7.83 (d, 2H, J = 7.98 Hz), 7.80 (td, 1H, J = 8.20 Hz), 7.70 (d, 1H, J = 16.46 Hz), 7.66 (td, 1H), 7.64 (d, 1H, J = 16.51 Hz), 7.34 (d, 1H, J = 1.22 Hz), 7.26 (d, 1H), 7.12 (d, 1H), 6.42(d, 1H), 3.89(s, 3H), 3.63(s, 3H), 1.71(m, 6H), 1.56(m, 6H) C 36 H 36 N 6 O 3 Calculated LRMS M / z for 600.28[M], found 601.4[M+H] + HRMS m / z C 36 H 37 N 6 O 3 Calculated for 601.2915[M+H], found 601.2922[M+H] + Calculated, found 601.2922[M+H] + .

[0451] The following compounds were prepared by a 96-well plate strategy: ~10 mM stock solutions of these compounds were used directly for biological evaluation.

[0452] IVa11 (E)-1-Methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-N-(4-(piperidin-1-yl)butyl)-1H-pyrrole-2-carboxamide C 39 H 43 N 7 O 3 Calculated LRMS m / z for 657.34, found 658.4[M+H] + Purity based on the conversion rate from the starting material: >90%.

[0453] IVa12(E)-1-Methyl-4-(1-methyl-4-(4-(2-(quinolin-3-yl)vinyl)benzamide)-1H-pyrrole-2-carboxamide)-N-(4-(pyrrolidin-1-yl)butyl)-1H-pyrrole-2-carboxamide C 38 H 41 N 7 O 3 LRMS m / z calculated for 643.33, found 644.4 [M+H] + Purity based on the conversion rate from the starting material: >90%.

[0454] IVa13(E)-6-(4-(Dimethylamino)styryl)-N-(1-methyl-5-((1-methyl-5-(methylcarbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)nicotinamide C 29 H 31 N 7 O 3 LRMS m / z calculated for 525.25, found 526 [M+H] + Purity based on the conversion rate from the starting material: >50%.

[0455] IVa14(E)-6-(4-(Dimethylamino)styryl)-N-(1-methyl-5-((1-methyl-5-((4-(piperidin-1-yl)butyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)nicotinamide C 37 H 46 N 8 O 3 LRMS m / z calculated for 650.37, found 651 [M+H] + Purity based on the conversion rate from the starting material: >90%.

[0456] IVa15(E)-6-(4-(Dimethylamino)styryl)-N-(1-methyl-5-((1-methyl-5-((4-(pyrrolidin-1-yl)butyl)carbamoyl)-1H-pyrrol-3-yl)carbamoyl)-1H-pyrrol-3-yl)nicotinamide C 36 H 44 N 8 O 3 LRMS m / z calculated for 636.35, found 637 [M+H] + Purity based on conversion from starting material: >90%.

[0457] Anti-infective data The compounds of the present invention have been evaluated for their antibacterial, bacteriostatic, anti-parasitic and antiviral activities.

[0458] Antibacterial activity To demonstrate antibacterial activity, the compounds were evaluated against Staphylococcus aureus (ATCC 43300), Enterococcus faecalis (ATCC 51299) and Escherichia coli (ATCC 25922). The minimum inhibitory concentration (MIC, 80% inhibition) of the compounds was determined using the broth microdilution method as recommended by CLSI (Clinical and Laboratory Standards Institute, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically - 11th Edition: Approved Standard M07, 2018).

[0459] Antifungal activity To demonstrate antifungal activity, the compounds were evaluated against Calbicans (ATCC 90028), Cneoformans (F10025), Afumigatus A1160 (MFIG001), Afumigatus TR34 / L98H (F10017, azole-resistant strain), Aflavus (CBS 128.202), Rhizopus arrhizus (NEQAS12.35321), Candida auris (H.17.157), Candida glabrata (ACPF3309), Fusarium oxysporum (F7098), and Scedosporium prolificans (F2746). The minimum inhibitory concentration (MIC, 99% inhibition) of the compounds was measured using the microdilution broth method recommended by EUCAST (EUCAST Definitive Document E.DEF 9.3.2, Method for the determination of the minimal inhibitory concentration of antifungal agents in liquid media for filamentous fungi forming conidia, EUCAST Definitive Document E.DEF 7.3.2 Method for the determination of the minimal inhibitory concentration of antifungal agents in liquid media for yeasts). Four of the most active antifungal compounds were further evaluated against an expanded set of pathogenic filamentous fungi and yeast isolates available at the University of Texas Health Science Center at San Antonio (see Tables 3 and 4). The minimum inhibitory concentration (MIC, 50% inhibition) of the compounds was determined using the broth microdilution method as recommended by CLSI (M27 and M38 methodologies).

[0460] Antiparasitic activity To demonstrate antiparasitic activity, the compounds were evaluated against Tbbrucei Lister S427 (drug-sensitive wild-type), Tbbrucei B48 (strains resistant to diamidines and melaminophenylarsine), Tcongolense IL3000 (drug-sensitive wild-type), Tcongolense 6C3 (dimazen resistance strain), Tequiperdum, Tevansi, and Tvaginalis. A detailed description of the procedure for evaluating activity against Trypanosoma using the Alamar Blue (resazurin) assay is described below.

[0461] Parasites and culture Bloodstream form (BSF) T brucei s427 (see De Koning, H. Pet al., Mol. Biochem. Parasitol. 2000, 106, 181 - 185), T evansi Ant Tat 3 / 3 (see Dean, S et al., Proc. Natl. Acad. Sci. USA, 2013, 110, 14741 - 14746), and T equiperdum (see Stewart, M. Let al., Eukaryot. Cell, 2010, 9, 336 - 343) were cultured in 10% heat - inactivated fetal bovine serum (FBS (PAA Laboratories, Linz, Austria)), 14 μL / L β - mercaptoethanol (BDH, Dorset, UK), NaHCO adjusted to pH 7.4 3 (Sigma - Aldrich). These cell lines were maintained at 37 °C in a humidified 5% CO 2 atmosphere. BSF T congolense IL3000 and the clone line 6C3, which was adapted from IL3000 using diminazene aceturate (Merck) in vitro and showed approximately 10 - fold resistance, were cultured in TCBSF3 medium without erythrocytes (see Zheoat, A. Met al., 2021, Pathogens (Basel, Switzerland), 10(2), 175). To Dulbecco's minimum essential medium (MEM), 25 mM (4 - (2 - hydroxyethyl)-1 - piperazineethanesulfonic acid) (HEPES), 26 mM NaHCO 3, 5.6 mM Dd - glucose, 1 mM sodium pyruvate, 40 μM adenosine, 100 μM hypoxanthine, 16.5 μM thymidine, and 25 μM bathocuproine disulfonate disodium salt were added. To this basal medium, β - mercaptoethanol (0.0014% V / V), 1.6 mM glutamine, 100 units / mL penicillin / 0.1 mg / mL streptomycin (Gibco), 20% goat serum (Gibco), and 5% Serum Plus (SAFC Bi - sciences) were added (Coustou, V et al, 2010, PLoS Negl.Trop.Dis, 4, e618 and Giordani, F et al, JMed.Chem., 2019. BSF Tcongolense IL3000 WT and its derived strain 6C3 were cultured at 34 °C in a humidified 5% CO 2 environment.

[0462] Resazurin - based drug susceptibility assay Using a resazurin - based (Alamar blue) drug susceptibility assay, the activities of standard trypanosides in different cell lines investigated were evaluated and compared (see Gould, M.K et al, Anal.Biochem., 2008, 382, 87 - 93). Briefly, 23 - fold dilutions of the test compounds of the present invention starting at 100 μM, and a compound - free control, were prepared in 100 μL medium in a 96 - well white plate (Greiner Bio - one, Frickenhausen, Germany). Cells were seeded at 2×10 4 cells / mL for Tbbrucei and Tequiperdum, at 4×10 4 cells / mL for Tevansi, and at 5×10 5The cells were adjusted in an appropriate medium at 100 μL / mL. Then, 100 μL of the adjusted cells were added to the wells containing the drug dilutions and incubated for 48 hours under each culture condition. Subsequently, 20 μL of 125 mg / mL resazurin sodium dye was added, and the plates were incubated for an additional 24 hours. The resorufin fluorescence in each well of the plate was measured and used to calculate the half-maximal effective concentration (EC 50 ) of the drug, as described by Carruthers, L.V. et al., Mol. Microbiol., 2021, 116, 564 - 588. See A detailed description of the procedure for evaluating the activity against Trichomonas using the resorufin assay is provided by Natto M.J. et al, 2021, ACS Infect. Dis., 7:1752 - 1764...

[0463] Antiviral activity To demonstrate the antiviral activity, the compounds of the present invention were evaluated against human rhinovirus (HRV - 14), human respiratory syncytial virus (RSV A2), influenza (H1N1), and SARS - CoV - 2. The procedure for evaluating the activity against SARS - CoV - 2 is described below.

[0464] Cells and virus SARS-CoV-2 (hCoV-19 / Australia / VIC01 / 2020) was provided at P1 by The Doherty Institute, Melbourne, Australia and passaged twice in Vero / hSLAM cells [ECACC04091501]. Whole genome sequencing was performed on the passage 3 working stock using both Nanopore technology and Illumina technology, and no significant changes in the viral sequence were observed. The viral titer was determined by plaque assay in Vero E6 cells [ECACC 85020206]. Cell lines were obtained from the European Collection of Authenticated Cell Cultures (ECACC) PHE, Porton Down, UK. Cell cultures were maintained at 37 °C in minimum essential medium (MEM) (Life Technologies, California, USA) supplemented with 10% fetal bovine serum (FBS) (Sigma, Dorset, UK) and 25 mM HEPES (Life Technologies).

[0465] Plaque inhibition assay The inhibitory effects of various compounds were evaluated using the microplaque inhibition assay. Compounds were serially diluted 2-fold over a 12-step dilution range. Fixed concentrations of wild-type SARS-CoV-2 were added to the diluted compounds. Additional assay wells included virus-free controls and controls with untreated virus only. The plates (diluted compounds and virus) were then incubated at 37 °C for 1 hour to allow the compounds to neutralize the virus. The contents of the neutralization plates were then transferred to 96-well plates containing Vero-E6 cells, and the virus was allowed to adsorb to the cells at 37 °C for 1 hour. The inoculum was removed from the cell plates, and a viscous overlay (1% CMC) was added (test compounds were added to the overlay medium). The plates were then incubated for 24 hours. The cells were fixed with 8% formalin for 8 hours or more, and an immunostaining protocol was performed on the fixed cells as previously described by Bewley KR. et al. Nat. Protoc. 2021, 16(6):3114-3140. The stained foci were counted using an ELISpot counter (Cellular Technology Limited (CTL)). The counted foci data were then imported into RBioconductor. A positive control, chloroquine diphosphate (50 - 0.02 μM), was run with the test compounds on each assay plate.

[0466] Data analysis The amount (μM) of compound required to inhibit 50% (IC 50 ) of SARS-CoV-2 infectious virus foci was determined by using a midpoint probit analysis (written in the R programming language for statistical calculations and graphics) comparing to the virus-only control. All outliers were included in the midpoint probit analysis. The positive control, chloroquine diphosphate (50 - 0.02 μM), was consistent across assays with an IC 50 of 0.641 μM recorded in the 95% confidence interval of 0.448 - 0.912. The dashed lines are the 95% confidence intervals.

[0467] Activity against H1N1, HRV-14 and RSV A2 The procedure for evaluating the activity against influenza (H1N1) human rhinovirus (HRV-14) and human respiratory syncytial virus (RSV A2) is described below. The virus inhibition rate was determined by the accelerated viral neuraminidase inhibition assay (AVINA) for influenza and the viral ToxGlo assay for RSV and HRV.

[0468] Cell seeding Cells (Hep-2 for RSV A2, 15,000 cells per well; Hela Ohio for HRV-14, 20,000 cells per well; A549 for influenza H1N1, 40,000 cells per well) were seeded into white (Greiner 655098, RSV A2 assay, HRV-14 assay) or black (Greiner 655090, influenza H1N1 assay) 96-well plates in 50 μL of assay medium / well and incubated overnight at 37 °C (or 35 °C for Hela ...

Claims

1. One of the compounds of formulas I, II, III, and IV: 【Chemistry 1】 During the ceremony: Q ａ is an aryl or heteroaryl which may be substituted, and Q ｂ is an arylene or heteroarylene which may be substituted, where aryl, heteroaryl, arylene and heteroarylene are N(C １－６ alkyl) ２ , haloC １－６ alkyl, cyano, C １－６ alkyl, C １－６ alkoxy group, NH(C １－６ alkyl), NH ２ , halo and OH, and may be substituted by any one or combination selected from the group consisting of; Each R is C １－６ Alkyl, H, and halo C １－６ Independently selected from the group consisting of alkyl groups; Each R １ C １－６ Alkyl, H, and halo C １－６ Independently selected from the group consisting of alkyls, where at least one R １ H is; A is C １－６ Alkylene or Halo C １－６ It is alkylene; E is C ４－６ Alkylene or Halo C ４－６ It is alkylene; A to D are selected from the group consisting of equations Ia to Id: 【Chemistry 2】 During the ceremony: Z is O, CH ２ , N(C １－６ Selected from the group consisting of alkyl and S; each R ２ H, C １－２０ Alkyl, C １－２０ Alkoxy, C ２－２０ Alkenil, C ４－２０ Dialkenyl and C ６－２０ Independently selected from the group consisting of Trialkenil, at least one R ２ It is C, not H. １－２０ Alkyl, C １－２０ Alkoxy, C ２－２０ Alkenil, C ４－２０ Dialkenyl and C ６－２０ Trialkenyl is aryl, heterocyclyl, N(C) １－６ Alkyl) ２ Methoxy(ethoxy) １－３ , hydroxy(ethoxy) １－３ CycloC ３－８ Alkyl, Halo, Cyano, C １－６ Alkoxy, NH(C) １－６ Alkyl), NH ２ = Optionally substituted with any one or more independently selected from the group consisting of O and OH, and aryl and heterocyclyl are C １－４ Alkyl, Halo C １－４ Alkyl, C １－４ It is optionally substituted with any one or more independently selected from the group consisting of alkoxys and halos; Each R ３ is C １－２０ Alkyl, C ２－２０ Alkenil, C ４－２０ Dialkenyl and C ６－２０ Independently selected from the group consisting of trialkenyl, aryl, heterocyclyl, N(C) １－６ Alkyl) ２ Methoxy(ethoxy) １－３ , hydroxy(ethoxy) １－３ , hydroxy(ethoxy) １－３ CycloCR ３ Alkyl, Halo, Cyano, C １－２０ Alkoxy, NH(C) ２－２０ Alkyl), C ４－２０ It may be substituted with any one or more independently selected from the group consisting of ,=O and OH, where the aryl and heterocyclyl are C ６－２０ Alkyl, Halo CC １－６ Alkyl, ２ It may be substituted with any one or more independently selected from the group consisting of alkoxys and halos; R ４ is C ２－２０ Alkyl, C ２－２０ Alkenil, C ４－２０ Dialkenyl and C ６－２０ Selected from the group consisting of trialkenils, aryl, heterocyclyl, N(C) １－６ Alkyl) ２ Methoxy(ethoxy) １－３ , hydroxy(ethoxy) １－３ CycloC ３－８ Alkyl, Halo, Cyano, C １－６ Alkoxy, NH(C) １－６ Alkyl), NH ２ ,=O and OH are arbitrarily substituted with any one or more independently selected from the group consisting of these, and aryl and heterocyclyl are C １－４ Alkyl, Halo C １－４ Alkyl; A to G are selected from the group consisting of formulas IIIa and IIIb: 【Transformation 3】 and C(O)-J is one selected from the group consisting of formulas IVa and IVb: 【Chemistry 4】 During the ceremony: Each R ５ is independently selected from the group consisting of H, C １－２０ alkyl, C ２－２０ dialkenyl and C ６－２０ trialkenyl, wherein methoxy (ethoxy), N(C １－４ )amino C １－６ alkyl, C ４－２０ , N(C １－４ )amino CC ２－２０ alkyl)C ４－２０ , N(amino CC ６－２０ alkyl) １－３ , cyclo C １－３ alkyl, piperidinyl, piperazinyl, morpholinyl, aryl, halo, C １－６ alkoxy, =O and OH are independently selected from the group consisting of, and C1-20 alkyl is one or more independently selected from the group consisting of methoxy(ethoxy)1-3, hydroxy(ethoxy)1-3, di(C1-4 alkyl)amino, C1-4 alkylamino, amino, cycloC3-8 alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, aryl, halo, cyano, C1-6 alkoxy, =O, and OH. The number is arbitrarily substituted, where cycloC3-8 alkyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, 1-(3-propyl)piperidine, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, and aryl are optionally substituted with one or more independently selected from the group consisting of C1-4 alkyl, haloC1-4 alkyl, C1-4 alkoxy, and halo; and n is between 1 and 3.

2. Q ａ and Q ｂ is N(C １－４ alkyl) ２ halo C １－４ alkyl, cyano, C １－４ alkyl, C １－４ alkyl, C alkoxy group and halo, or any combination thereof, the compound according to claim 1, which may be substituted.

3. Q ａ The compound according to claim 1, which is selected from the group consisting of phenyl, quinolinyl, benzoxadiazolyl, naphthalenyl, benzothiazolyl group, isoquinolinyl, thiazolyl group, pyridinyl, pyrimidinyl, thiophenyl, pyridadinyl, phthalazinyl, imidazolyl, and pyrrolyl, which may be substituted.

4. Q ｂ The compound according to claim 1, wherein the compound is monocyclic.

5. Q ｂ The compound according to claim 1, wherein is unsubstituted.

6. Each R is independent of C １－４ The compound according to claim 1, selected from the group consisting of and H.

7. A is C １－６ The compound according to claim 1, wherein it is an alkylene.

8. Z is O, CH ２ , N (CH ３ A compound according to claim 1, selected from the group consisting of ) and S.

9. Each R ２ H, C １－９ Alkyl, C １－９ Alkoxy, C ２－９ Alkenil, C ４－９ Dialkenyl and C ６－９ Independently selected from the group consisting of Trialkenil, where C １－９ Alkyl, C １－９ Alkoxy, C ２－９ Alkenil, C ４－９ Dialkenyl and C ６－９ Trialkenyl is phenyl, 1-(C) １－６ Alkyl)piperazinyl, tetrahydropyranyl, N(C １－６ Alkyl) ２ Methoxy(ethoxy) １－３ , hydroxy(ethoxy) １－３， Thiomorphinyl, C １－３ The compound according to claim 1, which is optionally substituted with one or more independently selected from the group consisting of alkoxys and halos.

10. Each R ２ However, H, C １－９ Alkyl and C １－９ Independently selected from the group consisting of alkoxy groups, where C １－９ Alkyl and C １－９ The alkoxy group is a phenyl group, 1-(methyl)piperazinyl, tetrahydropyranyl, N(C) １－３ Alkyl) ２ , methoxy group (ethoxy) １－２ , hydroxyl group (ethoxy) １－２ The compound according to claim 1, which may be substituted with any one or more independently selected from the group consisting of thiomorphinyl, methoxy group, and fluoro.

11. Each R ３ C １－２０ Alkyl group, phenyl group, 1-(methyl)piperazinyl, tetrahydropyranyl, N(C) １－３ Alkyl) ２ Methoxy(ethoxy) １－２ , and hydroxyl group (ethoxy) １－２． The compound according to claim 1, which is optionally substituted with any one or more independently selected from the group consisting of

12. R ４ is a phenyl group, 1-(methyl)piperazinyl, tetrahydropyranyl, N(C １－３ Alkyl) ２ Methoxy(ethoxy) １－２ , and hydroxyl group (ethoxy) １－２ It may be replaced by one or more independently selected from the group consisting of C ２－２０ The compound according to claim 1, wherein it is alkyl.

13. R ４ C ２－１０ The compound according to claim 1.

14. The compound according to claim 1, wherein A-D are selected from the group consisting of formulas Ia and Ib.

15. E is C ４－６ The compound according to claim 1, wherein it is an alkylene.

16. Each R １ However, C １－４ The compound according to claim 1, independently selected from the group consisting of and H.

17. The compound according to claim 1, wherein A-G is formula IIIa.

18. Each R ５ However, H, C １－１２ Alkyl, C ２－１２ Alkenil, C ４－１２ Dialkenyl and C ６－１２ Independently selected from the group consisting of Trialkenil, where C １－１２ Alkyl is methoxy(ethoxy) １－２ , hydroxy(ethoxy) １－２ dimethylamino, methylamino, amino, chloroC ５－７ Alkyl, pyrrolidinyl, 1-(3-propyl)piperidine, 1-(3-propyl)piperazine, 4-(3-propyl)morpholine, 4-(3-propyl)thiomorpholine, aryl and C １－３ The compound according to claim 1, which may be substituted with one or more independently selected from the group consisting of alkoxys.

19. Each R ５ H, C １－１２ Alkyl and C ４－１２ Independently selected from the group consisting of dialkenyls, where C １－１２ Alkyl is methoxy(ethoxy) １－２ , hydroxyl group (ethoxy) １－２ dimethylamino, methylamino, amino, chloroC ５－７ The compound according to claim 1, which is optionally substituted with one or more elements independently selected from the group consisting of alkyl, pyrrolidinyl, 1-(3-propyl group)piperidine, and methoxy.

20. The compound according to claim 1, wherein n is 1 or 2.

21. The compound according to claim 1, which is one of the following formulas: 【Chemistry 5-1】 【Chemistry 5-2】 【Chemistry 5-3】 【Chemistry 5-4】 【Transformation 5-5】 [Transformation 5-6] [Transformation 5-7] [Transformation 5-8] 【Chemistry 5-9】 【Chemistry 5-10】 【Chemistry 5-11】 【Chemistry 5-12】 【Chemistry 5-13】 【Chemistry 5-14】 【Chemistry 5-15】 【Chemistry 5-16】 【Chemistry 5-17】 【Chemistry 5-18】 【Chemistry 5-19】 【Chemistry 5-20】 【Chemistry 5-21】 【Chemistry 5-22】 【Chemistry 5-23】 [Chemistry 5-24] 【Chemistry 5-25】 [Chemistry 5-26] 【Chemistry 5-27】 [Chemistry 5-28] [Chemistry 5-29] 【Chemistry 5-30】 【Chemistry 5-31】 【Chemistry 5-32】

22. A composition comprising one or more compounds according to any one of claims 1 to 21 and a pharmaceutically acceptable excipient.

23. The composition according to claim 22 for use as a pharmaceutical.

24. The composition according to claim 22 for use in treating any one or more conditions selected from the group consisting of viral infections, bacterial infections, fungal infections, parasitic infections and cancer.

25. A method for treating any one or more infections selected from the group consisting of viral, bacterial, fungal, and parasitic infections, and cancer, comprising administering an effective amount of the composition according to claim 22 to a patient in need thereof.

26. A composition for use according to claim 24: (i) Viral infections are caused by any one of the following: respiratory syncytial viruses, human rhinoviruses, human influenza viruses, influenza viruses, e.g., influenza A and B viruses, noroviruses, dengue viruses, yellow fever viruses, West Nile viruses, Zika viruses, Rift Valley fever viruses, African swine fever viruses, Japanese encephalitis viruses, Nipah viruses, coronaviruses, e.g., SARS-CoV-2, adenoviruses, e.g., Titisar adenovirus, herpesviruses, e.g., Macacin herpesvirus, and polyomaviruses; (ii) Bacterial infection is caused by one of the following: Staphylococcus aureus, enterococci, streptococci, Clostridium, Corynebacterium, tuberculous and non-tuberculous mycobacterium, Enterobacteriaceae, Acinetobacter baumanni, Pseudomonas aeruginosa, Helicobacter pylori, Campylobacter, Salmonella, Neisseria gonorrhoeae, Haemophilus influenzae, and Shigella; (iii) Fungal infections include Candida albicans, Candida auris, Candida parapsis, Candida crusei, Candida guilmielmondii, Cryptococcus canneoformans, Cryptococcus gattii, Aspergillus fumigatus, Aspergillus flavus, Rhizopus arghidus, Fusarium oxysporum, Fusarium solani, Skedosporium prolificans, Lomentospora prolificans, Blastomyces dermatitidis, Paecilomyces variotii, and Mucor sp. It is caused by one of the following groups: Pneumocystis jirovecii, Histoplasma capsulatum, Coccidioides immitis, and Coccidioides posadasii; (iv) Parasitic infections include Trypanosoma brucei brucei, Trypanosoma brucei gambiense, Trypanosoma brucei rhodesiense, Trypanosoma congolense, Trypanosoma equiperdum, Trypanosoma evansi, Trypanosoma cruzi, Trichomonas vaginalis, Toxoplasma gondii, Plasmodia spp, Leishmania spp, and Acanthamoeba spp. It is caused by one of the groups consisting of [the specified elements].

27. Use of the composition according to claim 22 in the binding of RNA or DNA, wherein the binding is ex vivo or in vitro.

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